The effect of ethanol on fat storage in healthy subjects.

BACKGROUND: Ethanol can account for up to 10 percent of the energy intake of persons who consume moderate amounts of ethanol. Its effect on energy metabolism, however, is not known. METHODS: We studied the effect of ethanol on 24-hour substrate-oxidation rates in eight normal men during two 48-hour sessions in an indirect-calorimetry chamber. In each session, the first 24 hours served as the control period. On the second day of one session, an additional 25 percent of the total energy requirement was added as ethanol (mean [+/- SD], 96 +/- 4 g per day); during the other session, 25 percent of the total energy requirement was replaced by ethanol, which was isocalorically substituted for lipids and carbohydrates. RESULTS: Both the addition of ethanol and the isocaloric substitution of ethanol for other foods reduced 24-hour lipid oxidation. The respective mean (+/- SE) decreases were 49.4 +/- 6.7 and 44.1 +/- 9.3 g per day (i.e., reductions of 36 +/- 3 percent and 31 +/- 7 percent from the oxidation rate during the control day; P less than 0.001 and P less than 0.0025). This effect occurred only during the daytime period (8:30 a.m. to 11:30 p.m.), when ethanol was consumed and metabolized. Neither the addition of ethanol to the diet nor the isocaloric substitution of ethanol for other foods significantly altered the oxidation of carbohydrate or protein. Both regimens including ethanol produced an increase in 24-hour energy expenditure (7 +/- 1 percent with the addition of ethanol, P less than 0.001; 4 +/- 1 percent with the substitution of ethanol for other energy sources, P less than 0.025). CONCLUSIONS: Ethanol, either added to the diet or substituted for other foods, increases 24-hour energy expenditure and decreases lipid oxidation. Habitual consumption of ethanol in excess of energy needs probably favors lipid storage and weight gain.

Effect of ethanol on energy expenditure.

The thermogenic response induced by ethanol ingestion in humans has not been extensively studied. This study was designed to determine the thermic effect of ethanol added to a normal diet in healthy nonalcoholic subjects, using indirect calorimetry measurements over a 24-h period in a respiration chamber. The thermic effect of ethanol was also measured when ethanol was ingested in the fasting state, using a ventilated hood system during a 5-h period. Six subjects ingested 95.6 +/- 1.8 (SE) g ethanol in 1 day partitioned over three meals; there was a 5.5 +/- 1.2% increase in 24-h energy expenditure compared with a control day in which all conditions were identical except that no ethanol was consumed. The calculated ethanol-induced thermogenesis (EIT) was 22.5 +/- 4.7% of the ethanol energy ingested. Ingestion of 31.9 +/- 0.6 g ethanol in the fasting state led to a 7.4 +/- 0.6% increase in energy expenditure over baseline values, and the calculated EIT was 17.1 +/- 2.2%. It is concluded that in healthy nonalcoholic adults ethanol elicits a thermogenic response equal to approximately 20% of the ethanol energy. Thus the concept of the apparently inefficient utilization of ethanol energy is supported by these results which show that only approximately 80% of the ethanol energy is used as metabolizable energy for biochemical processes in healthy nonalcoholic moderate ethanol consumers.

