Effect of Alcohol Sensitivity in Healthy Young Adults on Breath Pharmacokinetics of Acetaldehyde After Mouth Washing with Alcohol.

BACKGROUND: Acetaldehyde is causally related to head and neck cancer. Individuals with aldehyde dehydrogenase 2 deficiency experience alcohol sensitivity and are referred to as "flushers" because of their skin-flushing response to high blood acetaldehyde levels after alcohol consumption. Acetaldehyde is produced in the oral cavity after local alcohol exposure without alcohol ingestion. However, the relationship between the oral acetaldehyde level after local alcohol exposure and alcohol sensitivity is unclear. Herein, sampling the exhaled breath, we evaluated the effect of alcohol sensitivity on the pharmacokinetics of ethanol (EtOH) and acetaldehyde in breath after mouth washing with alcohol. METHODS: Twenty-eight healthy young adults were divided into flusher and nonflusher groups based on an EtOH patch test. The subjects washed their mouths for 30 seconds with 40 ml of 5% v/v alcohol, and their breath samples were collected 12 times over 20 minutes after mouth washing and rinsing with water. EtOH and acetaldehyde concentrations in all breath samples were measured using sensor gas chromatography. RESULTS: Breath EtOH concentrations exponentially decreased in both groups after mouth washing with alcohol. Breath acetaldehyde concentrations showed an immediate increase, followed by an almost exponential decrease in both groups, but concentrations in the flusher group remained higher than those in the nonflusher group throughout the 20-minute measurement period. This was reflected in a peak concentration (Cmax ) of 808 ± 70 parts-per-billion (ppb) versus 1,715 ± 223 ppb, respectively (p = 0.001), and area under the curve values of 3,528 ± 1,399 ppb minutes versus 8,637 ± 1,293 ppb minutes, respectively (p = 0.002). CONCLUSIONS: This study revealed high concentrations of acetaldehyde in breath after local alcohol exposure in the oral cavity among flushers even without alcohol ingestion. This contributes to an increased risk among flushers of mutagenic DNA lesions in the mucosa of the upper digestive tract and cancer.

Acute alcohol response phenotype in heavy social drinkers is robust and reproducible.

BACKGROUND: In 3 previously published works (Brumback et al., 2007, Drug Alcohol Depend 91:10-17; King et al., 2011a, Arch Gen Psychiatry 68:389-399; Roche and King, 2010, Psychopharmacology (Berl) 212:33-44), our group characterized acute alcohol responses in a large group of young, heavy binge drinkers (n = 104) across a variety of subjective, eye-tracking, and psychometric performance measures. METHODS: The primary goal of the current study was to directly replicate prior findings of alcohol response in heavy social drinkers (HD) in a second independent cohort (n = 104) using identical methodology. A secondary goal was to examine the effects of family history (FH) of alcohol use disorders (AUD) on acute alcohol response in both samples. Participants attended 2 randomized laboratory sessions in which they consumed 0.8 g/kg alcohol or a taste-masked placebo. At pre- and post-drink time points, participants completed subjective scales, psychomotor performance and eye-movement tasks, and provided salivary samples for cortisol determination. RESULTS: Results showed that the second cohort of heavy drinkers exhibited a nearly identical pattern of alcohol responses to the original cohort, including sensitivity to alcohol's stimulating and hedonically rewarding effects during the rising breath alcohol content (BrAC) limb, increases in sedation during the declining BrAC limb, a lack of cortisol response, and psychomotor and eye-tracking impairment that was most evident at peak BrAC. The magnitude and temporal pattern of these acute effects of alcohol in the second cohort were similar to the first cohort across all measures, with the exception of 3 eye-movement measures: pro- and antisaccade accuracy and antisaccade velocity. FH of AUD did not affect alcohol response in the first cohort, and this was replicated in the second cohort. CONCLUSIONS: In sum, in 2 independent samples, we have demonstrated that HD display a consistent and reliable sensitivity to alcohol's subjective effects and impairment of eye-tracking and psychomotor performance, which is not affected by FH status. This acute alcohol response phenotype in heavy, frequent binge drinkers appears to be robust and reproducible.

