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Alcohol Levels (alcohol + level)
Kinds of Alcohol Levels Selected AbstractsOperant Behavior and Alcohol Levels in Blood and Brain of Alcohol-Dependent RatsALCOHOLISM, Issue 12 2009Nicholas W. Gilpin Background:, The purpose of the present investigation was to more clearly define blood-alcohol parameters associated with alcohol dependence produced by alcohol vapor inhalation and alcohol-containing liquid diet. Methods:, Alcohol levels in blood and brain were compared during and after 4 hours of acute alcohol vapor exposure; also, brain-alcohol levels were assessed in alcohol-exposed (14-day alcohol vapor) and alcohol-naïve rats during and after 4 hours of acute alcohol vapor exposure. A separate group of rats were implanted with i.v. catheters, made dependent on alcohol via vapor inhalation, and tested for operant alcohol responding; blood-alcohol levels (BALs) were measured throughout operant alcohol drinking sessions during alcohol withdrawal. A final group of rats consumed an alcohol-liquid diet until they were dependent, and those rats were then tested for operant behavior at various withdrawal time points; BALs were measured at different withdrawal time points and after operant sessions. Results:, Blood- and brain-alcohol levels responded similarly to vapor, but brain-alcohol levels peaked at a higher point and more slowly returned to zero in alcohol-naïve rats relative to alcohol-exposed rats. Alcohol vapor exposure also produced an upward shift in subsequent operant alcohol responding and resultant BALs. Rats consumed large quantities of alcohol-liquid diet, most of it during the dark cycle, sufficient to produce high blood-alcohol levels and elevated operant alcohol responding when tested during withdrawal from liquid diet. Conclusions:, These results emphasize that the key determinants of excessive alcohol drinking behavior are the BAL range and pattern of chronic high-dose alcohol exposure. [source] Hands-free mobile phone conversation impairs the peripheral visual system to an extent comparable to an alcohol level of 4,5,g 100,mlHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 1 2005Peter Langer No abstract is available for this article. [source] Idiographically Determined Versus Standard Absorption Periods in Alcohol Administration StudiesALCOHOLISM, Issue 5 2010Rebecca L. Schacht Background:, Effects of alcohol vary depending on blood alcohol level and limb. Some researchers use standard absorption periods (SAPs) to determine when postdrinking experimental protocols should begin. Others use an idiographically determined absorption period (IDAP) based on criterion breath alcohol concentration (BrAC). We investigated and compared the characteristics of each method. Methods:, Sixty-eight social drinkers (47% women) consumed a bolus dose of alcohol intended to raise BrAC to 0.08%. BrACs were recorded every 3 minutes until beginning to descend. Minutes to reach criterion BrAC (0.06%) and between-subjects postdrinking BrAC variability were analyzed. Results:, Mean time to reach 0.06% BrAC was 22.9 ± 14.6 minutes. Standard deviations in BrAC were 4 times greater using SAPs compared to IDAPs. Ten percent of participants' BrAC readings were on the descending limb 30 minutes postdrinking, and 25% were descending at 45 minutes postdrinking. Conclusions:, IDAPs result in less BrAC variability and may reduce experimental noise relative to SAPs. Experimental control in future alcohol administration studies may be enhanced by the use of IDAPs instead of SAPs. [source] Alcohol-Induced Electrical Remodeling: Effects of Sustained Short-Term Ethanol Infusion on Ion Currents in Rabbit AtriumALCOHOLISM, Issue 10 2009Roman Laszlo Background:, In some patients, above-average alcohol consumption before occurrence of atrial fibrillation (AF) in terms of a "holiday heart syndrome" (HHS) can be determined. There is evidence that long before development of apparent alcohol-induced cardiomyopathy, above-average alcohol consumption generates an arrhythmogenic substrate which abets the onset of AF. Changes of atrial current densities in terms of an electrical remodeling after sustained short-term ethanol infusion in rabbits as a potential part of HHS pathophysiology were examined in this study. Methods:, Rabbits