Ethanol among randomly controlled drivers

Objectives: Ethanol is well-known to impair driving ability. The major aim of this study was to evaluate the number of drivers driving under the influence of ethanol in a population of randomly controlled drivers. Methods: 1016 drivers were randomly controlled at 27 different locations in Western Switzerland from October 2006 to April 2008. Drivers were controlled for alcohol consumption with a breathalyzer according to the Swiss Road traffic law. If the result was equal or higher than an equivalent of a blood alcohol concentration of 0.8 g/kg, a blood sample was taken; otherwise, a saliva sample was obtained. Blood and saliva were analysed for ethanol by Head-space gas chromatography coupled with a FID detector. Results: Among the controlled drivers, men (69%) predominated over female (31%). The mean age was 41 (range: 16 90). For 968 drivers (95.3%) ethanol was not detected in blood or saliva. These drivers were not under the influence of ethanol. Ethanol was detected in saliva or blood of 48 drivers (4.7%). Among these drivers, blood alcohol concentration (BAC) was above the legal limit of 0.8 g/kg (serious offence) in 14 cases (1.4% of the total population). BAC were in the range of 0.91 to 2.43 g/kg (mean: 1.32 g/kg, median: 1.11 g/kg). Among these 14 cases, men (13 cases, 93%) were over represented. No ethanol was found in the population of truck drivers (17 cases). 986 drivers were car drivers and 46 of them have drunk ethanol (5%). 13 bikers were controlled and 2 of them have drunk ethanol (15%). Conclusion: Driving under the influence of ethanol concerned about 5% of a population of randomly controlled drivers, and 1,4% of the drivers had a blood alcohol concentration higer than 0.8 g/kg (legale limit for a serious offence).

Influence of ethanol dose and pigmentation on the incorporation of ethyl glucuronide into rat hair.

Ethyl glucuronide (EtG) is a minor and specific metabolite of ethanol. It is incorporated into growing hair, allowing a retrospective detection of alcohol consumption. However, the suitability of quantitative EtG measurements in hair to determine the quantity of alcohol consumed has not clearly been demonstrated yet. The purpose of this study was to evaluate the influence of ethanol dose and hair pigmentation on the incorporation of EtG into rat hair. Ethanol and EtG kinetics in blood were investigated after a single administration of ethanol. Eighteen rats were divided into four groups receiving 0 (control group), 1, 2, or 3g ethanol/kg body weight. Ethanol was administered on 4 consecutive days per week for 3 weeks by intragastric route. Twenty-eight days after the initial ethanol administration, newly grown hair was shaved. Pigmented and nonpigmented hair were analyzed separately by gas chromatography coupled to tandem mass spectrometry. Blood samples were collected within 12h after the ethanol administration. EtG and ethanol blood levels were measured by liquid chromatography coupled to tandem mass spectrometry and headspace gas chromatography-flame ionization detector, respectively. No statistically significant difference was observed in EtG concentrations between pigmented and nonpigmented hair (Spearman's rho=0.95). Thus, EtG incorporation into rat hair was not affected by hair pigmentation. Higher doses of ethanol resulted in greater blood ethanol area under the curve of concentration versus time (AUC) and in greater blood EtG AUC. A positive correlation was found between blood ethanol AUC and blood EtG AUC (Spearman's rho=0.84). Increased ethanol administration was associated with an increased EtG concentration in hair. Blood ethanol AUC was correlated with EtG concentration in hair (Pearson's r=0.89). EtG concentration in rat hair appeared to reflect the EtG concentration in blood. Ethanol was metabolized at a median rate of 0.22 g/kg/h, and the median elimination half-life of EtG was 1.21 h. This study supports that the bloodstream is likely to display a major role in the hair EtG incorporation.

Effects of adrenergic blockade on hepatic glucose production during ethanol administration.

Acute ethanol administration stimulates sympathetic nervous system activity. The present study was designed to determine whether this sympathetic activation affects glycogenolysis and total hepatic glucose production (HGP) during ethanol-induced inhibition of gluconeogenesis. Nineteen volunteers participated in four protocols. Two protocols aimed to study--using combined infusion of [6,6-2H2]glucose and [U-13C]glucose, VCO2 and 13CO2 measurements--the effects of ethanol infusion alone (n = 10) or with propranolol (n = 6) or phentolamine infusion (n = 4) on HGP, glucose disposal (Rd), glucose oxidation [13C]Glcox and non-oxidative glucose disposal (NOGD = Rd - [13C]Glcox). The fourth protocol assessed the effects of saline infusion alone on HGP. Using ethanol, HGP decreased by 23%, Rd by 20% and glycaemia by 9% (all P < 0.001); heart rate increased by 10%, whereas blood pressure remained unchanged. The effects were not observed with saline, except a slight (10%) decrease in HGP (P < 0.01 vs. ethanol). Ethanol did not affect [13C]Glcox but decreased NOGD by 73% (P < 0.001). Propranolol or phentolamine did not alter any of the effects of ethanol on glucose metabolism, but decreased mean arterial pressure. Propranolol prevented the ethanol-induced increase in heart rate. In conclusion, ethanol decreased blood glucose by decreasing HGP, presumably by inhibiting gluconeogenesis. Sympathetic activation prevented the decrease in blood pressure produced by ethanol but did not stimulate glycogenolysis.

