Plasma Ethanol Concentrations Research Articles

Ethanol Kinetics in the Human Brain Determined by Magnetic Resonance Spectroscopy.

In many parts of the world, ethanol is a widely consumed substance that displays its effect in the brain, the target organ for desired, but also negative impact. In a previous study, the ethanol concentrations were analyzed in different regions of the brain by magnetic resonance spectroscopy (MRS). In this study, the same method is used to demonstrate the kinetics of the ethanol concentration in the human brain after oral ethanol uptake. A drinking study was performed with 10 healthy participants. After the uptake of ethanol in a calculated amount leading to a plasma ethanol concentration of 0.92 g/L (19.95 mM corresponding to a blood ethanol concentration of 0.7 g/kg), brain ethanol concentrations were continuously measured by means of MRS on a 3 Tesla human magnetic resonance imaging (MRI) system. For the data acquisition a single-voxel sLASER sequence was used, with the volume of interest located in the occipital cortex. Intermittently, blood samples were taken and plasma was analyzed for ethanol using headspace gas chromatography with flame ionization detection (HS-GC-FID). The obtained MRS brain ethanol curves showed distinct inter-individual differences; however, a good intra-individual correlation of plasma and brain ethanol concentrations was observed. The results suggest a rapid equilibration between blood and brain. The ethanol concentrations measured in the brain were substantially lower than the measured plasma ethanol results, suggesting an MRS visibility of about 63% for ethanol in brain tissue. The maximum individual ethanol concentrations in the brain (normalized to water content) ranged between 7.1 and 14.1 mM across the cohort, while the highest measured plasma concentrations were in the range between 0.35 g/L (9.41 mM) and 0.95 g/L (20.52 mM).

Combination of alcohol and glucose consumption as a risk to induce reactive hypoglycemia.

Aims/IntroductionAlcohol consumption has been reported to cause hypoglycemia. However, the mechanism involved has not been unequivocally established. This study comprised healthy volunteers. We carried out a prospective trial to compare the effects of glucose and alcohol consumption, alone or in combination, on glucose and lipid metabolism.Materials and MethodsA 75‐g oral glucose tolerance test (OGTT), a combined 75‐g glucose plus 20‐g alcohol tolerance test (OGATT) and a 20‐g alcohol tolerance test (OATT) were carried out in the participants. Plasma glucose, insulin, triglyceride and ethanol concentrations during each test were compared.ResultsWe studied 10 participants. Their plasma glucose concentrations 15 and 30 min after the intake of 75 g of glucose were significantly higher during the OGATT than the OGTT. Hypoglycemia occurred in five participants after the OGATT, which was significantly more frequently than after the OGTT (P = 0.046). Hypoglycemia did not occur after the OATT, and the ethanol concentration was significantly lower after the OGATT than the OATT. The changes in triglyceride concentration from 30 min after the consumption of 75 g of glucose were significantly greater during the OGATT than the OGTT. The plasma insulin concentrations peaked after 60 min during both the OGTT and OGATT, and were significantly higher during the OGATT (P = 0.047). There were no differences between the two interventions in the Matsuda or disposition indexes.ConclusionsHypoglycemia occurred more frequently after the simultaneous consumption of alcohol plus glucose than after the consumption of glucose alone, suggesting that alcohol in the combination of glucose induces reactive hypoglycemia.

Suppressive Effect of Shiitake Extract on Plasma Ethanol Elevation.