Effects of baclofen on insular gain anticipation in alcohol-dependent patients - a randomized, placebo-controlled, pharmaco-fMRI pilot trial.

RATIONALE: One hallmark of addiction is an altered neuronal reward processing. In healthy individuals (HC), reduced activity in fronto-striatal regions including the insula has been observed when a reward anticipation task was performed repeatedly. This effect could indicate a desensitization of the neural reward system due to repetition. Here, we investigated this hypothesis in a cohort of patients with alcohol use disorder (AUD), who have been treated with baclofen or a placebo. The efficacy of baclofen in AUD patients has been shown to have positive clinical effects, possibly via indirectly affecting structures within the neuronal reward system. OBJECTIVES: Twenty-eight recently detoxified patients (13 receiving baclofen (BAC), 15 receiving placebo (PLA)) were investigated within a longitudinal, double-blind, and randomized pharmaco-fMRI design with an individually adjusted daily dosage of 30-270 mg. METHODS: Brain responses were captured by functional magnetic resonance imaging (fMRI) during reward anticipation while participating in a slot machine paradigm before (t1) and after 2 weeks of individual high-dose medication (t2). RESULTS: Abstinence rates were significantly higher in the BAC compared to the PLA group during the 12-week high-dose medication phase. At t1, all patients showed significant bilateral striatal activation. At t2, the BAC group showed a significant decrease in insular activation compared to the PLA group. CONCLUSIONS: By affecting insular information processing, baclofen might enable a more flexible neuronal adaptation during recurrent reward anticipation, which could resemble a desensitization as previously observed in HC. This result strengthens the modulation of the reward system as a potential mechanism of action of baclofen. TRIAL REGISTRATION: Identifier of the main trial (the BACLAD study) at clinical.gov: NCT0126665.

Effect of menthol on the penetration of tobacco carcinogens and nicotine across porcine oral mucosa ex vivo.

INTRODUCTION: Menthol is a flavored tobacco additive claimed to mask the bitter taste and reduce the harshness of cigarette smoke. (Azzi, C., Zhang, J., Purdon, C. H., Chapman, J. M., Nitcheva, D., Hebert, J. R., et al., 2006, Permeation and reservoir function of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (B[a]P) across porcine esophageal tissue in the presence of ethanol and menthol. Carcinogenesis, 27, 137-145). have shown that menthol increased the flux of tobacco carcinogens (TC) across porcine esophagus. As oral mucosa is exposed to both smoke and smokeless tobacco in tobacco users, the objective of this study was to determine whether menthol influenced the penetration of the TC nitrosonornicotine (NNN) across porcine buccal (BM) and floor of mouth (FM) mucosa. METHODS: Porcine BM and FM were collected at slaughter, mounted in perfusion chambers (n = 7/group), and exposed to tritiated NNN ((3)H-NNN; Amersham, activity 1 muCi/ml) and tritiated nicotine ((3)H-nicotine; Sigma) in 3% nicotine/phosphate-buffered saline (0.01 M, pH 7.4) containing 0.01% unlabeled NNN (National Cancer Institute Chemical Carcinogen Repository) +/- 0.08% menthol for 0.5, 1, 2, or 12 hr. K(p) values (cm/min) were determined and statistically analyzed (analysis of variance, Tukey's, p < .05). RESULTS: FM and BM permeability to both (3)H-NNN and (3)H-nicotine was significantly increased (p < .05) with addition of menthol over that of nicotine alone regardless of exposure times. Even short 30-min menthol exposure significantly increased the flux of both compounds, and this was maintained throughout the experiment. DISCUSSION: Menthol enhances penetration of NNN and nicotine through FM and BM in vitro, even after short exposure. This may reflect loading of a superficial epithelial reservoir (Squier, C. A., Kremer, M. J., Bruskin, A., Rose, A., & Haley, J. D., 1999. Oral mucosal permeability and stability of transforming growth factor beta-3 in vitro. Pharmaceutical Research, 16, 1557-1563.), thus delivering menthol and enhancing flux for several hours. Practical implications are for a potentially increased oral exposure to carcinogens among users of menthol-flavored cigarettes and chewing tobacco.

