Peak Blood Alcohol Levels Research Articles

Imaging the brain's immune response to alcohol with [11C]PBR28 TSPO Positron Emission Tomography.

In humans, the negative effects of alcohol are linked to immune dysfunction in both the periphery and the brain. Yet acute effects of alcohol on the neuroimmune system and its relationships with peripheral immune function are not fully understood. To address this gap, immune response to an alcohol challenge was measured with positron emission tomography (PET) using the radiotracer [11C]PBR28, which targets the 18-kDa translocator protein, a marker sensitive to immune challenges. Participants (n = 12; 5 F; 25-45 years) who reported consuming binge levels of alcohol (>3 drinks for females; >4 drinks for males) 1-3 months before scan day were enrolled. Imaging featured a baseline [11C]PBR28 scan followed by an oral laboratory alcohol challenge over 90 min. An hour later, a second [11C]PBR28 scan was acquired. Dynamic PET data were acquired for at least 90 min with arterial blood sampling to measure the metabolite-corrected input function. [11C]PBR28 volume of distributions (VT) was estimated in the brain using multilinear analysis 1. Subjective effects, blood alcohol levels (BAL), and plasma cytokines were measured during the paradigm. Full completion of the alcohol challenge and data acquisition occurred for n = 8 (2 F) participants. Mean peak BAL was 101 ± 15 mg/dL. Alcohol significantly increased brain [11C]PBR28 VT (n = 8; F(1,49) = 34.72, p > 0.0001; Cohen's d'=0.8-1.7) throughout brain by 9-16%. Alcohol significantly altered plasma cytokines TNF-α (F(2,22) = 17.49, p < 0.0001), IL-6 (F(2,22) = 18.00, p > 0.0001), and MCP-1 (F(2,22) = 7.02, p = 0.004). Exploratory analyses identified a negative association between the subjective degree of alcohol intoxication and changes in [11C]PBR28 VT. These findings provide, to our knowledge, the first in vivo human evidence for an acute brain immune response to alcohol.

Licence to swill: James Bond's drinking over six decades.

To describe the patterns of alcohol use in James Bond movies over six decades. Film content analysis. Wide range of international locations in 24 James Bond movies (Eon Productions series, 1962-2015). Drinking episodes for Bond and major female characters; alcohol product placement in films; peak estimated blood alcohol concentrations; features relevant to DSM-5 criteria for alcohol use disorder. Bond has drunk heavily and consistently across six decades (109 drinking events; mean, 4.5 events per movie). His peak blood alcohol level was estimated to have been 0.36 g/dL, sufficient to kill some people. We classified him as having severe alcohol use disorder, as he satisfied six of 11 DSM-5 criteria for this condition. Chronic risks for Bond include frequently drinking prior to fights, driving vehicles (including in chases), high stakes gambling, operating complex machinery or devices, contact with dangerous animals, extreme athletic performance, and sex with enemies, sometimes with guns or knives in the bed. Notable trends during the study period included a decline in using alcohol as a weapon (P = 0.023) and an increase in the number of alcohol products in his environment (for alcohol-related product placement: P < 0.001), but his martini consumption has been steady. Drinking by lead female characters and a random selection of 30 of his sexual partners was fairly stable over time, but also occasionally involved binges. James Bond has a severe chronic alcohol problem. He should consider seeking professional help and find other strategies for managing on-the-job stress.

The Effect of Prenatal Alcohol Exposure on Fetal Growth and Cardiovascular Parameters in a Baboon Model of Pregnancy.

Prenatal alcohol exposure often results in an array of fetal developmental abnormalities termed fetal alcohol spectrum disorders (FASDs). Despite the high prevalence of FASDs, the pathophysiology of fetal damage by alcohol remains poorly understood. One of the major obstacles in studying fetal development in response to alcohol exposure is the inability to standardize the amount, pattern of alcohol consumption, and peak blood alcohol levels in pregnant mothers. In the present study, we used Doppler ultrasonography to assess fetal growth and cardiovascular parameters in response to alcohol exposure in pregnant baboons. Baboons were subjected to gastric alcohol infusion 3 times during the second trimester equivalent to human pregnancy, with maternal blood alcohol levels reaching 80 mg/dL within 30 to 60 minutes following alcohol infusion. The control group received a drink that was isocaloric to the alcohol-containing one. Doppler ultrasonography was used for longitudinal assessment of fetal biometric parameters and fetal cardiovascular indices. Fetal abdominal and head circumferences, but not femur length, were significantly decreased in alcohol-exposed fetuses near term. Peak systolic velocity of anterior and middle cerebral arteries decreased during episodes of alcohol intoxication, but there was no difference in Doppler indices between groups near term. Acute alcohol intoxication affected fetal cerebral blood flow independent of changes in the fetal cardiac output. Unlike fetal growth parameters, changes in vascular indices did not persist over gestation. In summary, alcohol effects on fetal growth and on fetal vascular function have different time courses.