of the ethanol group (EG) received sustained short-term intravenous alcohol infusion for 120 hours (during infusion period, blood alcohol level did not fall below 158 mg/dl), whereas NaCl 0.9% was infused in the placebo group (PG). Using patch clamp technique in whole-cell mode, atrial current densities were measured and compared between both groups. Results:, Ethanol infusion did not alter current densities of Ito [58.7 ± 5.0 pA/pF (PG, n = 20 cells) vs. 53.9 ± 5.0 pA/pF (EG, n = 24)], Isus [11.3 ± 1.4 pA/pF (PG, n = 20) vs. 10.2 ± 1.0 pA/pF (EG, n = 24)], and IK1 [,1.6 ± 0.3 pA/pF (PG, n = 17) vs. ,2.0 ± 0.3 pA/pF (EG, n = 22)]. However, alcohol infusion resulted in a remarkable reduction of ICa,L current densities [,28.4 ± 1.8 pA/pF (PG, n = 20) vs. ,15.2 ± 1.4 pA/pF (EG, n = 22)] and INa [,75.4 ± 3.6 pA/pF (PG, n = 17) vs. ,35.4 ± 4.4 pA/pF (EG, n = 21)], respectively. Conclusion:, Sustained short-term ethanol infusion in rabbits alters atrial current densities. HHS might be favored by alcohol-induced atrial electrical remodeling. [source] Effects of Alcohol on Polysomnographically Recorded Sleep in Healthy SubjectsALCOHOLISM, Issue 9 2006Bernd Feige Background: After studying the sleep of alcohol-dependent patients at the beginning and over the course of abstinence in earlier studies, our interest in the current study focused on the direct effect of 2 doses of alcohol [0.03 and 0.1% blood alcohol level (BAL)] on healthy sleep. This is the first polysomnographic study testing the impact of 2 doses of alcohol ingestion (thus reflecting "normal" social drinking and alcohol abuse) in a single-blind randomized design in healthy volunteers. The study evaluated a short-term acute drinking period for 3 and 2 days of withdrawal from alcohol not only for polysomnographic variables but also for subjective estimates of sleep quality. Methods: In a crossover design with a 1-week interval, healthy subjects received alcohol to raise their blood alcohol to either 0.03 or 0.1% BAL at bedtime for 3 consecutive nights after an alcohol-free baseline night. Objective (polysomnography) and subjective sleep (questionnaires) was recorded each night. During the following 2 days, alcohol was discontinued with simultaneous measurements of sleep to gauge withdrawal effects. Results: At a dose of alcohol leading to BAL of 0.03%, no clear effects could be detected. Following an evening BAL of 0.1%, a hypnotic-like effect (shortened sleep latency, reduced number of wake periods, decreased stage 1 sleep) occurred primarily during the first half of the night with signs of rebound effects being already present during the second half of the night (increased stage 1 sleep). At this dose, alcohol significantly increased slow-wave sleep (SWS) in the first half of the night and reduced REM density in the beginning of the night. After discontinuation of the higher alcohol dose, REM sleep amount increased. No significant withdrawal or rebound effects could be observed for parameters of sleep continuity during the 2 nights after discontinuation from alcohol at a BAL of 0.1%. Conclusions: Owing to the small sample size, the results of this study need to be interpreted with caution. Short-term moderate alcohol consumption (BAL 0.03%) did not significantly alter objective or subjective parameters of sleep. Higher doses of alcohol resulting in a BAL level of 0.10% immediately before going to bed mainly influenced sleep in the first half of the night, resembling the effects of a short-acting hypnotic drug, including a suppression of phasic aspects of REM sleep (REM density). Interestingly, analysis of the latter part of these nights indicated the immediate presence of withdrawal effects (increased light sleep). No statistically significant effects on sleep parameters were observable during the 2 nights of withdrawal from alcohol at the higher BAL. Interpreted carefully, our data indicate that negative effects on sleep occur already with short-term use of alcohol at doses of BAL of 0.10%, despite hypnotic-like effects during the first hours of sleep, especially during the latter part of the night. [source] Anti-Interleukin-6 Antibody Treatment Restores Cell-Mediated Immune Function in Mice With Acute Ethanol Exposure Before Burn TraumaALCOHOLISM, Issue 9 2000Christine V. Fontanilla