Analgesic activity of Heliopsis longipes and its effect on the nervous system.

Heliopsis longipes S.F. Blake (Asteraceae: Heliantheae) (chilcuague) is used in Mexican traditional medicine against parasites and to alleviate tooth and muscle pains. Its biocide effect has already been experimentally demonstrated; however, its analgesic action and its action on the nervous system (NS) have not been investigated yet. The objectives of this study were to evaluate the analgesic action of affinin and the H. longipes root ethanol extract, as well as their effects on the NS using an animal model. The ethanol extract was obtained by maceration, and affinin was purified from it through chromatographic techniques. Chemical and thermal analgesia were used to assess their analgesic proprieties. Irwin's test was used to evaluate their stimulating or depressing effects. The ethanol extract and affinin displayed analgesic action similar to ketorolac and stimulating effect comparable to caffeine on the nervous system of adult mice.

[Pharmacological correction of Th1 and Th2 lymphocyte activity and cytokine profile in ethanol intoxicated rats].

It was established in experiments on noninbred rats that their ethanol intoxication (13 days; total dose, 2.6 LD50) significantly reduces the concentration of blood cytokines IFNgamma, IL-2, IL-4, IL-10, increases the concentration of IL-6, suppresses the immune responses, and reduces the interrelation IFNgamma/IL-4 in comparison to the control, which testifies to the greater damage of Th1 cells in comparison to Th2 lymphocytes. The immunomodulator polyoxidonium administered for four days at a daily dose of 700 microg/kg fully restores the cellular and humoral immune responses and the synthesis of cytokines IFNgamma, IL-2, and IL-4 and partly restores the production of IL-10.

Role of the endocannabinoid system in ethanol-induced inhibition of salivary secretion.

AIM: The aim of the present study was to determine whether the endocannabinoid system could be involved in the ethanol-induced inhibition of salivation in adult male Wistar rats. METHODS: Salivary secretion induced by different concentrations of methacholine, a cholinergic agonist, and the endocannabinoid arachidonoyl ethanolamide (anandamide, AEA) production in the submandibular gland (SMG) were determined in rats after ethanol (3 g/kg) administration by gastric gavage. To study the participation of cannabinod receptors in ethanol action, we evaluated methacholine-induced salivary secretion after ethanol administration when CB1 or CB2 receptors were blocked by intra-SMG injections of their selective antagonists AM251 and AM630, respectively. Additionally, we evaluated the in vitro effect of ethanol (0.1 M) on SMG production of cAMP, alone or combined with AM251 or AM630. RESULTS: Acute ethanol administration increased AEA production in SMG and also inhibited the methacholine-induced saliva secretion that was partially restored by intraglandular injection of AM251 or AM630. In addition, ethanol significantly reduced the forskolin-induced increase in cAMP content in SMG in vitro while treatment with AM251 blocked this response. CONCLUSION: We conclude that the inhibitory effect produced by ethanol on submandibular gland salivary secretion is mediated, at least in part, by the endocannabinoid system.

Fabrication and Characterization of Electrospun Nanofibers for the Modified Release of the Chronobiotic Hormone Melatonin.

