P300 amplitude is insensitive to working memory load in schizophrenia.

BACKGROUND: Working memory (WM) tasks usually elicit a P300 ERP component, whose amplitude decreases with increasing WM load. So far, this effect has not been studied in schizophrenics (SZs), a group that is considered to have an aberrant brain connectivity and impairments in WM capacity. The aim of this study was to determine the dependency of the P300 component on WM load in a sample of SZ subjects. METHODS: We recorded 26 subjects (13 SZ patients and their matched controls) with an 80-channel electroencephalogram. Subjects performed an N-back task, a WM paradigm that manipulates the number of items to be stored in memory. RESULTS: In healthy subjects, P300 amplitude was highest in the low WM load condition, and lowest in both the attentional control condition and the high WM load condition. In contrast, SZs evidenced low P300 amplitude in all conditions. A significant between group difference in P300 amplitude was evidenced only at the low WM load condition (1 -back), being smaller in SZs. CONCLUSIONS: SZ subjects display a lower than normal P300 amplitude, which does not vary as a function of memory load. These results are consistent with a general impairment in WM capacity in these patients.

[Mechanisms of hypo and hyper alphalipoproteinemia in Chilean adults]. / Mecanismos de hipo e hiper alfalipoproteinemia en individuos adultos chilenos.

BACKGROUND: High density lipoprotein (HDL) cholesterol is inversely associated to atherosclerotic cardiovascular risk. Disturbances in HDL cholesterol plasma levels are frequent in the Chilean population, however the pathophysiological mechanisms are unknown. AIM: To evaluate the mechanisms involved in the hypo and hyper alfalipoproteinemias in Chilean subjects. MATERIALS AND METHODS: Twenty three subjects with hyperalphalipoproteinemia and 12 with hypoalphalipoproteinemia, paired with control subjects (col-HDL between 35 and 55 mg/dl) were studied. We measured plasma lipids, subfractions and sizing of HDL particles and enzymatic activity of cholesteryl ester transfer protein (CETP), lecithtin: cholesterol acyltransferase (LCAT), lipoprotein lipase (LPL) and hepatic lipase (LH). RESULTS: Subjects with hyperalphalipoproteinemia showed significantly higher levels of total HDL-cholesterol (70 +/- 2 vs 44 +/- 1 mg/dl), HDL 2 (30 +/- 3 vs 5 +/- 1 mg/dl), Apo A I (175 +/- 3 vs 146 +/- 4 mg/dl), lower HL activity (23.7 +/- 0.8 vs 32.4 +/- 1.8 mmol/h/l) and HDL particles of greater size, compared to their controls. Subjects with hypoalphalipoproteinemia, showed significantly lower levels of total HDL-cholesterol (26 +/- 1 vs 48 +/- 2 mg/dl), HDL 3 (21 +/- 1 vs 40 +/- 2 mg/dl), Apo A I (107 +/- 5 vs 145 +/- 7 mg/dl), lower LCAT activity (18.6 +/- 1.9 vs 26.2 +/- 1.6 nmol/h/ml) and smaller HDL particles, compared to their controls. CONCLUSION: Changes in hepatic lipase and lecithin cholesterol acyltransferase activities may explain the hyper and hypo alphalipoproteinemia respectively, in Chilean subjects.

Fibrates down-regulate hepatic scavenger receptor class B type I protein expression in mice.

Fibrates are normolipidemic drugs used in atherogenic dyslipidemia because of their ability to raise high density lipoprotein (HDL) and decrease triglyceride levels. They exert multiple effects on lipid metabolism by activating the peroxisome proliferator-activated receptor-alpha (PPAR-alpha), which controls the transcriptional regulation of genes involved in hepatic fatty acid, cholesterol, and lipoprotein metabolism. The hepatic expression of the scavenger receptor class B type I (SR-BI) plays a critical role in lipoprotein metabolism, mainly due to its ability to mediate selective cholesterol uptake. Because fibrates and PPAR-alpha agonists up-regulate SR-BI expression in human and murine macrophages, we tested whether fibrates raised a similar regulatory response on hepatic SR-BI expression in mice. Surprisingly, fibrate treatment suppressed SR-BI protein expression in the liver without changing steady state SR-BI mRNA levels. Decreased hepatic SR-BI protein expression correlated with enlarged HDL particle size. This effect was concomitant with down-regulation of CLAMP, a putative SR-BI-stabilizing protein found in the hepatic plasma membrane, which was also not associated to changes in CLAMP mRNA levels. The post-transcriptional regulatory effect of fibrates over hepatic SR-BI protein levels was dependent on PPAR-alpha expression, because it was absent in PPAR-alpha-deficient mice. Restoring hepatic SR-BI expression in fibrate-treated mice by recombinant adenoviral gene transfer abolished fibrate-mediated HDL particle size enlargement. This study describes a novel effect of fibrates on hepatic SR-BI expression providing an alternative mechanism by which this drug family modulates HDL metabolism in vivo.