Alcohol is usually consumed with meals, but chronic consumption is a leading cause of alcoholic liver diseases. We investigated if shiitake extracts with a high lentinic acid content (Shiitake-H) and without lentinic acid (Shiitake-N) could suppress the elevation in plasma ethanol concentrations by accelerating ethanol metabolism and preventing ethanol absorption from the gut. Shiitake-H and Shiitake-N suppressed the elevation in concentrations of ethanol and acetaldehyde in plasma, and promoted the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in the liver. However, these effects of Shiitake-H were more prominent than those of Shiitake-N. Furthermore, Shitake-H promoted ADH and ALDH activities in the stomach. We also examined the change in plasma ethanol concentration by injecting Shiitake-H or Shiitake-N into the ligated loop of the stomach or jejunum together with an ethanol solution. Shiitake-H suppressed the absorption of ethanol from the stomach and jejunum. In conclusion, Shiitake-H accelerates ethanol metabolism in the stomach and liver and inhibits ethanol absorption in the stomach and jejunum indicating that lentinic acid is a functional component in shiitake.

Effect of Oral Administration of Weissella confusa on Fecal and Plasma Ethanol Concentrations, Lipids and Glucose Metabolism in Wistar Rats Fed High Fructose and Fat Diet.

Background and PurposeIn previous investigations, Weissella confusa was shown to lack the metabolic pathway from fructose to mannitol and to produce ethanol when cultivated in the presence of fructose. Hence, we assessed the effect of oral administration of W. confusa (strain NRRL-B-14171) on blood and fecal ethanol concentrations, glucose and lipid metabolism and traits of the metabolic syndrome in Wistar rats (n=27) fed diets with two different fat and fructose levels and with or without the addition of W. confusa during a total intervention time of 15 weeks (105 days).Materials and MethodsFrom week 1 to 6, rats were given a medium fructose and fat (MFru-MF) diet containing 28% fructose and 10% fat without the addition of W. confusa (control group, n=13) or mixed with 30 g per kg diet of lyophilized W. confusa (10.56 ± 0.20 log CFU/g; W. confusa group, n=14). From week 7 to 15, the percentage of dietary fructose and fat in the control and W. confusa group was increased to 56% and 16%, respectively (high fructose-high fat (HFru-HF) diet).ResultsIn HFru-HF-fed rats, W. confusa was detected in feces, regardless of whether W. confusa was added to the diet or not, but not in rats receiving the MFru-MF diet without added W. confusa or in an additional control group (n=10) fed standard rat food without fructose, increased fat content and W. confusa. This indicates that fecal W. confusa may be derived from orally administered W. confusa as well as – in the case of high fructose and fat intake and obesity of rats – from the intestinal microbiota. As shown by multifactorial ANOVA, blood ethanol, the relative liver weight, serum triglycerides, and serum cholesterol as well as fecal ethanol, ADH, acetate, propionate and butyrate, but not lactate, were significantly higher in the W. confusa – compared to the control group.DiscussionThis is the first in vivo trial demonstrating that heterofermentative lactic acid bacteria lacking the mannitol pathway (like W. confusa) can increase fecal and blood ethanol concentrations in mammals on a high fructose-high fat diet. This may explain why W. confusa resulted in hyperlipidemia and may promote development of NAFLD in the host.

Alcohol Induced Oxidative Stress in neonatal Cardio myocytes

Alcohol Induced Oxidative Stress in neonatal Cardio myocytes

PSIX-7 1H NMR-based plasma metabolomics reveals a potential biomarker of aflatoxin ingestion in dairy cows

