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In order to study the auditory effects of a metabolic interaction between ethanol and styrene, a first group of rats was gavaged once a day with ethanol (4 g/kg), a second group was exposed to 750 ppm styrene by inhalation, and a third group was exposed to both ethanol and styrene (5 days/week, 4 weeks). Auditory function was tested by recording brainstem (inferior colliculus) auditory evoked potentials, and cochlear hair cell loss was estimated by light microscopy. Cytochrome P450 2E1 and the main urinary styrene metabolites, namely mandelic, phenylglyoxylic and hippuric acids, were measured by high-performance liquid chromatography to check the effects of ethanol on styrene metabolism. In our experimental conditions, ethanol alone did not have any effect on auditory sensitivity, whereas styrene alone caused permanent threshold shifts and outer hair cell damage. Hearing and outer hair cell losses were larger after the exposure to both ethanol and styrene than those induced by styrene alone, indicating a clear potentiation of styrene ototoxicity by ethanol. As expected, metabolic data showed that ethanol alters styrene metabolism and can therefore be considered a modifying factor of styrene toxicokinetics.

Several works have suggested a potential role for nitric oxide in alcohol-seeking behavior and we have recently shown that the specific blockade of the expression of the neuronal nitric oxide synthase (NOS1) decreases rat ethanol intake. Our previous results have also shown that chronic ethanol exposure has differential effect on the brain NOS activity depending on rat brain area. In the present study, we examine the effects of chronic administration of ethanol on the NOS1-mRNA levels measured with the competitive reverse transcriptase-polymerase chain reaction technique. Chronic administration of ethanol differentially regulated NOS1-mRNA levels depending on rat brain area. Chronic ethanol exposure had no effect on the NOS1-mRNA levels in frontal cortex, but decreased the NOS1-mRNA levels in hippocampus (P<0.01, 39% decrease) and induced a strong increase in striatum (P<0.01, 92% increase). These effects of ethanol were not affected by 7-nitro indazole (25 mg/kg, i.p. daily for 1 week) treatment. These data further support that NOS1 is regulated by chronic exposure to ethanol and that these effects are related to modifications of mRNA levels.

To describe the long-term clinical and morphological outcome of symptomatic hepatic cysts treated with percutaneous ethanol sclerotherapy (PES).From December 2003 to September 2011, all patients with hepatic cysts undergoing PES with a follow-up after 12 months were included. Evolution of the volume of the cysts and clinical and biological data were recorded. Features of the cyst were evaluated in each patient: simple, haemorrhagic or developed on underlying polycystic liver disease (PCLD).Fifty-eight cysts (median volume 666 mL) were treated in 57 patients (52 women, mean age 58 years (18-80)). Twenty-two patients (39 %) had simple hepatic cysts, 19 (33 %) had dominant cysts on PCLD and 20 had haemorrhagic cysts (34.5 %), including 4 with PCLD. After a mean 27.3 months of follow-up, the final median cystic volume was 13.5 mL (p < 0.0001), and the median reduction in cyst volume was 94 % (58-100 %). Treatment was satisfactory in 95 % of the patients (54/57) (symptoms disappeared in 45/57 (79 %), decreased in 9/57 (16 %)). There was no clinical or morphological difference between patients with PCLD, haemorrhagic cysts or simple cysts.The clinical and morphological efficacy of a single session of PES is very high, regardless of the presence of intracystic haemorrhage or underlying PCLD.• The clinical efficacy of percutaneous ethanol sclerotherapy is very high. • Haemorrhagic content should not be a contraindication for percutaneous sclerotherapy. • Dominant cysts on polycystic liver disease should be treated with PES. • Imaging follow-up should not be performed shortly after the procedure.

Almost all of the important pathophysiological targets for ethanol in the nervous system appear to be specific membrane proteins involved in signal transduction. In this paper we have examined levels and functionality of the alpha subunit of the Go protein (Goalpha) in cerebral cortex and cerebellum from rats that have chronically ingested ethanol, by using immunoblotting and pertussis toxin-catalyzed ADP-ribosylation experiments. Goalpha protein levels were increased in plasma membranes from the two brain areas, and this increase was shown to specifically affect Go1alpha, one of the two isoforms of the Goalpha subunit. Results obtained here lead us to suggest that increased Go1alpha in plasma membranes would counteract a modified and non-functional protein generated during chronic alcohol treatment.

