The CD144-positive EMP exist in human plasma, and plasma CD144-EMP levels can be a clinically specific and quantitative marker of EC dysfunction and/or injury. Measurement of CD144-EMP, by providing a quantitative assessment of EC dysfunction, may be useful for identifying DM patients with increased risk of CAD.

Amyloid beta-peptide (A beta), the major constituent of the senile plaques in the brains of patients with Alzheimer's disease, is cytotoxic to neurons and has a central role in the pathogenesis of the disease. Previous studies have suggested that oxidative stress is involved in the mechanisms of A beta-induced neurotoxicity in vitro. In the present study, we examined whether oxidative stress contributes to learning and memory deficits caused by continuous intracerebroventricular infusion of A beta-(1-42). In the A beta-(1-42)-infused rats, spontaneous alternation behaviour in a Y-maze and spatial memory in a water maze task were significantly impaired, as compared with A beta-(40-1)-infused control rats. The retention of passive avoidance learning was also significantly impaired by treatment with A beta-(1-42). Potent antioxidants idebenone and alpha-tocopherol prevented the behavioural deficits in Y-maze and water maze, but not passive avoidance, tasks in A beta-(1-42)-infused rats when they were repeatedly administered by mouth once a day from 3 days before the start of A beta infusion to the end of behavioural experiments. Lipid peroxide levels in the hippocampus and cerebral cortex of A beta-(1-42)-infused rats did not differ from those in control animals, and neither idebenone nor alpha-tocopherol affected the lipid peroxide levels. These results suggest that treatment with antioxidants such as idebenone and alpha-tocopherol prevents learning and memory deficits caused by A beta.

Background: Transcranial direct-current stimulation (tDCS) is a non-invasive procedure that achieves polarity-dependent modulation of neuronal membrane potentials. It has recently been used as a functional intervention technique for the treatment of psychiatric and neurological diseases; however, its neuronal mechanisms have not been fully investigated in vivo.Objective/Hypothesis: To investigate whether the application of cathodal or anodal tDCS affects extracellular dopamine and serotonin levels in the rat striatum.Methods: Stimulation and in vivo microdialysis were carried out under urethane anesthesia, and microdialysis probes were slowly inserted into the striatum. After the collection of baseline fractions in the rat striatum, cathodal or anodal tDCS was applied continuously for 10 min with a current intensity of 800 μA from an electrode placed on the skin of the scalp. Dialysis samples were collected every 10 min until at least 400 min after the onset of stimulation.Results: Following the application of cathodal, but not anodal, tDCS for 10 min, extracellular dopamine levels increased for more than 400 min in the striatum. There were no significant changes in extracellular serotonin levels.Conclusion: These findings suggest that tDCS has a direct and/or indirect effect on the dopaminergic system in the rat basal ganglia.

1 We have previously demonstrated that continuous i.c.v. infusion of amyloid b-peptide (Ab), the major constituent of senile plaques in the brains of patients with Alzheimer's disease, results in learning and memory de®cits in rats. 2 In the present study, we investigated the e ects of ne®racetam [N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl) acetamide, DM-9384] on Ab-(1-42)-induced learning and memory de®cits in rats. 3 In the Ab-(1-42)-infused rats, spontaneous alternation behaviour in a Y-maze task, spatial reference and working memory in a water maze task, and retention of passive avoidance learning were signi®cantly impaired as compared with Ab-(40-1)-infused control rats. 4 Ne®racetam, at a dose range of 1 ± 10 mg kg 71 , improved learning and memory de®cits in the Ab-(1-42)-infused rats when it was administered p.o. 1 h before the behavioural tests. 5 Ne®racetam at a dose of 3 mg kg 71 p.o. increased the activity of choline acetyltransferase in the hippocampus of Ab-(1-42)-infused rats. 6 Ne®racetam increased dopamine turnover in the cerebral cortex and striatum of Ab-(1-42)-infused rats, but failed to a ect the noradrenaline, serotonin and 5-hydroxyindoleacetic acid content. 7 These results suggest that ne®racetam may be useful for the treatment of patients with Alzheimer's disease. Keywords: Alzheimer's disease; amyloid b-peptide; ne®racetam (DM-9384); reference memory; voltage-sensitive calcium channels; working memoryAbbreviations: 5-HIAA, 5-hydroxyindoleacetic acid; Ab, amyloid b-peptide; ACh, acetylcholine; AD, Alzheimer's disease; ANOVA, one-way analysis of variance; APP, b-amyloid precursor protein; ChAT, choline acetyltransferase; DOPAC, 3,4-dihydroxyphenylacetic acid; GABA, g-aminobutyric acid; HVA, homovanillic acid; VSCC, voltagesensitive calcium channels IntroductionAlzheimer's disease (AD) is the most common cause of progressive decline of cognitive function in aged humans. The disease is characterized neuropathologically by the presence of numerous senile plaques and neuro®brillary tangles accompanied by neuronal loss. The senile plaques are composed of amyloid b-peptide (Ab), a 40 ± 42 amino acid peptide fragment of the b-amyloid precursor protein (APP) (Kang et al., 1987). Transgenic mice, which overexpress human APP containing the mutations associated with familial AD, develop many of the pathological characterizations associated with AD (Games et al., 1995;Johnson-Wood et al., 1997; Sturchler-Pierrat et al., 1997). Furthermore, Ab is cytotoxic to neurons (Yankner et al., 1990) and renders neurons vulnerable to various insults including excitotoxicity (Koh et al., 1990;Mattson et al., 1992). These previous ®ndings suggest that Ab has a central role in the pathogenesis of AD. We have previously demonstrated that continuous infusion of Ab-(1-40) into the cerebral ventricle of rats results in learning and memory de®cits, suggesting that accumulation of Ab in the brain is related to cognitive impairments in AD . Continuous Ab-(1-40) infusion causes a decrease in choline acetyltransferase ...