Abstract The study applied high-resolution proton nuclear magnetic resonance spectroscopy (1H NMR)-based plasma metabolomics to identify candidate biomarkers of aflatoxin B1 (AFB1) ingestion in dairy cows fed no sequestering agents and evaluate the effect of supplementing clay and/or a Saccharomyces cerevisiae fermentation product (SCFP) on such biomarkers. Eight lactating cows were randomly assigned to 1 of 4 treatments in a balanced 4 × 4 Latin square design with 2 squares. Treatments were control, toxin (T; 1725 µg AFB1/head/day), T with clay (CL; 200 g/head/day), and CL with SCFP (CL+SCFP; 35 g of SCFP/head/day). Cows in T, CL, and CL+SCFP were dosed with AFB1 from d 26 to 30. The sequestering agents were top-dressed from d 1 to 33. On d 30 of each period, 15 mL of blood was taken from the coccygeal vessels and plasma samples were prepared by centrifugation. Plasma sample (200 µL) was subjected to spectral analysis using a 700 MHz Avance III spectrometer. The metabolite data were subjected to statistical analysis using the GLIMMIX procedure of SAS. Biomarker analysis was done using metaboanalyst 4.0. The model included the fixed effects of treatment, period, interaction of treatment and period, and random effects of cow and square. Significance was declared at P ≤ 0.05. Compared to the control, T decreased (P ≤ 0.05) plasma concentrations of alanine, acetic acid, leucine, arginine, and valine. In contrast, T increased plasma ethanol concentration 3.56-fold compared to control. Treatment with CL+SCFP increased concentrations of mannose and 12 amino acids. Based on size of the area under the curve (AUC) of receiver operating characteristic and fold change (FC) analyses, ethanol was the most significantly altered metabolite in T (AUC = 0.88; FC = 3.56); hence, it was chosen as the candidate biomarker of aflatoxin ingestion in dairy cows fed no sequestering agent.

Nonphosphorylatable Src Ser75 Mutation Increases Ethanol Preference and Consumption in Mice.

Src is highly expressed in CNS neurons and contributes not only to developmental proliferation and differentiation but also to high-order brain functions, such as those contributing to alcohol consumption. Src knock-out mice exhibit no CNS abnormalities, presumably due to compensation by other Src family kinases (SFKs), but have a shortened lifespan and osteopetrosis-associated defects, impeding investigations of the role of Src on behavior in adult mice. However, the Unique domain of Src differs from those in other SFKs and is phosphorylated by cyclin-dependent kinase 1 (Cdk1) and Cdk5 at Ser75, which influences its postmitotic function in neurons. Therefore, ethanol consumption in mice harboring nonphosphorylatable (Ser75Ala) or phosphomimetic (Ser75Asp) Src mutants was investigated. Mice harboring the Ser75Ala Src mutant, but not the Ser75Asp mutant, had a higher preference for and consumption of solutions containing 5% and 10% ethanol than wild-type mice. However, plasma ethanol concentrations and sensitivities to the sedative effects of ethanol were not different among the groups. In mice harboring the Ser75Ala Src mutant, the activity of Rho-associated kinase (ROCK) in the striatum was significantly lower and Akt Ser473 phosphorylation was significantly higher than in wild-type mice. These results suggest that Src regulates voluntary ethanol drinking in a manner that depends on Ser75 phosphorylation.

Biomarker of Aflatoxin Ingestion: ¹H NMR-Based Plasma Metabolomics of Dairy Cows Fed Aflatoxin B₁ with or without Sequestering Agents.

The study applied 1H NMR-based plasma metabolomics to identify candidate biomarkers of aflatoxin B1 (AFB1) ingestion in dairy cows fed no sequestering agents and evaluate the effect of supplementing clay and/or a Saccharomyces cerevisiae fermentation product (SCFP) on such biomarkers. Eight lactating cows were randomly assigned to 1 of 4 treatments in a balanced 4 × 4 Latin square design with 2 squares. Treatments were: control, toxin (T; 1725 µg AFB1/head/day), T with clay (CL; 200 g/head/day), and CL with SCFP (CL + SCFP; 35 g of SCFP/head/day). Cows in T, CL, and CL + SCFP were dosed with AFB1 from d 26 to 30. The sequestering agents were top-dressed from d 1 to 33. On d 30 of each period, 15 mL of blood was taken from the coccygeal vessels and plasma samples were prepared by centrifugation. Compared to the control, T decreased plasma concentrations of alanine, acetic acid, leucine, arginine and valine. In contrast, T increased plasma ethanol concentration 3.56-fold compared to control. Treatment with CL tended to reduce sarcosine concentration, whereas treatment with CL + SCFP increased concentrations of mannose and 12 amino acids. Based on size of the area under the curve (AUC) of receiver operating characteristic and fold change (FC) analyses, ethanol was the most significantly altered metabolite in T (AUC = 0.88; FC = 3.56); hence, it was chosen as the candidate biomarker of aflatoxin ingestion in dairy cows fed no sequestering agent.