Background: Previous studies from this laboratory reported that suppression of cell-mediated immune function was coincident with elevated interleukin (IL)-6 production after acute ethanol exposure before burn trauma, compared with either insult alone. The goal of this study was to investigate whether treatment with an anti-IL-6 antibody could restore immunocompetence in mice subjected to burn trauma with previous exposure to alcohol, as assessed by delayed-type hypersensitivity (DTH) and mitogen-induced splenocyte proliferative responses. Methods: Mice given an ethanol treatment designed to reach a blood alcohol level of 100 mg/dl before a 15% total body surface area burn injury were treated with an anti-IL-6 antibody at 30 min and 24 hr postinjury. Results: Burn/ethanol mice exhibited a 91% suppression of the DTH response (p < 0.01) and a 76% suppression of mitogen-induced splenocyte proliferation (p < 0.01) at 48 hr postinjury, along with increased levels of circulating and splenic macrophage-derived IL-6, compared with all other treatment groups. After anti-IL-6 antibody administration to burn/ethanol mice, there was a 25% (p < 0.05) and 63% (p < 0.01) recovery of the DTH and splenocyte proliferative responses, respectively. Addition of exogenous IL-6 to splenocyte cultures isolated from anti-IL-6 antibody-treated burn/ethanol mice resulted in a 70% inhibition of mitogen-induced proliferative responses (p < 0.03). Conclusions: These data confirm previous findings that burn in combination with acute ethanol exposure suppresses cell-mediated immune function compared with either insult alone. Furthermore, the ability of the anti-IL-6 antibody treatment to improve cellular immune responses in the burn/ethanol group suggests that blocking this cytokine may be beneficial for the ethanol-exposed, thermally injured individual. [source] The impact of later trading hours for hotels on levels of impaired driver road crashes and driver breath alcohol levelsADDICTION, Issue 9 2006Tanya Chikritzhs ABSTRACT Aim To examine the impact of later trading hours for licensed hotels in Perth, Western Australia on levels of associated impaired driver road crashes and driver breath alcohol levels (BALs). Design Police data on the ,last place of drinking' for impaired drivers involved in road crashes and their corresponding BALs were examined to identify those associated with Perth hotels between 1 July 1990 and 30 June 1997. During this period, 43 (23%) of the 186 hotels meeting study criteria were granted an Extended Trading Permit for 1 a.m. closing (ETP hotels), while the rest continued to close at midnight (non-ETP hotels). Time-series analyses employing multiple linear regressions were applied to determine whether an association existed between the introduction of extended trading and (i) monthly levels of impaired driver road crashes associated with ETP hotels and (ii) driver BALs associated with ETP hotels. Trends associated with non-ETP hotels were included as controls and possible confounders were considered. Findings After controlling for the trend in crash rates associated with non-ETP hotels and the introduction of mobile police breath testing stations to Perth freeways, a significant increase in monthly crash rates for ETP hotels was found. This relationship was largely accounted for by higher volumes of high-alcohol content beer, wine and spirits purchased by ETP hotels. No relation was found between driver BALs and the introduction of ETPs. Conclusions Late trading was associated with increased levels of impaired driver road crashes and alcohol consumption, particularly high-risk alcoholic beverages. Greater numbers of patrons and characteristics specific to clientele of hotels which applied for late trading hours (i.e. younger age, greater propensity to drunk-drive, preference for high-risk beverages) were suggested as having contributed to this increase. [source] REVIEW: Ethanol consumption: how should we measure it?ADDICTION BIOLOGY, Issue 2 2010Achieving consilience between human, animal phenotypes ABSTRACT There is only modest overlap in the most common alcohol consumption phenotypes measured in animal studies and those typically studied in humans. To address this issue, we identified a number of alcohol consumption phenotypes of importance to the field