Adiponectin and heme oxygenase-1 suppress TLR4/MyD88-independent signaling in rat Kupffer cells and in mice after chronic ethanol exposure.

Alcoholic liver disease is mediated via activation of TLR4 signaling; MyD88-dependent and -independent signals are important contributors to injury in mouse models. Adiponectin, an anti-inflammatory adipokine, suppresses TLR4/MyD88-dependent responses via induction of heme oxygenase-1 (HO-1). Here we investigated the interactions between chronic ethanol, adiponectin, and HO-1 in regulation of TLR4/MyD88-independent signaling in macrophages and an in vivo mouse model. After chronic ethanol feeding, LPS-stimulated expression of IFN-β and CXCL10 mRNA was increased in primary cultures of Kupffer cells compared with pair-fed control mice. Treatment of Kupffer cells with globular adiponectin (gAcrp) normalized this response. LPS-stimulated IFN-β/CXCL10 mRNA and CXCL10 protein was also reduced in RAW 264.7 macrophages treated with gAcrp or full-length adiponectin. gAcrp and full-length adiponectin acted via adiponectin receptors 1 and 2, respectively. gAcrp decreased TLR4 expression in both Kupffer cells and RAW 264.7 macrophages. Small interfering RNA knockdown of HO-1 or inhibition of HO-1 activity with zinc protoporphyrin blocked these effects of gAcrp. C57BL/6 mice were exposed to chronic ethanol feeding, with or without treatment with cobalt protoporphyrin, to induce HO-1. After chronic ethanol feeding, mice were sensitized to in vivo challenge with LPS, expressing increased IFN-β/CXCL10 mRNA and CXCL10 protein in liver compared with control mice. Pretreatment with cobalt protoporphyrin 24 h before LPS challenge normalized this effect of ethanol. Adiponectin and induction of HO-1 potently suppressed TLR4-dependent/MyD88-independent cytokine expression in primary Kupffer cells from rats and in mouse liver after chronic ethanol exposure. These data suggest that induction of HO-1 may be a useful therapeutic strategy in alcoholic liver disease.

Fitness to drive and cannabis: Validation of two blood THCCOOH thresholds to distinguish occasional users from heavy smokers.

Many studies based on either an experimental or an epidemiological approach, have shown that the ability to drive is impaired when the driver is under the influence of cannabis. Baseline performances of heavy users remain impaired even after several weeks of abstinence. Symptoms of cannabis abuse and dependence are generally considered incompatible with safe driving. Recently, it has been shown that traffic safety can be increased by reporting the long-term unfit drivers to the driver licensing authorities and referring the cases for further medical assessment. Evaluation of the frequency of cannabis use is a prerequisite for a reliable medical assessment of the fitness to drive. In a previous paper we advocated the use of two thresholds based on 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THCCOOH) concentration in whole blood to help to distinguish occasional cannabis users (≤3μg/L) from heavy regular smokers (≥40μg/L). These criteria were established on the basis of results obtained in a controlled cannabis smoking study with placebo, carried out with two groups of young male volunteers; the first group was characterized by a heavy use (≥10 joints/month) while the second group was made up of occasional users smoking at most 1 joint/week. However, to date, these cutoffs have not been adequately assessed under real conditions. Their validity can now be evaluated and confirmed with 146 traffic offenders' real cases in which the whole blood cannabinoid concentrations and the frequency of cannabis use are known. The two thresholds were not challenged by the presence of ethanol (40% of cases) and of other therapeutic and illegal drugs (24%). Thus, we propose the following procedure that can be very useful in the Swiss context but also in other countries with similar traffic policies: if the whole blood THCCOOH concentration is higher than 40μg/L, traffic offenders must be directed first and foremost toward medical assessment of their fitness to drive. This evaluation is not recommended if the THCCOOH concentration is lower than 3μg/L and if the self-rated frequency of cannabis use is less than 1 time/week. A THCCOOH level between these two thresholds cannot be reliably interpreted. In such a case, further medical assessment and follow-up of the fitness to drive are also suggested, but with lower priority.