S-Allyl-L-cysteine sulfoxide, a garlic odor precursor, suppresses elevation in blood ethanol concentration by accelerating ethanol metabolism and preventing ethanol absorption from gut.

Alcoholic beverages are enjoyed together with meals worldwide, but their excessive intake is associated with an increased risk of various diseases. We investigated whether S-allyl-L-cysteine sulfoxide (ACSO), a sulfuric odor precursor of garlic, suppresses elevation in plasma ethanol concentration by accelerating ethanol metabolism and preventing ethanol absorption from the gut in rats. ACSO and garlic extract with a high ACSO content (Garlic-H) suppressed elevation in concentrations of ethanol and acetaldehyde in plasma and promoted the activities of alcohol dehydrogenase and aldehyde dehydrogenase. However, ACSO and Garlic-H did not affect plasma acetate so much. Furthermore, we examined the change in plasma ethanol concentration by injecting ACSO or Garlic-H into the ligated stomach or jejunum together with ethanol solution. ACSO and Garlic-H suppressed the absorption of ethanol from the stomach and jejunum, but suppression in the jejunum was less than in the stomach. In conclusion, ACSO inhibits ethanol absorption and accelerates ethanol metabolism.

Effect of Beverage Containing Fermented Akebia quinata Extracts on Alcoholic Hangover.

The present study was conducted to investigate the effects of beverages containing fermented Akebia quinata extracts on alcoholic hangover. For this study, 25 healthy young men were recruited. All participants consumed 100 mL of water (placebo), commercial hangover beverage A or B, fermented A. quinata leaf (AQL) or fruit (AQF) extract before alcohol consumption. After 1 h, all participants consumed a bottle of Soju, Korean distilled liquor (360 mL), containing 20% alcohol. Blood was collected at 0 h, 1 h, 3 h, and 5 h after alcohol consumption. The plasma alanine transaminase (ALT) activity was highest in the placebo group. Compared with the control group, the AQL and AQF groups showed decreased ALT activity at 5 h after alcohol consumption. Plasma ethanol concentration was increased after alcohol intake and peaked at 3 h after alcohol consumption. Compared with the control group, the A group showed a higher plasma ethanol concentration at 1 h (P<0.05). At 3 h after alcohol consumption, the AQF group showed the lowest mean plasma ethanol concentration compared to the other groups; however, there were no statistical differences. After 5 h of alcohol consumption, the AQL and AQF groups showed lower plasma ethanol concentrations compared with the B group. The sensory evaluation score for the fermented A. quinata fruit extract was lower than for the commercial hangover beverages. In conclusion, the present intervention study results suggest that fermented A. quinata extracts alleviate alcoholic hangover and reduce plasma ethanol concentrations.

Ethanol induces hydroxytyrosol formation in humans

Previous studies in animals have shown an increase of hydroxytyrosol (OHTyr), a potent phenolic antioxidant and a minor metabolite of dopamine (also called 3,4-dihydroxyphenylethanol or DOPET), after ethanol intake. The interaction between ethanol and dopamine metabolism is the probable mechanism involved. The aim of the study was to establish the contribution of the dose of ethanol on OHTyr formation. 24 healthy male volunteers were included. Subjects were distributed in three different cohorts and each volunteer received two doses of ethanol or placebo. Doses of ethanol administered were 6, 12, 18, 24, 30 and 42g. Study design was double-blind, randomized, crossover and controlled. Hydroxytyrosol, tyrosol (Tyr), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) urinary excretion, ethanol plasma concentrations and drunkenness were evaluated along a 6-h period. Urinary excretion of OHTyr and Tyr increased with ethanol administered dose. A reduction in the ratio DOPAC/OHTyr from placebo to the highest dose was observed, compatible with a shift in the dopamine metabolism to preferently produce OHTyr instead of DOPAC. Also a dose-dependent increase in plasma ethanol concentrations and subjective effects was observed. This study demonstrates an endogenous production of OHTyr and Tyr in relation to ethanol administered dose in humans. Biological effects of both phenols from this source should be investigated in future studies.