Effects of idazoxan on alcohol pharmacokinetics and intoxication: a preliminary human laboratory study.

Preliminary basic and human studies suggest that the α2 -adrenergic antagonist idazoxan may represent a novel medication for alcohol dependence. The goal of this study was to evaluate the safety and tolerability of the co-administration of idazoxan with alcohol and explore whether pharmacokinetics (PK) and biobehavioral mechanisms of idazoxan may alter alcohol's effects. This was a preliminary double-blind, single-dose, placebo-controlled, crossover, randomized human laboratory study. Ten social drinkers were dosed, in 2 different alcohol challenge studies (ACS), with a single oral dose of idazoxan (40mg) or placebo, followed by a fixed alcohol dose 60minutes later. Participants returned after a 1-week washout, and they were crossed over to the opposite medication condition. There were no significant differences in adverse events between idazoxan and placebo. Moreover, during the ACS paradigm, 40mg idazoxan was well tolerated with no significant autonomic effects compared to placebo; idazoxan reduced the peak blood alcohol level (p<0.01) and time to peak (p<0.05) compared to placebo. A PK/pharmacodynamic model aligned the biobehavioral effects, demonstrating that the co-administration of 40mg idazoxan with alcohol decreased alcohol-related stimulation (p<0.05) and increased alcohol-related sedation (p<0.05). This study supports the safety and tolerability of 40mg idazoxan when co-administered with alcohol. Additionally, this study suggests that idazoxan may alter the biphasic effects of alcohol by decreasing stimulation and increasing sedation. These findings have implications for further investigation of using idazoxan as a probe to develop potential novel medications to treat alcoholic patients.

Ethanol‐induced cardiac fibrosis is mediated by NADPH oxidase (1152.12)

Chronic ethanol (EtOH) abuse leads to cardiomyopathy that is characterized by extensive cardiac fibrosis and dilatation. We hypothesize that EtOH causes cardiac fibrosis by fibroblast activation via NADPH oxidase (NOX)‐induced oxidative stress. Male Sprague‐Dawley rats were intermittently exposed to EtOH vapor for 2 wks (14hr ON/10hr OFF; peak blood alcohol levels of ~200 mg/dL). Time‐matched controls were exposed to room air. Fixed mid‐LV sections stained with picrosirius red were assessed for collagen volume fraction (CVF). To examine the direct effects of EtOH on fibroblasts, isolated adult rat cardiac fibroblasts were treated with EtOH (50mM) for 24 hr, and cell‐conditioned media assayed for hydroxyproline (HPro). Protein expression was determined by Western blot; NOX activity was assessed by NADPH consumption assay; and cellular superoxide production was determined using DHE. Collagen gel contraction assay was used to assess fibroblast activity. In vivo EtOH‐exposure significantly increased LV CVF (1.6% vs 0.9% for control) and NOX‐2 and ‐4 expression (157.0% and 185.6% of control). EtOH significantly increased cardiac fibroblast secretion of collagen (HPro: 1.09±0.09 vs 0.75±0.07 µg/ml for control), and this was prevented by NOX inhibition (DPI; 10µM). EtOH increased fibroblast expression of α‐SMA (150.0% of control) and NOX‐2 (307.2%), but not NOX‐4. EtOH also significantly increased NOX activity (0.39±0.02 vs 0.27±0.00 nmol/mg/min) and superoxide production. EtOH increased gel contraction by fibroblasts (65.4% vs 42.4% control), which was also prevented by NOX inhibition. In conclusion, chronic intermittent EtOH vapor exposure produced cardiac fibrosis, which our data indicate is the result of a NOX‐dependent increase in fibroblast activity and collagen secretion.Grant Funding Source: Supported by an LSUHSC ADACE Pilot Grant (jdg).