Alcohol Brief Intervention in Primary Care: A Systematic Review

BACKGROUND: The purpose of the present review was to evaluate the evidence of the effectiveness of brief interventions aimed at reducing chronic alcohol use and harm related to alcohol consumption, conducted among individuals actively attending primary care but who were not seeking help for alcohol problems. METHODS: Randomised trials reporting at-least one outcome related to alcohol consumption and conducted in outpatients who were actively attending primary care centre or provider were selected using Cochrane Central Register of Controlled Trials, MEDLINE, PsycINFO, ISI Web of Science, ETOH database, and bibliographies of the retrieved references and previous reviews. Selection and data abstraction were performed independently and in duplicate. We assessed validity of the studies and performed a meta-analysis for studies reporting alcohol consumption at 6 or 12 months follow up. RESULTS: We included 24 reports, reporting results of 19 trials and including 5,639 individuals. Seventeen trials reported a measure of alcohol consumption, eight reporting a significant effect of intervention. The meta-analysis showed a mean pooled difference of -41 (95% CI: −54; −28) g of pure ethanol per week in favour of brief intervention group. Evidences for other outcomes (laboratory values, health related quality of life, morbidity and mortality, health care utilisation) were inconclusive. CONCLUSION: Our systematic review indicated that brief intervention might be effective for both men and women in reducing alcohol consumption compared to a controlled intervention, in a primary health care population. The meta-analysis confirmed the reduction in alcohol consumption at 6 and 12 month. Further research should precise the components of effectiveness of brief intervention and the evidence of effects on morbidity, mortality, and quality of life related outcomes.

RecA-mediated annealing of single-stranded DNA and its relation to the mechanism of homologous recombination.

We demonstrate that RecA protein can mediate annealing of complementary DNA strands in vitro by at least two different mechanisms. The first annealing mechanism predominates under conditions where RecA protein causes coaggregation of single-stranded DNA (ssDNA) molecules and where RecA-free ssDNA stretches are present on both reaction partners. Under these conditions annealing can take place between locally concentrated protein-free complementary sequences. Other DNA aggregating agents like histone H1 or ethanol stimulate annealing by the same mechanism. The second mechanism of RecA-mediated annealing of complementary DNA strands is best manifested when preformed saturated RecA-ssDNA complexes interact with protein-free ssDNA. In this case, annealing can occur between the ssDNA strand resident in the complex and the ssDNA strand that interacts with the preformed RecA-ssDNA complex. Here, the action of RecA protein reflects its specific recombination promoting mechanism. This mechanism enables DNA molecules resident in the presynaptic RecA-DNA complexes to be exposed for hydrogen bond formation with DNA molecules contacting the presynaptic RecA-DNA filament.

On problems of calculating energy expenditure and substrate utilization from respiratory exchange data.

