Is the P300 deficit in alcoholism associated with early visual impairments (P100, N170)? An oddball paradigm

OBJECTIVE: Studies exploring chronic alcoholism with event-related potentials (ERPs) have shown delayed latency and reduced amplitude of the P300, a long-lasting positive potential reflecting decisional processing. This P300 deficit in alcoholism is generally interpreted as a disturbance in central nervous system inhibition or in memory/attention. The present study aimed at identifying if this electrophysiological deficit is already present on earlier components, and advances a new hypothesis concerning the interpretation of the P300 alteration. METHODS: Patients suffering from alcoholism and matched healthy controls had to detect, in an oddball paradigm, emotional faces among a succession of neutral faces. Behavioral performance and ERP data (recorded from 32 electrodes) were analyzed. RESULTS: In line with previous studies, data showed that alcoholism led to a P300 deficit. Moreover, we observed for the first time that this deficit begins at earlier visual (P100) and face-processing (N170) stages, and we found high positive correlations between P100, N170 and P300 for amplitude and latency values, suggesting cumulative deficits on the cognitive continuum. CONCLUSIONS: We suggest that the P300 deficit observed in chronic alcoholism could be linked to earlier visuo-spatial deficits rather than being an impairment of the specific processes linked to the P300. SIGNIFICANCE: These results call for reconsidering the interpretation of P300 impairments at a fundamental and clinical level, and shows that earlier ERP components must be taken into account in future studies.     

Neural network based tracking control of a flexible macro-micro manipulator system.

In this paper, we address the problem of stable tracking control of a flexible macro-micro manipulator (M(3)) system. A two-layer neural network is utilized to approximate the nonlinear robot dynamic behavior of the M(3) system, and the controllers for the macro and micro arms are developed without any need for prior knowledge of the dynamic model of the controlled M(3) system. A learning algorithm for the neural network using Lyapunov stability theory is derived. It is shown that both the tracking error and the weight-tuning error are uniformly ultimately bounded under this new control scheme. Simulation results are presented and compared to those obtained using a PD controller.     

The CLDN5 locus may be involved in the vulnerability to schizophrenia.

The present study was designed to detect three single nucleotide polymorphisms (SNPs) located on 22q11 that was thought as being of particularly importance for genetic research into schizophrenia. We recruited a total of 176 Chinese family trios of Han descent, consisting of mothers, fathers and affected offspring with schizophrenia for the genetic analysis. The transmission disequilibrium test (TDT) showed that of three SNPs, rs10314 in the 3'-untranslated region of the CLDN5 locus was associated with schizophrenia (chi(2) = 4.75, P = 0.029). The other two SNPs, rs1548359 present in the CDC45L locus centromeric of rs10314 and rs739371 in the 5'-flanking region of the CLDN5 locus, did not show such an association. The global chi-square (chi(2)) test showed that the 3-SNP haplotype system was not associated with schizophrenia although the 1-df test for individual haplotypes showed that the rs1548359(C)-rs10314(G)-rs739371(C) haplotype was excessively non-transmitted (chi(2) = 5.32, P = 0.02). Because the claudin proteins are a major component for barrier-forming tight junctions that could play a crucial role in response to changing natural, physiological and pathological conditions, the CLDN5 association with schizophrenia may be an important clue leading to look into a meeting point of genetic and environmental factors.     

Evidence of melanogenesis in porcine retinal pigment epithelial cells in vitro

Several weeks after porcine retinal pigment epithelial (RPE) cell cultures attain confluence, macroscopically visible brown foci appear. The cuboidal cells that form the foci contain numerous phase dark granules that do not exhibit the autofluorescence characteristic of lipofuscin. The data described here indicate that the granules are melanosomes. Electron microscopy revealed three types of electron-dense granules in these cells: simple spheres 0.3-0.5 microns in diameter, large spheres 1-2 microns in diameter, and lysosomal aggregations of the smaller spheres. The matrix of both spheres is composed of 40-nm microvesicles that were also found free in the cytoplasm and aggregated within vacuolar structures. Reversed-phase high-performance liquid chromatography of RPE cells and their media detected melanogens, i.e. intermediates of melanin biosynthesis, including several indole derivatives. The porcine RPE cultures therefore may be a useful system for studying melanogenic regulation.     