Maternal alcohol consumption in pregnancy enhances arterial stiffness and alters vasodilator function that varies between vascular beds in fetal sheep.

While the impact of alcohol consumption by pregnant women on fetal neurodevelopment has received much attention, the effects on the cardiovascular system are not well understood. We hypothesised that repeated exposure to alcohol (ethanol) in utero would alter fetal arterial reactivity and wall stiffness, key mechanisms leading to cardiovascular disease in adulthood. Ethanol (0.75 g (kg body weight)(-1)) was infused intravenously into ewes over 1 h daily for 39 days in late pregnancy (days 95-133 of pregnancy, term ∼147 days). Maternal and fetal plasma ethanol concentrations at the end of the hour were ∼115 mg dl(-1), and then declined to apparent zero over 8 h. At necropsy (day 134), fetal body weight and fetal brain-body weight ratio were not affected by alcohol infusion. Small arteries (250-300 μm outside diameter) from coronary, renal, mesenteric, femoral (psoas) and cerebral beds were isolated. Endothelium-dependent vasodilatation sensitivity was reduced 10-fold in coronary resistance arteries, associated with a reduction in endothelial nitric oxide synthase mRNA (P = 0.008). Conversely, vasodilatation sensitivity was enhanced 10-fold in mesenteric and renal resistance arteries. Arterial stiffness was markedly increased (P = 0.0001) in all five vascular beds associated with an increase in elastic modulus and, in cerebral vessels, with an increase in collagen Iα mRNA. Thus, we show for the first time that fetal arteries undergo marked and regionally variable adaptations as a consequence of repeated alcohol exposure. These alcohol-induced vascular effects occurred in the apparent absence of fetal physical abnormalities or fetal growth restriction.

Pharmacokinetic/Pharmacodynamic (PK/PD) Relationship-based Approach to Understand the Variability of Central Neurological Effects of Ethanol

Pharmacokinetic/pharmacodynamic (PK/PD) relationships describe the quantitative relationships between the drug-induced effects and the concurrent corresponding drug concentrations in an individual. Since a long time, rough qualitative relationships have been described between neurological presentation and plasma ethanol concentration in acute ethanol ingestion. However, to date, precise quantitative PK/PD relationships have not been extensively studied. We studied PK/PD relationships in ethanol poisonings. Plasma concentrations were measured using an enzymatic assay. Coma depth was assessed using the Glasgow Coma Scale (GCS). Non-linear regression was used for modeling PK/PD relationships. The PK/PD relationships were well fitted with the sigmoidal Emax model. A maximal toxic effect (GCS of 3) was associated with a wide range of plasma ethanol concentrations, suggesting the saturation of drug targets at high doses. During the course of poisoning, the relationships between the depth of coma and the corresponding plasma concentrations were of sigmoidal shape. The elevated values of the Hill coefficient showed that a small decrease in plasma concentrations near the EC50 was associated with a dramatic improvement in the level of consciousness. In chronic alcoholic patients, EC50 was higher than in non-tolerant. Analyzing blood concentrations with respect of the delay elapsed since the ingestion may help predicting the time of awakening and thus the evaluation of outcome. In conclusion, PK/PD relationships are helpful in suggesting mechanisms of inter-individual variability of central neurological response to ethanol.