In order to investigate the biological effects of galactic rays on astronaut cerebral functions after space flight, mice were exposed to different heavy ions (HZE) in whole-body conditions at doses comparable to the galactic flux: 12C, 16O and 20Ne (95 MeV/u, at 42– 76 mGy). Animals were also exposed to 42 mGy of 60Co radiation for comparison with HZE. The neuroimmune response, evaluated by interleukin-1 (IL-1) measurement, showed that this cytokine was produced 3 h after irradiation by 16O or 60Co. In contrast, neither 12C (56.7 mGy) nor 20Ne (76 mGy) induced IL-1 production. However, immunohistochemical staining of 12C-irradiated mouse brain tissue showed 2 months later a marked inflammatory reaction in the hippocampus and a diffuse response in parenchyma. Sleep studies were realized before and after exposure to 42 mGy of 16O and 76 mGy of 20Ne: only the 20Ne radiation displayed a small effect. A slight decrease in paradoxical sleep, corresponding to a reduction in the number of episodes of paradoxical sleep, was manifested between 8 and 22 days after exposure. Exposure to 12C and 16O induced no changes either in cellularity of spleen or thymus, or in caspase 3 activity (as much as four months after irradiation). Taken together, these data indicate that the CNS could be sensitive to heavy ions and that responses to HZE impact depend on the nature of the particle, the dose threshold and the time delay to develop biological processes. Differences in responses to different HZE highlight the complex biological phenomena to which astronauts are submitted during space flight.

Convergent data showed that ethanol exposure during adolescence can alter durably ethanol-related behaviour at adulthood. However, the consequences of juvenile ethanol exposure on the reinforcing effects of other drugs of abuse remain unclear. In the present work, we evaluated in adult male DBA/2J mice the effects of early ethanol exposure on the sensitivity to the incentive effects of cocaine and morphine, and on extracellular signal-regulated kinase (ERK) activation in response to cocaine. Juvenile male mice received intragastric administration of ethanol (2×2.5g/kg/day) or water for 5 days starting on postnatal day 28. When reaching adult age (10 week-old), animals were subjected to an unbiased procedure to assess conditioned place preference (CPP) to cocaine or morphine. In addition, activation of ERK in response to an acute injection of cocaine was investigated using immunoblotting in the striatum and the nucleus accumbens. Mice that have been subjected to early ethanol exposure developed CPP to doses of cocaine (5mg/kg) or morphine (10mg/kg) below the threshold doses to induce CPP in water pre-exposed mice. In addition, early ethanol administration significantly increased striatal ERK phosphorylation normally induced by acute cocaine (10 and 20mg/kg) in adult mice. These results show that, in DBA/2J mice, early exposure to ethanol enhanced the perception of the incentive effects of cocaine and morphine. Ethanol pre-exposure also induced a positive modulation of striatal ERK signalling, in line with the inference that juvenile ethanol intake may contribute to the development of addictive behaviour at adult age.

Nowadays, very few approved anti-relapse treatments for alcoholism exist, and their overall efficacy can be considered moderate. An exciting rationale drug development opportunity for the treatment of chronic alcoholism is the use of acetaldehyde sequestering agents. Although these compounds are able to attenuate or prevent most of the behavioral and neurochemical effects of ethanol, the efficacy of acetaldehyde sequestration, by using agents such as D-penicillamine (DP), in relapse prevention has not been studied yet.The aim of this study was to analyze the effects of DP treatment on the alcohol deprivation effect (ADE) in long-term ethanol-experienced rats as a model of relapse behavior and measure drug plasma and brain levels during treatment.Rats were subcutaneously implanted with mini-osmotic pumps delivering 0, 0.25, or 1 mg/h of DP during 1 week. The efficacy to prevent ADE was determined. DP plasma and brain levels achieved during its subcutaneous administration were measured. In a second experiment, animals received bilateral infusions of 0 or 1.5 μg/h of DP directly into pVTA, and the appearance of ADE was evaluated.One milligram per hour, but not 0.25 mg/h, DP infusion prevented ADE and reduced the total ethanol preference in animals. DP plasma concentrations associated with ADE suppression were around 3-4 μg/ml, and brain DP levels in these conditions were about 2-3 % of those found in plasma. Intra-pVTA DP administration also suppressed ADE.DP is able to prevent alcohol-relapse-like drinking in rats suggesting that this drug may be a useful new tool in the management of relapse in alcohol-dependent patients.

Background In the subacute stroke phase, the monitoring of ambulatory activity and activities of daily life with wearable sensors may have relevant clinical applications. Do current commercially available wearable activity trackers allow us to objectively assess the energy expenditure of these activities? The objective of the present study was to compare the energy expenditure evaluated by indirect calorimetry during the course of a scenario consisting of everyday activities while estimating the energy expenditure using several commercialised wearable sensors in post-stroke patients (less than six months since stroke). Method Twenty-four patients (age 68.2 ± 13.9; post-stroke delay 34 ± 25 days) voluntarily participated in this study. Each patient underwent a scenario of various everyday tasks (transfer, walking, etc.). During the implementation, patients wore 14 wearable sensors (Armband, Actigraph GT3X, Actical, pedometer) to obtain an estimate of the energy expenditure. The actual energy expenditure was concurrently determined by indirect calorimetry. Results Except for the Armband worn on the non-plegic side, the results of our study show a significant difference between the energy expenditure values estimated by the various sensors and the actual energy expenditure when the scenario is considered as a whole. Conclusion The present results suggest that, for a series of everyday tasks, the wearable sensors underestimate the actual energy expenditure values in post-stroke patients in the subacute phase and are therefore not accurate. Several factors are likely to confound the results: types of activity, prediction equations, the position of the sensor and the hemiplegia side.