that have potential for consilience between human and animal models. These phenotypes can be broken down into three categories: (1) abstinence/the decision to drink or abstain; (2) the actual amount of alcohol consumed; and (3) heavy drinking. A number of suggestions for human and animal researchers are made in order to address these phenotypes and enhance consilience. Laboratory studies of the decision to drink or to abstain are needed in both human and animal research. In human laboratory studies, heavy or binge drinking that meets cut-offs used in epidemiological and clinical studies should be reported. Greater attention to patterns of drinking over time is needed in both animal and human studies. Individual differences pertaining to all consumption phenotypes should be addressed in animal research. Lastly, improved biomarkers need to be developed in future research for use with both humans and animals. Greater precision in estimating blood alcohol levels in the field, together with consistent measurement of breath/blood alcohol levels in human laboratory and animal studies, provides one means of achieving greater consilience of alcohol consumption phenotypes. [source] Impaired fear conditioning but enhanced seizure sensitivity in rats given repeated experience of withdrawal from alcoholEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2001D. N. Stephens Abstract Repeated experience of withdrawal from chronic alcohol treatment increases sensitivity to seizures. It has been argued by analogy that negative affective consequences of withdrawal also sensitize, but repeated experience of withdrawal from another sedative-hypnotic drug, diazepam, results in amelioration of withdrawal anxiety and aversiveness. We tested whether giving rats repeated experience of withdrawal from alcohol altered their ability to acquire a conditioned emotional response (CER). Male Hooded Lister rats were fed a nutritionally complete liquid diet as their only food source. Different groups received control diet, or diet containing 7% ethanol. Rats receiving ethanol diet were fed for either 24 days (Single withdrawal, SWD), or 30 days, with two periods of 3 days, starting at day 11, and 21, in which they received control diet (Repeated withdrawal, RWD). All rats were fed lab chow at the end of their liquid diet feeding period. Starting 12 days after the final withdrawal, groups of Control, SWD and RWD rats were given pentylenetetrazole (PTZ; 30 mg/kg, i.p.) three times a week, and scored for seizures. The occurrence of two successive Stage 5 seizures was taken as the criterion for full PTZ kindling. Other groups of control, SWD and RWD rats were trained to operate levers to obtain food, and were then exposed, in a fully counterbalanced design, to light and tone stimuli which predicted unavoidable footshock (CS+), or which had no consequences (CS,). Rats consumed approximately 17.5 g/kg/day of ethanol, resulting in blood alcohol levels of approximately 100 mg/dL. Repeated administration of PTZ resulted in increasing seizure scores. RWD rats achieved kindling criterion faster than either Control or SWD rats. No differences were seen in the groups in flinch threshold to footshock (0.3 mA). At a shock intensity of 0.35 mA, Control, but not RWD or SWD rats showed significant suppression to the CS+ CS, presentation did not affect response rates. The three groups differed in their response to pairing the CS+ with increasing shock levels, the Controls remaining more sensitive to the CS+. SWD rats showed significant suppression of lever pressing during CS+ presentations only at 0.45 and 0.5 mA, and RWD rats only at 0.5 mA. Giving rats repeated experience of withdrawal from chronic ethanol results in increased sensitivity to PTZ kindling, but reduces their ability to acquire a CER. Withdrawal kindling of sensitivity to anxiogenic events does not seem to occur under circumstances which give rise to kindling of seizure sensitivity. [source] Revisiting Intragastric Ethanol Intubation as a Dependence Induction Method for Studies of Ethanol Reward and Motivation in RatsALCOHOLISM, Issue 3 2010Simone Braconi Background:, The purpose of this study was to re-examine intragastric ethanol intubation as a dependence induction method that effectively induces physical dependence upon ethanol