NADPH-Diaphorase-Positive Neurons in Primate Cerebral Cortex Colocalize with GABA and Calcium-Binding Proteins

Neurons in the monkey cerebral cortex containing nicotinamideadenine dinucleotide phosphate-diaphorase (NADPH-d) can he dividedinto two distinct types, both nonpyramidal. Type I neurons havea large soma (diameter 20–50 µm), a dense NADPH-dhistochemical reaction. and are distributed throughout the cortex,but mainly in the subcortical white matter, and are mostly aspiny.Type II cells have a small soma (< 20 µm) with lightNADPH-d reactivity and are distributed primarily in the supragranularlayers, particularly layers II and upper III. The numericaldensity of type II cells is much greater than that of type I.Type I neurons also stain for GABA and a few intracortical typeI cells contain calbindin. All type II cells found here arecolocalized with both GABA and calbindin. Neither type I nortype II cells are stained for parvalbumin. Together with previous observations that almost all corticalNADPH-d cells in various subprimates are like type I cells,we suggest that type II cells may form a group of NADPH-d-richneurons differentiated in higher mammalian cortex from a subpopulationof calbindin-containing GABAergic interneurons, and these nitricoxide-synthesizing cells may play a role in control of intracorticalneuronal activity characteristic of higher cerebral functionsin advanced mammals.     

Acute and chronic hemodynamic effects of xamoterol in mild to moderate congestive heart failure.

Xamoterol, a new beta 1 partial agonist, has the potential to modulate cardiac response to variations in sympathetic tone in patients with heart failure. Its properties should result in beta-receptor stimulatory effects at low levels of sympathetic tone and beta-receptor protective effects at higher levels of sympathetic tone. The acute effects of intravenous (i.v.) xamoterol on hemodynamics at rest and during exercise were studied in 30 patients with mild to moderate heart failure (13 patients in New York Heart Association class II; 17 in class III) due to ischemic (n = 24) or cardiomyopathic (n = 6) heart disease. Cardiac index, stroke volume and stroke work index at rest were significantly improved after i.v. administration of xamoterol and consistent with net agonist effects. During exercise, heart rate and double product were significantly reduced (net antagonist effects), but with preservation of the expected increases in cardiac index and systolic blood pressure. These hemodynamic findings confirm the ability of xamoterol to modulate cardiac response to variations in sympathetic tone. Tachyphylaxis and arrhythmogenicity limit the chronic use of drugs with full beta-agonist properties as positive inotropes in heart failure. The patients were therefore entered into a 6-month double-blind, placebo-controlled, crossover study of chronic oral xamoterol therapy, 200 mg twice daily, and the hemodynamic responses to i.v. xamoterol were repeated at the end of the trial. No impairment in either resting or exercise effects was observed, indicative of a maintained response and absence of tachyphylaxis after chronic therapy. Furthermore, 24-hour ambulatory electrocardiographic monitoring showed no change in ventricular arrhythmias during oral treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of d-myo-inositol-1,2,6-trisphosphate on neuropeptide Y-induced potentiation of various vasoconstrictor agents in the rat.

The adrenergic cotransmitter neuropeptide Y (NPY) induces vascular smooth muscle contraction by occupying postsynaptic Y1 receptors and by enhancing the vasoconstriction induced by a series of other pressor agents. In particular, NPY modulates the blood pressure response to alpha-1 adrenergic agonists and angiotensin II. The inositol phosphate derivative, d-myo-inositol-1,2,6-trisphosphate (PP56), is a novel NPY antagonist which within a defined dose range selectively blocks the effects of exogenously administered NPY in vivo. In the pithed animal as well as in the freely moving Sprague-Dawley rat, an i.v. bolus administration of PP56 (2 mg/kg) followed by an infusion (20 mg/kg/hr for 30 min) inhibited the approximate 50% increase in mean arterial blood pressure induced by a continuous infusion of NPY (2 micrograms/kg/min for 10 min). Furthermore, PP56 treatment completely inhibited the enhancement induced by NPY (0.1 microgram/min for 50 min or 2 micrograms/kg/min for 10 min) of the pressor responses to preganglionic sympathetic nerve stimulation (in the pithed rat) and to i.v. bolus injections of noradrenaline (20 ng), the indirect sympathomimetic tyramine (40 micrograms) as well as to angiotensin II (10 ng). These results show that PP56, representing a new class of synthetic nonpeptide drugs, is capable of antagonizing the vascular smooth muscle contractile as well as the potentiating effects of NPY in vivo in the pithed as well as the conscious rat.