Ethanol Promotes Arteriogenesis and Restores Perfusion to Chronically Ischemic Myocardium

Moderate alcohol consumption is known to be cardioprotective compared with either heavy drinking or complete abstinence. We assessed the hypothesis that ethanol supplementation would improve myocardial function in the setting of chronic ischemia. Sixteen male Yorkshire swine underwent placement of an ameroid constrictor into the left circumflex artery to induce chronic myocardial ischemia. Postoperatively, animals were supplemented with either 90 mL of ethanol (EtOH) daily (50%/V, EtOH) or 80 g of sucrose of equal caloric value (SUC), serving as controls. Seven weeks after ameroid placement, arteriolar density (1.74 ± 0.210% versus 3.11 ± 0.368% area of arterioles per low-powered field in sucrose (SUC) versus EtOH; P=0.004), myocardial perfusion (ratio of blood flow to the at-risk myocardium compared with the normal ventricle during demand pacing was 0.585 ± 0.107 versus 1.08 ± 0.138 for SUC versus EtOH; P=0.014), and microvascular reactivity were significantly increased in ethanol-treated animals compared with controls in the at-risk myocardium. Analysis of vascular endothelial growth factor and NOTCH pathway signaling suggested proneovascular and proliferative activity in the ischemic area. The average peak blood alcohol level in the treatment group was 40 ± 4 mg/dL, consistent with levels of moderate drinking in humans. Ethanol supplementation increased arteriolar density and significantly improved myocardial perfusion and endothelium-dependent vasorelaxation in chronically ischemic myocardium. These findings suggest that, at moderate doses, ethanol directly promotes vasculogenesis and improves microvascular function, resulting in significant improvements in myocardial perfusion in the setting of chronic ischemia.

Influence of acute alcohol intoxication on certain immune reactions

Background Long-term alcohol abuse is a potent immunomodulator, and alcohol abusers have increased risk of bacterial infections after surgery. In experiments, acute alcohol intoxication suppresses certain immune reactions and may co-act with trauma to increase risk of post-trauma infectious complications. The aim was to evaluate immune reactions during, an evening of social drinking. Methods We studied 13 healthy, non-smoking volunteers having red wine (1 g of ethanol/kg body weight) with a three course dinner. Delayed type hypersensitivity (DTH) skin test, plasma plasminogen activator inhibitor-1 (PAI-1), plasma myeloperoxidase (MPO) and plasma histamine, representing parts of the immune response with specific relation to the host defence against bacterial antigens, were tested two weeks before the dinner, immediately prior to the dinner, when the blood alcohol level peaked, and one week after the dinner. The volunteers abstained from alcohol in the two weeks leading up to the dinner and one week afterwards. Results The median peak blood alcohol level reached 92 (51-124) mg/dl, equivalent to 20 (11-27) mmol/l. No change in the DTH response was found, p = 0.76. PAI-1 concentration in plasma increased significantly from 3 (1-13) ng/ml just before dinner to 20 (5-75) ng/ml at the time of alcohol peak level, p < 0.01. Similarly, plasma histamine increased from 5.8 (4.7-10) nmol/l to 7.1 (5.6-10) nmol/l, p < 0.01 and plasma MPO decreased from 96 (42-158) to 91 (41-125) ng/ml, p < 0.05. After one week of abstinence, PAI-1, histamine and MPO returned to predinner level. Conclusion The study showed significant changes in various parts of the host’s defence to bacteria following acute alcohol intoxication. Potentially, this may be detrimental for patients, who have been traumatised at injury or surgery during alcohol intoxication, by contributing to enhanced susceptibility to post-trauma bacterial infectious complications. (Less)

The negative effects of alcohol hangover on high-anxiety phenotype rats are influenced by the glutamate receptors of the dorsal midbrain