over a short time period, is devoid of intrinsic stress artifacts, inexpensive, and easy to implement. Methods:, Male Wistar rats were subjected to ethanol dependence induction via intragastric ethanol intubation. Ethanol solution (final concentration 20%, made up in a dietary liquid vehicle consisting of powdered milk, sucrose, and water) was intubated 4 times per day, at 4-hour intervals, for 6 consecutive days (for a total of 10 g/kg/day). The utility of this procedure was evaluated for inducing physical dependence, determined by daily and final withdrawal ratings. Anxiety-like behavior associated with ethanol dependence history was examined using the elevated plus-maze (EPM) test, conducted 5 days after ethanol withdrawal. To evaluate whether potential stress-like effects of intragastric intubation per se produce lasting effects on behavior, experimentally naive rats were compared with vehicle-intubated rats for anxiety-like behavior on the EPM. Results:, Blood alcohol levels reached stable levels between 200 and 250 mg%, measured 1 hour after the second and third ethanol intubation on days 2, 4, and 6. Ethanol-treated rats developed significant somatic withdrawal signs, recorded daily between 10 and 12 hours after the last ethanol administration. At 5 days postwithdrawal, ethanol-treated rats showed significant anxiety-like behavior, measured by decreased open arm time and open arm entries on the EPM, compared with vehicle controls. Additionally, ethanol postdependent rats showed decreased open arm time compared with experimentally naive rats. EPM performance did not differ between vehicle-intubated and naive rats. No withdrawal seizures were observed and mortality rate was near zero. Conclusions:, These findings suggest that intragastric ethanol administration produces a behavioral profile consistent with ethanol dependence (i.e., significant withdrawal signs after termination of ethanol exposure and elevated anxiety-like behavior persisting beyond completion of physical withdrawal), and that the intubation procedure itself does not produce lasting nonspecific anxiety-like effects. Thus, under the conditions employed here, this procedure provides an effective tool for inducing and evaluating the consequences of ethanol dependence in animal models of ethanol reward and motivation. [source] Alcohol Biomarkers in Patients Admitted for TraumaALCOHOLISM, Issue 10 2009Michael Fleming Background:, To assess the value of blood alcohol levels (BAL) and carbohydrate-deficient transferrin (CDT) in trauma patients. Methods:, A prospective study was conducted among 213 patients admitted to a university hospital after trauma. Outcomes of interest included the development of alcohol withdrawal, infections, respiratory problems, cardiac events, thromboembolism, and length of stay. Results:, The majority (78%) of the trauma patients in the study was males over the age of 18. Seventy-five percent were reported drinking an alcohol-containing beverage in the previous 30 days, 34% had ,5 heavy drinking days, and 18.7% met current DSM-IV criteria for alcohol abuse and 13.1% current criteria for dependence. Twenty-two percent (n = 48) had a positive BAL and 14% (n = 30) a CDT level >2.5%. Twelve percent (n = 27) of the sample developed alcohol withdrawal and 55% (n = 113) had one or more adverse health events during their hospitalization. The development of alcohol withdrawal was associated with an admission CDT >2.5% (,2: 4.77, p < 0.029) and/or a positive BAL (,2: 54.01, p < 0.001). The alcohol biomarkers identified 13 male and 3 female high-risk patients (7.4% of the total sample) who denied excessive alcohol use, and who would have been missed if these markers were not used. A composite morbidity trauma score composed of 25 adverse health events was associated with a positive BAL (p < 0.022). Conclusion:, The study provides additional empirical evidence that supports the use of BAL in all patients admitted for trauma. The usefulness of CDT in trauma patients remains unclear and will require larger samples in more critically ill patients. [source] A Double-Blind Trial of Gabapentin Versus Lorazepam in the Treatment of Alcohol WithdrawalALCOHOLISM, Issue 9 2009Hugh Myrick Introduction:, Some anticonvulsants ameliorate signs and symptoms of alcohol withdrawal, but