Indirect calorimetry based on respiratory exchange measurement has been successfully used from the beginning of the century to obtain an estimate of heat production (energy expenditure) in human subjects and animals. The errors inherent to this classical technique can stem from various sources: 1) model of calculation and assumptions, 2) calorimetric factors used, 3) technical factors and 4) human factors. The physiological and biochemical factors influencing the interpretation of calorimetric data include a change in the size of the bicarbonate and urea pools and the accumulation or loss (via breath, urine or sweat) of intermediary metabolites (gluconeogenesis, ketogenesis). More recently, respiratory gas exchange data have been used to estimate substrate utilization rates in various physiological and metabolic situations (fasting, post-prandial state, etc.). It should be recalled that indirect calorimetry provides an index of overall substrate disappearance rates. This is incorrectly assumed to be equivalent to substrate "oxidation" rates. Unfortunately, there is no adequate golden standard to validate whole body substrate "oxidation" rates, and this contrasts to the "validation" of heat production by indirect calorimetry, through use of direct calorimetry under strict thermal equilibrium conditions. Tracer techniques using stable (or radioactive) isotopes, represent an independent way of assessing substrate utilization rates. When carbohydrate metabolism is measured with both techniques, indirect calorimetry generally provides consistent glucose "oxidation" rates as compared to isotopic tracers, but only when certain metabolic processes (such as gluconeogenesis and lipogenesis) are minimal or / and when the respiratory quotients are not at the extreme of the physiological range. However, it is believed that the tracer techniques underestimate true glucose "oxidation" rates due to the failure to account for glycogenolysis in the tissue storing glucose, since this escapes the systemic circulation. A major advantage of isotopic techniques is that they are able to estimate (given certain assumptions) various metabolic processes (such as gluconeogenesis) in a noninvasive way. Furthermore when, in addition to the 3 macronutrients, a fourth substrate is administered (such as ethanol), isotopic quantification of substrate "oxidation" allows one to eliminate the inherent assumptions made by indirect calorimetry. In conclusion, isotopic tracers techniques and indirect calorimetry should be considered as complementary techniques, in particular since the tracer techniques require the measurement of carbon dioxide production obtained by indirect calorimetry. However, it should be kept in mind that the assessment of substrate oxidation by indirect calorimetry may involve large errors in particular over a short period of time. By indirect calorimetry, energy expenditure (heat production) is calculated with substantially less error than substrate oxidation rates.

Divergent functions of three Candida albicans zinc-cluster transcription factors (CTA4, ASG1 and CTF1) complementing pleiotropic drug resistance in Saccharomyces cerevisiae.

One of the mediators of pleiotropic drug resistance in Saccharomyces cerevisiae is the ABC-transporter gene PDR5. This gene is regulated by at least two transcription factors with Zn(2)-Cys(6) finger DNA-binding motifs, Pdr1p and Pdr3p. In this work, we searched for functional homologues of these transcription factors in Candida albicans. A C. albicans gene library was screened in a S. cerevisiae mutant lacking PDR1 and PDR3 and clones resistant to azole antifungals were isolated. From these clones, three genes responsible for azole resistance were identified. These genes (CTA4, ASG1 and CTF1) encode proteins with Zn(2)-Cys(6)-type zinc finger motifs in their N-terminal domains. The C. albicans genes expressed in S. cerevisiae could activate the transcription of a PDR5-lacZ reporter system and this reporter activity was PDRE-dependent. They could also confer resistance to azoles in a S. cerevisiae strain lacking PDR1, PDR3 and PDR5, suggesting that CTA4-, ASG1- and CTF1-dependent azole resistance can be caused by genes other than PDR5 in S. cerevisiae. Deletion of CTA4, ASG1 and CTF1 in C. albicans had no effect on fluconazole susceptibility and did not alter the expression of the ABC-transporter genes CDR1 and CDR2 or the major facilitator gene MDR1, which encode multidrug transporters known as mediators of azole resistance in C. albicans. However, additional phenotypic screening tests on the C. albicans mutants revealed that the presence of ASG1 was necessary to sustain growth on non-fermentative carbon sources (sodium acetate, acetic acid, ethanol). In conclusion, C. albicans possesses functional homologues of the S. cerevisiae Pdr1p and Pdr3p transcription factors; however, their properties in C. albicans have been rewired to other functions.

Cancer des voies aéro-digestives supérieures (VADS) et types de boissons alcooliques

On ne peut conclure de cette recherche qu'un type de boisson alcoolique soit plus susceptible qu'un autre d'induire un cancer des voies aéro-digestives supérieures (VADS).