Alcoholism is a chronic disorder characterized by the appearance of a withdrawal syndrome following the abrupt cessation of alcohol intake that includes symptoms of physical and emotional disturbances, anxiety being the most prevalent symptom. In humans, it was shown that anxiety may increase the probability of relapse. In laboratory animals, however, the use of anxiety to predict alcohol preference has remained difficult. Excitatory amino acids as glutamate have been implicated in alcohol hangover and may be responsible for the seizures and anxiety observed during withdrawal. The dorsal periaqueductal gray (DPAG) is a midbrain region critical for the modulation/expression of anxiety- and fear-related behaviors and the propagation of seizures induced by alcohol withdrawal, the glutamate neurotransmission being one of the most affected. The present study was designed to evaluate whether low- (LA) and high-anxiety rats (HA), tested during the alcohol hangover phase, in which anxiety is the most prevalent symptom, are more sensitive to the reinforcing effects of alcohol when tested in a voluntary alcohol drinking procedure. Additionally, we were interested in investigating the main effects of reducing the excitatory tonus of the dorsal midbrain, after the blockade of the ionotropic glutamate receptors into the DPAG, on the voluntary alcohol intake of HA and LA motivated rats that were made previously experienced with the free operant response of alcohol drinking. For this purpose, we used local infusions of the N-metil D-Aspartato (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-kainate receptors antagonist DL-2-Amino-7-phosphonoheptanoic acid – DL-AP7 (10nmol/0.2μl) and l-glutamic acid diethyl ester – GDEE (160nmol/0.2μl), respectively. Alcohol intoxication was produced by 10 daily bolus intraperitonial (IP) injections of alcohol (2.0g/kg). Peak-blood alcohol levels were determined by gas-chromatography analysis in order to assess blood-alcohol content. Unconditioned and conditioned anxiety-like behavior was assessed by the use of the fear-potentiated startle procedure (FPS). Data collected showed that anxiety and alcohol drinking in HA animals are positively correlated in animals that were made previously familiarized with the anxiolytic effects of alcohol. In addition, anxiety-like behavior induced during alcohol hangover seems to be an effect of changes in glutamatergic neurotransmission into DPAG possibly involving AMPA/kainate and NMDA receptors, among others.

GABRA2 markers moderate the subjective effects of alcohol

Individual differences in subjective responses (SRs) to alcohol are moderated by genetic variants and may be risk factors for the development of alcohol use disorders. Variation in the GABA(A) α2 receptor subunit gene (GABRA2) has been associated with alcohol dependence (AD). Therefore, we examined whether individual differences in SRs, which reflect sensitivity to the effects of alcohol, are associated with variation in GABRA2. Sixty-nine healthy subjects (21-30 years) underwent a laboratory-based within-session cumulative oral alcohol dosing procedure, achieving a mean peak blood alcohol level of 100.4 mg/dl (standard error = 2.5). Subjective assessments were obtained throughout the session, including ascending and descending limbs of the alcohol curve. We genotyped single nucleotide polymorphisms (SNPs) across the chromosome 4 region spanning GABRA2 and analyzed the effect of genotype and haplotypes on subjective responses to alcohol. Population substructure was characterized through the use of ancestry informative markers. Individual SNP analysis demonstrated that carriers of the minor alleles for SNPs rs279858, rs279844, rs279845, rs279826, rs279828 and rs279836 had lower 'Negative' alcohol effects scores than individuals homozygous for the common allele at each SNP (P = 0.0060, P = 0.0035, P = 0.0045, P = 0.0043, P = 0.0037 and P = 0.0061, respectively). Haplotype effects of block 1 showed concordant results with SNPs in this block (P = 0.0492 and P = 0.0150 for haplotypes 1 and 4, respectively). The minor alleles for several of these SNPs have previously been associated with AD. Our findings provide further evidence that variation within GABRA2 is associated with attenuated negative responses to alcohol, a known risk factor for vulnerability to alcohol use disorders.

A behavioral economic supplement to brief motivational interventions for college drinking

Basic behavioral and neurobiological research has demonstrated that deficiencies in naturally occurring substance-free rewards are both a cause and a consequence of substance abuse that are due in part to the systematic discounting of delayed substance-free rewards. Existing brief motivational interventions (BMIs) for alcohol abuse do not target this mechanism of change. The goal of this uncontrolled pilot study was to evaluate a behavioral economic Substance-Free Activity Session (SFAS) to traditional alcohol BMIs. Participants were 13 college freshmen who reported two or more heavy drinking episodes (>5/4 drinks in an occasion for men/women) in the past month. All participants completed a baseline assessment and a BMI that addressed alcohol use. In addition, participants received the SFAS, a 50-min individual session that attempts to increase engagement in constructive alternatives to drinking by enhancing the salience of delayed rewards (academic and career success) and the patterns of behavior (academic and extracurricular engagement) leading to these outcomes. At the 1-month follow-up assessment, participants reported significant reductions in heavy drinking, and moderate to large effect size reductions in weekly drinking and peak blood alcohol levels. The results of this pilot study provide preliminary support for the efficacy of this behavioral economic intervention session as a supplement to traditional alcohol BMIs.