Alcohol metabolism are improved by yeast extract mixtures than Hovenia Dulcis mixtures in healthy men: a double‐blind, randomized crossover, placebo‐controlled trial (LB441)

Alcohol hangover is an unpleasant aftermath of heavy alcohol drinking. Hangover onset starts after the oral administration of alcohol since ethanol, a key component of the alcoholic drinks, metabolized to acetaldehyde. In this study, we investigated whether the supplement formula might improve the alcohol metabolism in healthy adult men. In a double‐blinded, randomized, crossover study, subjects were received yeast extract mixtures (YEM, n=21), Hovenia Dulcis mixtures (HDM, n=21), placebo (PLC, n=21), and control (CON, n=21) in separate 4 week supplementation periods at a single oral dose followed by one week washout periods. At each visit (0, 1, 2, 3, 4 weeks), the subjects drank 450 mL 23 % alcohol simultaneously with mixtures and blood was drawn periodically (0, 0.25, 0.5, 1, 2, 4, 6, 15 hr). Fifteen subjects completed the protocol and included in the analysis. The plasma ethanol concentrations were tended to lower in the YEM (10 %) and the HDM (5 %) groups. The area under the curves (AUCs) and Cmax for plasma ethanol were significantly decreased only in the YEM group, when compared with the CON group. The AUCs and Cmax for plasma acetaldehyde concentration were significantly decreased in the YEM (45 % and 54 %) and the HDM (35 % and 53 %) groups respectively, when compared with PLC (P&lt;0.01). These findings demonstrated that alcohol metabolism and hangover syndromes might improve by YEM than HDM.

Endogenous Methanol Regulates Mammalian Gene Activity

We recently showed that methanol emitted by wounded plants might function as a signaling molecule for plant-to-plant and plant-to-animal communications. In mammals, methanol is considered a poison because the enzyme alcohol dehydrogenase (ADH) converts methanol into toxic formaldehyde. However, the detection of methanol in the blood and exhaled air of healthy volunteers suggests that methanol may be a chemical with specific functions rather than a metabolic waste product. Using a genome-wide analysis of the mouse brain, we demonstrated that an increase in blood methanol concentration led to a change in the accumulation of mRNAs from genes primarily involved in detoxification processes and regulation of the alcohol/aldehyde dehydrogenases gene cluster. To test the role of ADH in the maintenance of low methanol concentration in the plasma, we used the specific ADH inhibitor 4-methylpyrazole (4-MP) and showed that intraperitoneal administration of 4-MP resulted in a significant increase in the plasma methanol, ethanol and formaldehyde concentrations. Removal of the intestine significantly decreased the rate of methanol addition to the plasma and suggested that the gut flora may be involved in the endogenous production of methanol. ADH in the liver was identified as the main enzyme for metabolizing methanol because an increase in the methanol and ethanol contents in the liver homogenate was observed after 4-MP administration into the portal vein. Liver mRNA quantification showed changes in the accumulation of mRNAs from genes involved in cell signalling and detoxification processes. We hypothesized that endogenous methanol acts as a regulator of homeostasis by controlling the mRNA synthesis.

The effects of low-moderate dose prenatal ethanol exposure on the fetal and postnatal rat lung.

Little is known about whether exposure of the fetus to alcohol alters pulmonary development or function. This study aimed to determine whether low-moderate ethanol (EtOH) exposure throughout gestation alters structural and non-respiratory functional aspects of the fetal and postnatal lung. Sprague-Dawley rats were fed an ad libitum liquid diet ±6% v/v EtOH daily throughout pregnancy, achieving a plasma ethanol (EtOH) concentration of 0.03%. Gene and protein expression was determined in pulmonary tissue collected from fetuses at embryonic day (E) 20 and adult offspring. The percentage of airspace and alveolar size was measured in pulmonary tissue collected at postnatal day (PN) 1. At E20, EtOH-exposed fetuses had decreased aquaporin 5 mRNA levels and a non-significant trend for decreased epithelial sodium channel type α; expression of other pulmonary fluid homeostatic and development genes and surfactant protein genes were not different between groups. At PN1, there was no difference between EtOH-exposed and control offspring in the distal airspace percentage or diameter. At 8 months, collagen type III α1 gene expression was upregulated in EtOH-exposed male offspring; this was associated with increased collagen deposition at 10 months. At 19 months, male EtOH-exposed offspring had a 25% reduction in the protein levels of surfactant protein B. The alterations observed in male EtOH-exposed offspring suggest chronic low-moderate prenatal EtOH-exposure during development may result in increased pulmonary fibrosis. Such an alteration would decrease the respiratory capacity of the lung.