have an unacceptable side effect burden. Among the advantages of using anticonvulsant agents in this capacity is their purported lack of interaction with alcohol that could increase psychomotor deficits, increase cognitive impairment, or increase intoxication. The aim of this study was to evaluate alcohol use and symptom reduction of gabapentin when compared with lorazepam in the treatment of alcohol withdrawal in a double-blinded randomized clinical trial. Methods:, One hundred individuals seeking outpatient treatment of alcohol withdrawal with Clinical Institute Withdrawal Assessment for Alcohol,Revised (CIWA-Ar) ratings ,10 were randomized to double-blind treatment with 2 doses of gabapentin (900 mg tapering to 600 mg or 1200 tapering to 800 mg) or lorazepam (6 mg tapering to 4 mg) for 4 days. Severity of alcohol withdrawal was measured by the CIWA-Ar on days 1 to 4 of treatment and on days 5, 7, and 12 post-treatment and alcohol use monitored by verbal report and breath alcohol levels. Results:, CIWA-Ar scores decreased over time in all groups; high-dose gabapentin was statistically superior but clinically similar to lorazepam (p = 0.009). During treatment, lorazepam-treated participants had higher probabilities of drinking on the first day of dose decrease (day 2) and the second day off medication (day 6) compared to gabapentin-treated participants (p = 0.0002). Post-treatment, gabapentin-treated participants had less probability of drinking during the follow-up post-treatment period (p = 0.2 for 900 mg and p = 0.3 for 1200 mg) compared to the lorazepam-treated participants (p = 0.55). The gabapentin groups also had less craving, anxiety, and sedation compared to lorazepam. Conclusions:, Gabapentin was well tolerated and effectively diminished the symptoms of alcohol withdrawal in our population especially at the higher target dose (1200 mg) used in this study. Gabapentin reduced the probability of drinking during alcohol withdrawal and in the immediate postwithdrawal week compared to lorazepam. [source] The Overlap in Predicting Alcohol Outcome for Two Measures of the Level of Response to AlcoholALCOHOLISM, Issue 3 2009Marc A. Schuckit Background:, Two different measures have been used to establish a person's level of response (LR) to alcohol as a risk factor for alcohol use disorders. LR values established by the alcohol challenge protocol and the Self-Report of the Effects of Ethanol (SRE) questionnaire usually correlate at 0.3 to 0.4, up to 0.6. However, it is not clear how this correlation relates to the ability of each measure to predict alcohol outcomes. This paper evaluates that overlap. Methods:, Sixty-six Caucasian males (mean age = 22 years) from 2 protocols participated in alcohol challenges with 0.75 ml/kg of ethanol, filled out the SRE, and were followed with a structured interview ,5 years later. The relationship between the subjective feelings of intoxication at the time of peak breath alcohol levels from the alcohol challenge and the SRE score for a time early in the drinking career were evaluated regarding predicting the drinks per occasion in the 6 months prior to follow-up. Results:, Cross-sectional correlations between alcohol challenge and SRE LR's ranged from ,0.25 (p < 0.05) to ,0.32 (p = 0.02) for the full sample, and the 2 LR measures correlated with drinking at follow-up (,0.26 and 0.41, respectively). The SRE measure was more robust than the challenge in a regression analysis predicting the outcome in the context of other baseline predictors (e.g., drinking at baseline). As much as 60% of the ability of the more well established (gold standard) alcohol challenge LR to predict outcome was shared with the SRE. The alcohol challenge accounted for as much as 44% of the ability of the SRE to predict outcome. Conclusions:, The SRE-generated LR overlapped considerably with the alcohol challenge LR in the ability to predict future heavier drinking. [source] Alcohol in Moderation, Cardioprotection, and Neuroprotection: Epidemiological Considerations and Mechanistic StudiesALCOHOLISM, Issue 2 2009Michael A. Collins In contrast to many years of important research and clinical attention to the pathological effects of alcohol (ethanol) abuse, the past several decades have seen the publication of a number of peer-reviewed studies