Alcohol and fetal risk: a property of the drink or the drinker?

Alcohol and fetal risk: a property of the drink or the drinker?

S-adenosylmethionine decreases the peak blood alcohol levels 3 h after an acute bolus of ethanol by inducing alcohol metabolizing enzymes in the liver

Introduction An alcohol bolus causes the blood alcohol level (BAL) to peak at 1–2 h post ingestion. The ethanol elimination rate is regulated by alcohol metabolizing enzymes, primarily alcohol dehydrogenase (ADH1), acetaldehyde dehydrogenase (ALDH), and cytochrome P450 (CYP2E1). Recently, S-adenosylmethionine (SAMe) was found to reduce acute BALs 3 h after an alcohol bolus. The question, then, was: what is the mechanism involved in this reduction of BAL by feeding SAMe? To answer this question, we investigated the changes in ethanol metabolizing enzymes and the epigenetic changes that regulate the expression of these enzymes during acute binge drinking and chronic drinking. Methods Rats were fed a bolus of ethanol with or without SAMe, and were sacrificed at 3 h or 12 h after the bolus. Results RT-PCR and Western blot analyses showed that SAMe significantly induced ADH1 levels in the 3 h liver samples. However, SAMe did not affect the changes in ADH1 protein levels 12 h post bolus. Since SAMe is a methyl donor, it was postulated that the ADH1 gene expression up regulation at 3 h was due to a histone modification induced by methylation from methyl transferases. Dimethylated histone 3 lysine 4 (H3K4me2), a modification responsible for gene expression activation, was found to be significantly increased by SAMe at 3 h post bolus. Conclusion These results correlated with the low BAL found at 3 h post bolus, and support the concept that SAMe increased the gene expression to increase the elimination rate of ethanol in binge drinking by increasing H3K4me2.

Connective tissue growth factor production by activated pancreatic stellate cells in mouse alcoholic chronic pancreatitis

Alcoholic chronic pancreatitis (ACP) is characterized by pancreatic necrosis, inflammation, and scarring, the latter of which is due to excessive collagen deposition by activated pancreatic stellate cells (PSC). The aim of this study was to establish a model of ACP in mice, a species that is usually resistant to the toxic effects of alcohol, and to identify the cell type(s) responsible for production of connective tissue growth factor (CTGF), a pro-fibrotic molecule. C57Bl/6 male mice received intraperitoneal ethanol injections for 3 weeks against a background of cerulein-induced acute pancreatitis. Peak blood alcohol levels remained consistently high in ethanol-treated mice as compared with control mice. In mice receiving ethanol plus cerulein, there was increased collagen deposition as compared with other treatment groups as well as increased frequency of α-smooth muscle actin and desmin-positive PSC, which also showed significantly enhanced CTGF protein production. Expression of mRNA for collagen α1(I), α-smooth muscle actin or CTGF were all increased and co-localized exclusively to activated PSC in ACP. Pancreatic expression of mRNA for key profibrotic markers were all increased in ACP. In conclusion, a mouse model of ACP has been developed that mimics key pathophysiological features of the disease in humans and which shows that activated PSC are the principal producers of collagen and CTGF. PSC-derived CTGF is thus a candidate therapeutic target in anti-fibrotic strategies for ACP.

Prenatal choline supplementation mitigates the adverse effects of prenatal alcohol exposure on development in rats

Prenatal alcohol exposure can lead to a range of physical, neurological, and behavioral alterations referred to as fetal alcohol spectrum disorders (FASD). Variability in outcome observed among children with FASD is likely related to various pre- and postnatal factors, including nutritional variables. Choline is an essential nutrient that influences brain and behavioral development. Recent animal research indicates that prenatal choline supplementation leads to long-lasting cognitive enhancement, as well as changes in brain morphology, electrophysiology and neurochemistry. The present study examined whether choline supplementation during ethanol exposure effectively reduces fetal alcohol effects. Pregnant dams were exposed to 6.0 g/kg/day ethanol via intubation from gestational days (GD) 5–20; pair-fed and lab chow controls were included. During treatment, subjects from each group received choline chloride (250 mg/kg/day) or vehicle. Physical development and behavioral development (righting reflex, geotactic reflex, cliff avoidance, reflex suspension and hindlimb coordination) were examined. Subjects prenatally exposed to alcohol exhibited reduced birth weight and brain weight, delays in eye opening and incisor emergence, and alterations in the development of all behaviors. Choline supplementation significantly attenuated ethanol's effects on birth and brain weight, incisor emergence, and most behavioral measures. In fact, behavioral performance of ethanol-exposed subjects treated with choline did not differ from that of controls. Importantly, choline supplementation did not influence peak blood alcohol level or metabolism, indicating that choline's effects were not due to differential alcohol exposure. These data indicate early dietary supplements may reduce the severity of some fetal alcohol effects, findings with important implications for children of women who drink alcohol during pregnancy.

