A 15-day course of donepezil modulates spectral EEG dynamics related to target auditory stimuli in young, healthy adult volunteers.

OBJECTIVE: To identify possible electroencephalographic (EEG) markers of donepezil's effect on cortical activity in young, healthy adult volunteers at the group level. METHODS: Thirty subjects were administered a daily dose of either 5mg donepezil or placebo for 15days in a double-blind, randomized, cross-over trial. The electroencephalogram during an auditory oddball paradigm was recorded from 58 scalp electrodes. Current source density (CSD) transformations were applied to EEG epochs. The event-related potential (ERP), inter-trial coherence (ITC: the phase consistency of the EEG spectrum) and event-related spectral perturbation (ERSP: the EEG power spectrum relative to the baseline) were calculated for the target (oddball) stimuli. RESULTS: The donepezil and placebo conditions differed in terms of the changes in delta/theta/alpha/beta ITC and ERSP in various regions of the scalp (especially the frontal electrodes) but not in terms of latency and amplitude of the P300-ERP component. CONCLUSION: Our results suggest that ITC and ERSP analyses can provide EEG markers of donepezil's effects in young, healthy, adult volunteers at a group level. SIGNIFICANCE: Novel EEG markers could be useful to assess the therapeutic potential of drug candidates in Alzheimer's disease in healthy volunteers prior to the initiation of Phase II/III clinical studies in patients.

Mitochondria, prostate cancer, and biopsy sampling error.

Mitochondria and their associated genome are emerging as sophisticated indicators of prostate cancer biology. Alterations in the mitochondrial genome (mtgenome) have been implicated in cell proliferation, metastatic behavior, androgen independence, as a signal for apoptosis, and as a predictor of biochemical recurrence. Somatic mutation patterns in complete mtgenomes are associated with prostate specific antigen levels (PSA) in prostate cancer patients and a large-scale mtgenome deletion (3.4 kb) is consistent with a prostate "cancerization" field effect. This review will focus on the biological characteristics of mitochondria and their direct clinical application to prostate cancer. Mitochondrial science is currently influencing clinical prostate cancer diagnostics and the rapid progress in this area indicates future, break-through contributions in the general field of oncology.

Individual variation in cortisol responses to acute "on-back" restraint in an outbred hamster.

An outbred species of dwarf hamster (Phodopus campbelli) was used to assess between-individual variability in the response to, and recovery from, a one-time stressor of 6 min of physical restraint in a subordinate, on-back, position. Four repeated plasma samples were drawn under home-cage isoflurane anesthesia from 33 males and 38 females 50 min before, and then 10, 60, and 120 min after the stress onset. Plasma cortisol concentrations were higher in females than males, but there was no evidence for a sex difference in response to the stressor. The expected cross-sectional increase ( approximately 50 ng/ml) in response to the stressor, followed by recovery, was seen. However, there was extensive individual variation, ranging from no reaction to continuous decline from the initial to the final sample. Results were expressed in four ways (absolute concentration, relative concentration, and area under the curve relative to ground and relative to the stress-induced increase) and also standardized and subjected to hierarchical cluster analysis. Clusters failed to effectively partition the between-individual variation and did not cluster by sex, age, or housing conditions. The current study cautions against ignoring individual differences and suggests that outbred animal models might be particularly relevant to understanding stress-related pathological conditions.