indicating the beneficial effects of light-moderate, nonbinge consumption of varied alcoholic beverages, as well as experimental demonstrations that moderate alcohol exposure can initiate typically cytoprotective mechanisms. A considerable body of epidemiology associates moderate alcohol consumption with significantly reduced risks of coronary heart disease and, albeit currently a less robust relationship, cerebrovascular (ischemic) stroke. Experimental studies with experimental rodent models and cultures (cardiac myocytes, endothelial cells) indicate that moderate alcohol exposure can promote anti-inflammatory processes involving adenosine receptors, protein kinase C (PKC), nitric oxide synthase, heat shock proteins, and others which could underlie cardioprotection. Also, brain functional comparisons between older moderate alcohol consumers and nondrinkers have received more recent epidemiological study. In over half of nearly 45 reports since the early 1990s, significantly reduced risks of cognitive loss or dementia in moderate, nonbinge consumers of alcohol (wine, beer, liquor) have been observed, whereas increased risk has been seen only in a few studies. Physiological explanations for the apparent CNS benefits of moderate consumption have invoked alcohol's cardiovascular and/or hematological effects, but there is also experimental evidence that moderate alcohol levels can exert direct "neuroprotective" actions,pertinent are several studies in vivo and rat brain organotypic cultures, in which antecedent or preconditioning exposure to moderate alcohol neuroprotects against ischemia, endotoxin, ,-amyloid, a toxic protein intimately associated with Alzheimer's, or gp120, the neuroinflammatory HIV-1 envelope protein. The alcohol-dependent neuroprotected state appears linked to activation of signal transduction processes potentially involving reactive oxygen species, several key protein kinases, and increased heat shock proteins. Thus to a certain extent, moderate alcohol exposure appears to trigger analogous mild stress-associated, anti-inflammatory mechanisms in the heart, vasculature, and brain that tend to promote cellular survival pathways. [source] Only Male Mice Show Sensitization of Handling-Induced Convulsions Across Repeated Ethanol Withdrawal CyclesALCOHOLISM, Issue 3 2007L.M. Veatch Background: Alcohol abuse, especially when experienced in multiple cycles of chronic abuse and withdrawal, leads to a sensitization of central nervous system hyperexcitability that may culminate in overt expression of seizures. In spite of the growing prevalence of alcohol abuse and dependence in females shown in recent epidemiologic studies, evidence of sexual dimorphism in the expression of alcohol withdrawal-induced seizures and the development of seizure sensitization following multiple cycles of ethanol (EtOH) exposure and withdrawal has not been examined in either animal models or in clinical reports. Methods: Subjects in these experiments were male and female C3H/Hecr mice. The female mice were intact or ovariectomized, with ovariectomized mice receiving 17- , -estradiol or placebo pellets. All mice were exposed to 4 cycles of exposure to 16-hour EtOH vapor, separated by 8-hour withdrawal periods. During each 8-hour withdrawal, hourly assessment of seizure propensity was assessed as handling-induced convulsions. Additional assessments were taken up to 72 hours after the final EtOH withdrawal cycle. Results: Male and female mice showed similar seizure propensity during an initial withdrawal from chronic EtOH. Across subsequent withdrawal cycles, however, male mice exhibited a robust increase in seizure severity beginning with the third withdrawal cycle. In marked contrast, female mice failed to demonstrate sensitization of seizure severity. The lack of seizure sensitization following up to 4 cycles of alcohol exposure and withdrawal could not be explained by hormonal status (presence or absence of estrogen) or by sex differences in blood alcohol levels. Conclusions: Male and female mice exposed to the same number of cycles of EtOH withdrawal demonstrate differences in expression of seizures. Males show the typical sensitization of seizures, or kindling response, which has been reported clinically as well as in animal models, but females do not. The