OBJECTIVE: Aiming at the modified release of melatonin (MLT), electrospun-MLT loaded nanofibers, filled into hard gelatin and DRcapsTM capsules, were used as formulants. METHODS: Cellulose acetate, polyvinylpyrrolidinone and hydroxypropylmethylcellusose (HPMC 2910) were used for the preparation of the fiber matrices through electrospinning. The in vitro modified release profile of MLT from the fabricated matrices in gastrointestinal-like fluids was studied. At pH 1.2, the formulations CA1, CA2, PV1, HP1, HP2 and the composite formulations CAPV1-CAPV5 in hard gelatin capsules exhibited fast MLT release. RESULTS: In general, the same trend was observed at pH 6.8, with the exception of CAPV1 and CAPV2. These two composite formulations delivered 52.08% and 75.25% MLT, respectively at a slower pace (6 h) when encapsulated in DRcapsTM capsules. In all other cases, the release of MLT from DRcapsTM capsules filled with the MLT-loaded nanofibers reached 100% at 6h. CONCLUSION: These findings suggest that the MLT-loaded nanofibrous mats developed in this study exhibit a promising profile for treating sleep dysfunctions.

Influence of the presence of ethanol on in vitro bioavailability of fungicide residues.

The influence of ethanol on the in vitro bioavailability of nine fungicides in wines of varying degrees of alcohol is studied by simulating the digestive process by dialysis in semipermeable membranes. The dose of each fungicide corresponds to its added Maximum Residue Limits in the different matrices (water, ethanol, wines of 7, 11, 13 and 14.5% ethanol). A validated analytical methodology was used which includes extraction, partition according to the modified QuEChERS multiresidue method and liquid chromatography with triple quadrupole tandem mass spectrometry analysis. Interaction between the ethanol content and bioavailability was confirmed and increases were found in the dialyzed percentages with respect to the blank (the standard in water) for ametoctradin, mepanipyrim, cyazofamid, pyraclostrobin and metrafenone, while a decrease was observed for dimethomorph, boscalid and kresoxim-methyl. Fenhexamid showed no significant differences by alcohol content.

Controlled vaporized cannabis, with and without alcohol: subjective effects and oral fluid-blood cannabinoid relationships.

Vaporized cannabis and concurrent cannabis and alcohol intake are commonplace. We evaluated the subjective effects of cannabis, with and without alcohol, relative to blood and oral fluid (OF, advantageous for cannabis exposure screening) cannabinoid concentrations and OF/blood and OF/plasma vaporized-cannabinoid relationships. Healthy adult occasional-to-moderate cannabis smokers received a vaporized placebo or active cannabis (2.9% and 6.7% Δ(9) -tetrahydrocannabinol, THC) with or without oral low-dose alcohol (~0.065g/210L peak breath alcohol concentration [BrAC]) in a within-subjects design. Blood and OF were collected up to 8.3 h post-dose and subjective effects measured at matched time points with visual-analogue scales and 5-point Likert scales. Linear mixed models evaluated subjective effects by THC concentration, BrAC, and interactions. Effects by time point were evaluated by dose-wise analysis of variance (ANOVA). OF versus blood or plasma cannabinoid ratios and correlations were evaluated in paired-positive specimens. Nineteen participants (13 men) completed the study. Blood THC concentration or BrAC significantly associated with subjective effects including 'high', while OF contamination prevented significant OF concentration associations <1.4 h post-dose. Subjective effects persisted through 3.3-4.3 h, with alcohol potentiating the duration of the cannabis effects. Effect-versus-THC concentration and effect-versus-alcohol concentration hystereses were counterclockwise and clockwise, respectively. OF/blood and OF/plasma THC significantly correlated (all Spearman r≥0.71), but variability was high. Vaporized cannabis subjective effects were similar to those previously reported after smoking, with duration extended by concurrent alcohol. Cannabis intake was identified by OF testing, but OF concentration variability limited interpretation. Blood THC concentrations were more consistent across subjects and more accurate at predicting cannabis' subjective effects. Copyright © 2015 John Wiley & Sons, Ltd.

The effect of dimyristoylphosphatidylethanol on the lateral and rotational mobilities of liposome lipid bilayers.

The aim of this study was to provide the basis to further examine the mode of action of ethanol. Fluorescent probes reported to have different membrane mobilities were used to evaluate the effect of dimyristoylphosphatidylethanol (DMPEt) on the lateral and rotational mobilities of liposome lipid bilayers. An experimental procedure, based on the selective quenching of 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1,3-di(1-pyrenyl)propane (Py-3-Py) by trinitrophenyl groups, was used. DMPEt increased the bulk lateral and rotational mobilities, and had a greater fluidizing effect on the outer than the inner monolayer. These effects of DMPEt on liposomes may be responsible for some, but not all, of the general anesthetic actions of ethanol.