Meconium Fatty Acid Ethyl Esters as Biomarkers of Late Gestational Ethanol Exposure and Indicator of Ethanol-Induced Multi-Organ Injury in Fetal Sheep

BackgroundMeconium fatty acid ethyl esters (FAEE) constitute a biomarker of heavy fetal ethanol exposure. Our objective was to measure meconium FAEE in fetal sheep following daily, relatively moderate-dose ethanol exposure in late gestation, and to evaluate their utility in identifying fetal organ-system injury.MethodsPregnant ewes received ethanol (0.75 g/kg; n = 14) or saline (n = 8) via 1-h IV infusion daily during the third trimester equivalent, while additional pregnant sheep served as untreated controls (n = 6). The daily ethanol regimen produced similar maximal maternal and fetal plasma ethanol concentrations of 0.11–0.12 g/dL. Ewes and fetuses were euthanized shortly before term, and meconium was collected and analyzed for FAEE (ethyl palmitate, stearate, linoleate, and oleate).ResultsMeconium total FAEE concentration was significantly higher in ethanol-exposed fetuses compared with controls, and a positive cut-off of 0.0285 nmol total FAEE/g meconium had 93.3% sensitivity and specificity for detecting fetal ethanol exposure. When the studied animals (ethanol-exposed and controls) were classified according to meconium FAEE concentration, FAEE-positive and FAEE-negative groups frequently differed with respect to previously examined pathological endpoints, including nephron endowment, lung collagen deposition, cardiomyocyte maturation, and tropoelastin gene expression in cerebral vessels. Furthermore, in all studied animals as a group (ethanol-exposed and controls combined), meconium FAEE concentration was correlated with many of these pathological endpoints in fetal organs.ConclusionsWe conclude that, in fetal sheep, meconium FAEE could serve as a biomarker of daily ethanol exposure in late gestation and could identify fetuses with subtle ethanol-induced toxic effects in various organs. This study illustrates the potential for using meconium FAEE to identify neonates at risk for dysfunction of major organs following in-utero ethanol exposure that does not result in overt physical signs of ethanol teratogenicity.

Exacerbation of myocardial dysfunction and autonomic imbalance contributes to the estrogen-dependent chronic hypotensive effect of ethanol in female rats

Our previous studies showed that the hypotensive effect of chronic ethanol in female rats is reduced by ovariectomy (OVX) rats and was restored after estrogen replacement (OVXE2). Further, in randomly cycling rats, chronic ethanol increased cardiac parasympathetic dominance and subsequently reduced myocardial contractility and blood pressure (BP). In this study, we tested the hypothesis that alterations in myocardial contractility and sympathovagal control account for the E2 exacerbation of the hemodynamic effects of ethanol. BP, myocardial contractility (+dP/dtmax), and spectral cardiovascular autonomic profiles were evaluated in radiotelemetered OVX, and OVXE2 rats receiving liquid diet with or without ethanol (5%, w/v) for 13weeks. In OVX rats, ethanol caused modest hypotension along with significant increases in +dP/dtmax during weeks 2–5. The high-frequency (IBIHF, 0.75–3Hz) and low-frequency (IBILF, 0.25–0.75Hz) bands of interbeat intervals were briefly increased and decreased, respectively, by ethanol. Compared with its effects in OVX rats, chronic treatment of OVXE2 rats with ethanol elicited significantly greater and more sustained reductions in systolic (SBP) and diastolic (DBP) blood pressures and +dP/dtmax. Altered sympathovagal balance and parasympathetic overactivity were more evident in ethanol-treated OVXE2 rats as suggested by the sustained: (i) increases in high-frequency bands of interbeat intervals (IBIHF, 0.75–3Hz), and (ii) decreases in low-frequency IBI bands (IBILF, 0.25–0.75Hz), IBILF/HF ratio and +dP/dtmax. The plasma ethanol concentration was not affected by changes in the hormonal milieu. These findings suggest that estrogen exacerbates the ethanol-evoked reductions in myocardial contractility and BP and the associated parasympathetic overactivity in female rats.