Brain reward deficits accompany withdrawal (hangover) from acute ethanol in rats

Withdrawal from an acute bolus injection of ethanol produces affective or emotional signs that include anxiogenic-like behavior and conditioned place aversion. This study assessed whether brain reward deficits that accompany withdrawal from chronic ethanol dependence are also observed upon withdrawal from acute intoxication. Rats were implanted with stimulating electrodes aimed at the medial forebrain bundle in the lateral hypothalamus and trained on a discrete-trial current-intensity brain stimulation reward threshold paradigm. Ethanol intoxication was produced by bolus intraperitoneal injections of ethanol (1.0, 1.5, or 2.0 g/kg). Brain reward thresholds were monitored periodically following the bolus injection (3, 6, 9, 12, 24, 48, 72, 96 h postethanol). Blood samples taken at various intervals postethanol revealed that peak blood alcohol levels (BAL) at all doses tested were reached within 10 min of injection. Following doses of 1.0, 1.5, and 2.0 g/kg ethanol, BAL had declined to undetectable levels within 3–6 h postinjection. Withdrawal from a single injection of ethanol resulted in a significant but transient increase in brain reward thresholds only with the highest ethanol dose tested (2.0 g/kg). When acute intoxication and withdrawal episodes were repeated two additional times at weekly intervals, the peak magnitude and duration of threshold elevation increased significantly at the 2.0 g/kg dose of ethanol. A significant but transient increase in thresholds was also seen in the group treated with 1.5 g/kg ethanol during the third and final week of testing. Results indicate that withdrawal from a single exposure to an intoxicating dose of ethanol produces significant brain reward deficits in addition to other affective disturbances previously reported, and that repeated weekly intoxication and withdrawal results in a progressive increase in magnitude and duration of the reward deficit.

Disruption of maternal behavior by alcohol intoxication in the lactating rat: a behavioral and metabolic analysis.

Preweanling rats exhibit clear behavioral signs of distress after interacting with an alcohol-intoxicated dam. Interestingly, behavioral reactivity of infants to the experience of alcohol in the nursing context decreases as a function of repeated alcohol administrations to the mother. In this study, maternal activities were examined when dams were exposed to repeated administrations of a subnarcoleptic alcohol dose. Maternal changes in alcohol metabolism were also analyzed as a function of repeated exposures to the drug. During postpartum days 3, 5, 7, 9, 11, and 13, nursing dams received an intragastric administration of either 2.5 g/kg of alcohol or water. Maternal behaviors were evaluated (experiment 1). Blood alcohol levels (BALs) of the dams were determined on postpartum day 16 after all mothers received either an intragastric (experiment 2) or an intraperitoneal (experiment 3) dose of alcohol. The doses used (2.5 g/kg intragastrically and 1.5 g/kg intraperitoneally) were chosen because they promote similar peak BALs in dams naive to alcohol. Maternal behaviors were strongly affected by the state of intoxication. Nevertheless, these disruptions clearly subsided with progression of alcohol-related experiences (experiment 1). Chromatographic analysis of alcohol metabolism indicated the development of tolerance in dams that had prior experience with alcohol (experiment 2). Changes in BALs as a function of prior experience with alcohol seemed related to first-pass alcohol metabolism rather than hepatic oxidative processes of the drug (experiments 2 and 3). When the dam first experiences a moderate state of alcohol intoxication, maternal behaviors are uniformly disrupted. Subsequent exposures to alcohol lead to maternal metabolic tolerance. In conjunction with previous studies, these data indicate that infantile reactivity to alcohol is dependent on how the members of the dam/pup dyad express or perceive ethanol's postabsorptive effects.

