Alcohol metabolism contributes to brain histone acetylation.

Emerging evidence suggests that epigenetic regulation is dependent on metabolic state, and implicates specific metabolic factors in neural functions that drive behaviour1. In neurons, acetylation of histones relies on the metabolite acetyl-CoA, which is produced from acetate by chromatin-bound acetyl-CoA synthetase 2 (ACSS2)2. Notably, the breakdown of alcohol in the liver leads to a rapid increase in levels of blood acetate3, and alcohol is therefore a major source of acetate in the body. Histone acetylation in neurons may thus be under the influence of acetate that is derived from alcohol4, with potential effects on alcohol-induced gene expression in the brain, and on behaviour5. Here, using in vivo stable-isotope labelling in mice, we show that the metabolism of alcohol contributes to rapid acetylation of histones in the brain, and that this occurs in part through the direct deposition of acetyl groups that are derived from alcohol onto histones in an ACSS2-dependent manner. A similar direct deposition was observed when mice were injected with heavy-labelled acetate in vivo. In a pregnant mouse, exposure to labelled alcohol resulted in the incorporation of labelled acetyl groups into gestating fetal brains. In isolated primary hippocampal neurons ex vivo, extracellular acetate induced transcriptional programs related to learning and memory, which were sensitive to ACSS2 inhibition. We show that alcohol-related associative learning requires ACSS2 in vivo. These findings suggest that there is a direct link between alcohol metabolism and gene regulation, through the ACSS2-dependent acetylation of histones in the brain.

Effect of sample volume location on Doppler-derived transmitral inflow velocity values in 288 normal subjects 20 to 80 years old: an echocardiographic, two-dimensional color Doppler cooperative study.

The aims of the study were to evaluate in a population of 288 normal subjects 20 to 80 years old (1) the normal values of the indexes of the mitral flow velocity pattern measured either at the tips of the mitral leaflets or at the annulus; (2) whether there was a significant difference between the values obtained at the tips compared with those measured at the mitral annulus; (3) the correlation with aging between the indexes measured in the two different positions; and (4) whether certain physiological variables have different effects on diastolic function measured in the two different positions. The highest values were always measured at the tips of the mitral leaflets (p < 0.05); only atrial filling fraction, E acceleration time, and E deceleration velocity had higher values when measured at the level of the annulus (p < 0.05). The A-wave peak velocity had the same mean value when measured at both the tips and at the annulus. A significant difference in the correlation between parameters measured at the tips of the mitral leaflets with age and at the annulus (with age) was observed for the following parameters: (1) peak E velocity, E integral, total integral and E acceleration showed better correlation with age when measured at the annulus (p < 0.02); (2) peak A velocity and A integral showed better correlation with age when measured at the tips of the mitral leaflets (p < 0.001). Multivariate analysis showed that age was the variable that had the most influence on diastolic function parameters; heart rate had less influence on the diastolic function indexes.

Pulmonary venous flow velocity patterns in 143 normal subjects aged 20 to 80 years old. An echo 2D colour Doppler cooperative study.

In order to find out the normal values and to evaluate the effects of age, heart rate, sex, and haemodynamic and standard echocardiographic parameters on pulmonary venous flow velocity obtained by the transthoracic approach. Doppler pulmonary venous flow parameters were measured in 143 healthy subjects aged from 20 to 80 years. Doppler pulmonary venous flow parameters which had the best correlation with age were: the peak velocity of the systolic wave (r = 0.39) and its integral (r = 0.5), the peak velocity of the diastolic wave (r = -0.6) and its integral (r = -0.44); the systolic (r = 0.68) and diastolic fractions (r = -0.68); the systolic/diastolic peak velocity ratio (r = 0.73) and the systolic/diastolic integral ratio (r = 0.7). The atrial reversal wave did not correlate with age; the atrial reversal wave was more difficult and probably less reliable to measure than the systolic and diastolic waves. The correlations of pulmonary venous flow parameters with mitral flow parameters were also examined. This study showed that, in healthy subjects, despite an increase in the early and atrial waves from the annulus to the tips of the mitral leaflets, there is a similar association between pulmonary venous flow and mitral flow measured at the annulus or at the tips of the mitral leaflets. The intra-observer reproducibility of all the pulmonary venous flow parameters considered were found to be excellent. Moderate inter-observer variability was observed for the systolic, diastolic and atrial reversal wave peak velocities and integrals; however, the systolic/diastolic ratio improved the precision of the measurements. Multivariate analysis showed that age is the principal determinant of the Doppler parameters of pulmonary venous flow: heart rate, sex, body surface area, the size of the left atrium in systole and the left ventricular ejection fraction all influence the Doppler parameters of pulmonary venous flow, even if only slightly.

In vitro antibody secretion by peripheral blood mononuclear cells as an expression of the immune response to Brucella spp. in humans.

We developed an assay to detect antibodies spontaneously secreted in vitro by peripheral blood mononuclear cells (PBMC) against Brucella spp. High levels of anti-Brucella immunoglobulin G (IgG) and/or IgM and/or IgA antibodies were detected in the cell supernatant solution of PBMC cultures for 12 patients suffering from acute or focalized brucellosis and for 5 patients recently vaccinated against brucellosis. This spontaneous in vitro antibody production disappeared 5 to 20 months after onset of clinical signs and 20 to 27 days after vaccination. The transient character of this anti-Brucella antibody production by PBMC is consistent with a temporary in vivo stimulation of the immune system by Brucella antigens. Detection of this secretion could improve the diagnosis of evolutive brucellosis.

[M-mode echocardiography: determination of morphological parameters in the normal newborn infant]. / Ecocardiografia M-mode: determinazione dei parametri morfologici nel neonato normale.

The purpose of this study is to establish normal echocardiographic values of 25 parameters in the newborn infants. The study group is composed of 100 normal, healty neonates (of 72 to 96 hours of age), from whom echocardiograms and measurements were obtained in a standardized manner. Criteria have been established for a complete echocardiographic profile in the full-term newborn. In addition, attempts have been made to correlate the most relevant measurements with body surface area. No significant correlation was found to exist in the small range we have studied (BSA = 0,16 - 0,26 m2).