Naltrexone effects on diazepam intoxication and pharmacokinetics in humans.

The opiate antagonist naltrexone (NTX) blocks relapse drinking in alcoholics and modifies some of the subjective effects of alcohol intoxication. Benzodiazepines have demonstrated cross-dependence and cross-tolerance to alcohol. Furthermore, benzodiazepine intoxication has effects on mood and psychomotor performance that are similar to alcohol intoxication. The effects of NTX on diazepam intoxication were investigated in non-drug abusing individuals. Eighteen men and eight women were randomly assigned to receive either 50 mg NTX or placebo PO, on two different occasions in a within-subjects, crossover, double-blind protocol. Diazepam was taken by mouth, 90 min after NTX. At -90, 45, 75, 135, 210 min, subjects were tested with repeated assessments of several mood and sensation scales and a computer-generated psychomotor test battery (CTB). Blood samples were also obtained and analyzed for serum diazepam levels. Diazepam induced several sensations and mood effects similar to those induced by alcohol. Negative mood states such as sedation, fatigue, and anxiety were higher for NTX than for placebo. Positive mood states such as friendliness, vigor, liking the effects of diazepam, and feeling high from diazepam were all lower for NTX than for placebo. There were no group differences on the CTB performance. NTX delayed the time to reach peak diazepam levels, so that peak levels occurred at 75 min for placebo compared to 135 min for NTX. A sub-analysis was conducted with 14 subjects who were FHP for alcoholism, but no differences were found on these outcome measures.

Acute effect of simultaneous administration of tryptophan and ethanol on serotonin metabolites in the locus coeruleus in rats.

Using the microdialysis method, we investigated whether the levels of serotonin (5-hydroxytryptamine, 5-HT) and its metabolites, 5-hydroxyindoleacetic acid (5-HIAA) and 5-hydroxytryptophol (5-HTPL), in the locus coeruleus are influenced by tryptophan alone or simultaneous administration of tryptophan and ethanol. Tryptophan (50 mg/kg, i.p.) led to a significant increase in the levels of 5-HIAA, but not 5-HT in the locus coeruleus. However, ethanol (1.25 g/kg) had no effect on the levels of 5-HT and its metabolites. Combined administration of tryptophan and ethanol caused very marked increases in 5-HIAA and 5-HTPL levels in the locus coeruleus. A time lag in the increased 5-HIAA levels between tryptophan alone and tryptophan plus ethanol was observed. Moreover, 5-HIAA levels in the locus coeruleus induced by tryptophan were abolished by microinjection of 5,7-dihydroxytryptamine (150 microg/4 microl) into the dorsal raphe nucleus. Judging from the present results, the serotonergic afferents to the locus coeruleus may originate for about 20-30% from cell bodies located in the dorsal raphe nucleus. Teeth-chattering was significantly detected in the tryptophan plus ethanol-treated rats when compared with the tryptophan-treated rats, but not in the saline-treated controls. These results may suggest that the increased levels of 5-HIAA and 5-HTPL in the locus coeruleus induced by tryptophan are potentiated by ethanol, and that these levels are partly responsible for behavioral activation.

Ethanol-induced injury in rat primary cortical astrocytes involves oxidative stress: effect of idebenone.