The frequency of daily ethanol consumption influences the effect of ethanol on insulin sensitivity in rats fed a high-fat diet

The different effects of ethanol on insulin sensitivity may be due to complex reasons. Here, we focus on the various daily ethanol consumption frequencies in rats fed a high-fat (HF) diet and explore the possible mechanism mediated by adiponectin and AMP-activated protein kinase (AMPK). A total of thirty-six male Wistar rats were fed a HF diet and were randomly divided into three groups: those that received tap water (C); those that received ethanol via a gastric tube twice per d (E1); those that received free access to ethanol for drinking (E2). The total daily ethanol dosage in groups E1 and E2 were the same (5 g/kg per d). At the end of 18 weeks, insulin sensitivity was evaluated. Adiponectin AMPK and GLUT4 levels were determined. We found that the different administration frequencies led to markedly different plasma ethanol concentrations and there were intimate relationships between plasma ethanol concentration and insulin sensitivity. Insulin resistance was markedly improved in group E1, whereas only a slight improvement was observed in group E2. Accordingly, adiponectin, phosphorylated AMPK and GLUT4 levels were significantly increased in group E1. Based on these findings, we propose that ethanol concentration might be the major influencing factor mediating the effect of ethanol on insulin sensitivity. At a total daily dosage of 5 g/kg per d, twice daily administration of ethanol was more beneficial than continuous drinking. The protective effect of ethanol might be mediated by increased adiponectin levels, which subsequently improve the activation of AMPKα and GLUT4 expression in adipose tissue.

Biomarkers of recent drinking, retrograde extrapolation of blood-alcohol concentration and plasma-to-blood distribution ratio in a case of driving under the influence of alcohol

This case report describes the police investigation of a road-traffic accident involving a collision at night (01.00 am) between a car and a truck in which a passenger in the car was killed. The driver of the truck was found responsible for the crash although a roadside breath-alcohol test was negative (<0.1 mg/L breath or 20 mg/100 mL blood). Because of injuries sustained in the crash, the female driver of the car was not breath-tested at the time but was transported to a local hospital for emergency treatment. After swabbing the skin with isopropanol an indwelling catheter was inserted at 01.40 am. A blood sample was taken at 02.10 am and the plasma portion contained 8 mmol/L ethanol according to analysis at the hospital clinical laboratory using a gas chromatographic method. Another blood sample was taken at 05.45 am for analysis of ethanol at a forensic toxicology laboratory, although the result was negative (<10 mg/100 mL). The police authorities wanted an explanation for the discrepancy between the clinical and forensic laboratory results and inquired whether the driver of the car was above the legal alcohol limit (>20 mg/100 mL) at the time of the crash. The scientific basis for converting a plasma-ethanol concentration into a blood-ethanol concentration and back extrapolation of the driver’s blood-alcohol concentration (BAC) is explained. The risk of contaminating a blood sample by swabbing the skin with isopropanol is discussed along with the use of alcohol biomarkers (ethyl glucuronide and ethyl sulphate) as evidence of recent drinking.