Honey-Induced Stimulation of Blood Ethanol Elimination and Its Influence on Serum Triacylglycerol and Blood Pressure in Man

The effect of honey on blood alcohol metabolism and the accompanying changes in serum triacylglycerol and blood pressure were investigated using volunteers. Fifty consenting undergraduates in apparent good health, between the ages of 15 and 30 years (23.6 ± 7.4), were recruited for the study. The subjects were moderate alcohol drinkers (<30 g ethanol/day), matched in body weight and frame size. The participants were given ethanol (0.5 g/kg) and ethanol + honey (0.5 g/kg + 1.25 ml/kg) on two different occasions separated by 1 week. The results show that honey significantly (p < 0.01) increased blood alcohol disappearance and elimination rates by 32.4 and 28.6%, respectively, but reduced the intoxication time (that is, the time taken to attain zero blood alcohol level) and its degree (the peak blood alcohol level) by 30.0 and 4.4%. Ethanol + honey further increased serum triacylglycerol and blood pressure by 20.8 and 1.3/1.4% when compared with the proportion induced by ethanol after about 10 h of ingestion. The occasional use of honey as an anti-intoxicanting agent may be approved. Meanwhile, further studies on how to ameliorate or prevent the associated increase in serum triacylglycerol and blood pressure is required.

Assessment of driver impairment: Evaluation of a two-choice tester using ethanol

Fifteen healthy volunteers aged 18–35 years took part in this three period crossover study evaluating a portable performance tester designed for roadside use. They received by mouth placebo and two doses of ethanol on separate days. Doses were calculated to produce blood alcohol levels of 50 and 80 mg/100 ml. Testing was carried out before the drink and starting at 40 min after the drink. Breathalyser readings showed peak blood alcohol levels of 54.4 mg/100 ml (S.D 11.1) for the smaller dose and 83.0 mg/100 ml (S.D. 8.4) at the larger dose. Significant impairment was seen with the larger dose of ethanol. Response time was increased for the arrow flankers test (attention in the presence of distractors), and errors were increased for paired associates (visuospatial working memory) and for length estimation (judgement). A composite measure showed a clear dose-related pattern of impairment. These results indicate that a short test battery taking about ten minutes to complete can reliably show the effects of ethanol under controlled laboratory conditions. Further work is needed in the field, and with a more varied population to assess the use of such a device to assess impairment due to alcohol and drugs at the roadside.

The role of hypoxia in the pathogenesis of alcoholic liver disease

Research on alcohol-induced liver hypoxia in experimental and clinical alcoholic liver disease (ALD) over a span of 20 years is reviewed. The data has repeatedly supported a role for hypoxia in the pathogenesis of ALD but little attention has been given to this phenomenon in a clinical setting where intervention strategies could be developed. Liver hypoxia, particularly when blood alcohol levels are high, has been documented in vivo in rats fed ethanol continuously at a constant rate for prolonged periods. In this model of ALD, the liver pathology, the liver metabolism and the gene expression differ when the livers are compared at the peak and trough blood alcohol levels as monitored daily by measuring the urinary alcohol level cycle (UAL). Genes regulated by the hypoxia-inducible factor (HIF) are expressed more at the peaks, and the livers contain more inflammation at the peaks. However, alanine aminotransferase levels are higher at the troughs suggesting that hypoxia occurs at the peaks and reperfusion injury occurs at the troughs. These findings may be relevant to binge drinking-induced liver injury where hypoxia at high BAL is followed by normoxia and reoxygination injury when BAL falls toward zero.

The role of hypoxia in the pathogenesis of alcoholic liver disease.

Research on alcohol-induced liver hypoxia in experimental and clinical alcoholic liver disease (ALD) over a span of 20 years is reviewed. The data has repeatedly supported a role for hypoxia in the pathogenesis of ALD but little attention has been given to this phenomenon in a clinical setting where intervention strategies could be developed. Liver hypoxia, particularly when blood alcohol levels are high, has been documented in vivo in rats fed ethanol continuously at a constant rate for prolonged periods. In this model of ALD, the liver pathology, the liver metabolism and the gene expression differ when the livers are compared at the peak and trough blood alcohol levels as monitored daily by measuring the urinary alcohol level cycle (UAL). Genes regulated by the hypoxia-inducible factor (HIF) are expressed more at the peaks, and the livers contain more inflammation at the peaks. However, alanine aminotransferase levels are higher at the troughs suggesting that hypoxia occurs at the peaks and reperfusion injury occurs at the troughs. These findings may be relevant to binge drinking-induced liver injury where hypoxia at high BAL is followed by normoxia and reoxygination injury when BAL falls toward zero.