Ethanol-induced neurological disorders have recently been characterised. Indeed, evidence has been collected indicating that chronic ethanol consumption leads to direct or indirect changes in the viability of central nervous system cells. Here we investigated the role of free radical overproduction in primary cortical rat astroglial cells undergoing chronic treatment with ethanol (100 microM). In particular, exposure of astroglial cell cultures to ethanol for 12 consecutive days produced an increased release of lactic dehydrogenase, a decrease on glutamine synthase activity being both effects accompanied by decrease in astroglial viability as detected by MTT (Thiazolyl Blue) test. These effects were accompanied by an increased formation of malondialdehyde (a marker of lipid peroxidation) and by abnormal formation of heat shock protein, being both effects antagonised by liposomally entrapped idebenone, a non-peptidyl free radical scavenger. Taken together, these results suggest that ethanol-induced injury on astroglial cells are mediated by abnormal formation of free radical species and this may represent a useful approach in the treatment of ethanol-related brain disorders.

Local anesthetics: special considerations in endodontics.

Local anesthetics are essential for successful endodontic treatment, and their pharmacologic characteristics have special implications for the treatment of painful, chronically-inflamed or necrotic teeth. Their dosages must be limited to prevent toxicity, which may be enhanced by the coadministration of sedative agents or drugs which affect hepatic drug metabolism. Endodontic patients with established central and peripheral sensitization represent special challenges for pain control, since morphogenetic changes resulting from neurogenic inflammation can render pain fibers more resistant to local anesthesia. The use of vasconstrictors with conventional and alternative injection techniques, e.g., intraosseous injections, are necessary to prolong the duration of action of local anesthesia but can place patients with cardiovascular disease at some risk. An appreciation of all of these aspects of local anesthesia in endodontics will better prepare the operator for predictably safe and effective patient care.

Cytotoxicity and apoptotic signalling cascade induced by chelidonine-loaded PLGA nanoparticles in HepG2 cells in vitro and bioavailability of nano-chelidonine in mice in vivo.

Poor oral bioavailability of chelidonine, a bio-active ingredient of Chelidonium majus, showing anti-cancer potentials against cancer cells with multidrug resistance, makes its optimal use rather limited. To address this problem, we encapsulated chelidonine in biodegradable poly(lactide-co-glycolide) (PLGA) polymers and evaluated nano-chelidonine's (NCs) anti-cancer efficacy vis-à-vis free chelidonine (FC) against HepG2 cells and also evaluated its bioavailability in mice. Physicochemical characteristics indicated that stable spherical NC were formed in nanometer size range (123±1.15 nm) with good yield (86.34±1.91%), better encapsulation efficiency (82.6±0.574%), negative surface charge (-19.6±2.48 mV) and ability of prolonged and sustained release of chelidonine. Fourier transform infrared analysis revealed that NC resembled similar peaks as that of FC suggesting effective encapsulation in PLGA. NC exhibited rapid cellular uptake and stronger apoptotic effect (∼46.6% reduced IC50 value) than FC, blocking HepG2 cells at G2/M phase. p53, cyclin-D1, Bax, Bcl-2, cytochrome c, Apaf-1, caspase-9 and caspase-3 expressions also corroborated well to suggest greater anticancer potentials of NC. Our in vivo studies demonstrated NC to be more bio-available than FC and showed a better tissue distribution profile without inducing any toxicity (100 mg/kg bw) in mice. Unlike FC, NC could permeate into brain tissue, indicating thereby NC's better potentials for use in therapeutic oncology.

Bisphenol A attenuates phenylbiguanide-induced cardio-respiratory reflexes in anaesthetized rats.

Bisphenol A (BPA), a toxic chemical released from plastics, produces respiratory arrest and hypotension after a latency. The latency was similar to the reflex apnoea induced by the vagal C fibre stimulation. Therefore, the present study was undertaken to examine the effects of chronic and acute exposure to BPA on cardio-respiratory reflexes elicited by phenylbiguanide (PBG). Acute and chronic experiments were performed on adult female rats. In chronic experiments, the animals were ingested with pellets containing BPA (2 µg/kg body weight) or without BPA (time-matched control) for 30 days. Subsequently, the animals were anaesthetized and prepared for recording blood pressure, ECG and respiratory excursions. PBG was injected through jugular vein to evoke reflexes in these animals. In acute experiments, the PBG reflexes were obtained before and after injecting BPA/ethanol. Also vagal afferent activity was recorded in some rats. In time-matched control rats, PBG produced bradycardia, hypotension and tachypnoea over a period of time. The maximal changes were around 50-65%. In BPA treated group, the PBG-induced heart rate and respiratory frequency changes were attenuated significantly. Acute exposure of animals to BPA (35 mg/kg body weight) for 30 min also attenuated the PBG-induced responses significantly. The attenuation of the PBG reflex responses by BPA in acute experiments was associated with decreased vagal afferent activity. The present results indicate that BPA attenuates the protective cardio-respiratory reflexes due to decreased vagal afferent activity.

Does timing of alcohol administration affect sleep?

STUDY OBJECTIVES: To explore the time of day effects of alcohol on sleep, we examined sleep following alcohol administered at four times of day and three homeostatic loads during a 20-hr forced desynchrony (FD) protocol. PARTICIPANTS: Twenty-six healthy young adults (21-25 yrs) were studied. DESIGN: Participants were dosed at 4 clock times: 0400 (n = 6; 2 females), 1600 (n = 7; 4 females), 1000 (n = 6; 1 female) or 2200 (n = 7; 2 females). Participants slept 2300 to 0800 for at least 12 nights before the in-lab FD study. Double blind placebo and alcohol (vodka tonic targeting 0.05g% concentration) beverages were each administered three times during FD at different homeostatic loads: low (4.25 or 2.24 hrs awake), medium (8.25 or 6.25 hrs awake), high (12.25 or 10.25 hrs awake) in the 0400 and 1600 or 1000 and 2200 groups, respectively. Sleep was staged and subjected to spectral analysis. MEASUREMENTS AND RESULTS: Breath Alcohol Concentration (BrAC) confirmed targeted maximal levels. At bedtime, BrAC was 0 in the low and medium homeostatic load conditions; however, at high homeostatic load, BrAC was still measurable. Spectral characteristics of sleep were unaffected with alcohol at any time of day. Few alcohol related changes were seen for sleep stages; however, with alcohol given at 0400 at a high homeostatic load there was an increase in wake. CONCLUSIONS: These data lend support to the idea that alcohol may be disruptive to sleep; however, our findings are inconsistent with the idea that a low dose of alcohol is a useful sleep aid when attempting to sleep at an adverse circadian phase.

Ingesting alcohol prior to food can alter the activity of the hypothalamic-pituitary-adrenal axis.

There is an increasing evidence that long-term alcohol intake can promote damage to most of the body's major organs. However, regular consumption of a small-moderate amount of alcohol is often recommended as being beneficial to health and of concern is that the effect of ingesting commercially available alcohol products on steroid hormone synthesis under variable nutritional conditions has not been thoroughly investigated. Many individuals consume alcohol alone prior to a meal and the aim of the present study was to assess the effect of consuming a small-moderate amount of commercially available alcohol on the level of salivary cortisol and salivary dehydroepiandrosterone sulfate (DHEAS) before and after a meal. A total of 24 males aged 19-22 years participated in the current investigation. The experimental procedure required participants to fast for 6 h before being asked to ingest either 40 g alcohol in the form of red wine (n=8), low alcohol and high beer (n=8), white wine (n=8) or the equivalent amount of placebo over a 135-min period before consuming food for 45-min. The level of blood alcohol, salivary cortisol and salivary DHEAS was assessed upon arrival and then at regular 45-min intervals during the 180-min experimental period. The results showed that the consumption of alcohol and placebo can significantly lower the level of salivary cortisol. However, the effect of consuming a small-moderate amount of commercially available alcohol on the level of salivary DHEAS was dependent on the nutritional content of the beverage with red wine promoting no change, white wine promoting a significant decrease, and beer having a variable effect on salivary DHEAS concentration when compared to placebo. It was concluded that the effect of commercially available alcohol on the HPA axis is not the same for all alcohol products and both the nutritional status of participants and the nutritional content of the alcoholic beverage being administered should be taken into consideration when investigating the effect of alcohol on the HPA axis.