reason for the lack of seizure sensitization in female mice remains to be elucidated, but may be related to sex differences in alcohol effects on excitatory/inhibitory neurotransmission, rather than to hormonal or blood alcohol level differences. [source] Effects of Alcohol Consumption on Iron Metabolism in Mice with Hemochromatosis MutationsALCOHOLISM, Issue 1 2007Jonathan M. Flanagan Background: Alcoholic liver disease is associated with increased hepatic iron accumulation. The liver-derived peptide hepcidin is the central regulator of iron homeostasis and recent animal studies have demonstrated that exposure to alcohol reduces hepcidin expression. This down-regulation of hepcidin in vivo implies that disturbed iron sensing may contribute to the hepatosiderosis seen in alcoholic liver disease. Alcohol intake is also a major factor in expression of the hemochromatosis phenotype in patients homozygous for the C282Y mutation of the HFE gene. Methods: To assess the effect of alcohol in mice with iron overload, alcohol was administered to mice with disrupted Hfe and IL-6 genes and Tfr2 mutant mice and their respective 129x1/SvJ, C57BL/6J, and AKR/J wild-type congenic strains. Iron absorption, serum iron levels, and hepcidin expression levels were then measured in these mice compared with water-treated control mice. Results: Alcohol was shown to have a strain-specific effect in 129x1/SvJ mice, with treated 129x1/SvJ mice showing a significant increase in iron absorption, serum iron levels, and a corresponding decrease in hepcidin expression. C57BL/6J and AKR/J strain mice showed no effect from alcohol treatment. 129x1/SvJ mice heterozygous or homozygous for the Hfe knockout had a diminished response to alcohol. All 3 strains were shown to have high blood alcohol levels. Conclusions: The effect of alcohol on iron homeostasis is dependent on the genetic background in mice. In an alcohol-susceptible strain, mutation of the Hfe gene diminished the response of the measured iron indices to alcohol treatment. This indicates that either maximal suppression of hepcidin levels had already occurred as a result of the Hfe mutation or that Hfe was a component of the pathway utilized by EtOH in suppressing hepcidin production and increasing iron absorption. [source] Gelatin "Shots" as a New Method for Alcohol Administration in a Laboratory SettingALCOHOLISM, Issue 3 2006Elizabeth Ralevski Background: This experiment was designed to compare gelatin "shots",a new procedure for administering alcohol in a laboratory setting,to the alcohol beverage method. We proceeded to test whether the two methods were comparable in terms of alcohol absorption, metabolism, and effects on mood and whether gelatin "shots" were better than the beverage in disguising alcohol in a blind, placebo comparison. Methods: Healthy volunteers participated in a two-phase trial. In the first phase they completed 2 days of testing during which the effects of alcohol,delivered in beverage (1 day) or gelatin "shots" (alternative day),on blood and breathalyzer concentrations and mood were assessed. In the second phase participants completed 2 days of testing and were asked to identify if samples contained alcohol or placebo. The presentation of alcohol and placebo and the presentation of beverage or gelatin "shots" were random. Results: In the first phase there was a significant time-by-condition interaction in the blood alcohol concentration. Two-and-a-half hours after the alcohol was administered, those given gelatin "shots" had slightly lower but statistically significant blood alcohol concentrations. There was a significant time effect for breathalyzer alcohol levels but no condition or condition-by-time interaction. There were no differences between the two methods on any of the subjective mood measures. In the second phase of the study there were differences in the ability to differentiate alcohol from placebo between the two conditions with significantly more participants making errors in the gelatin "shots" than in the beverage condition. Conclusions: Our findings indicate that gelatin "shots" are an effective method for delivering alcohol to humans in a laboratory setting. This method may be superior to the alcohol beverage mixture in a placebo-controlled design because gelatin "shots" mask the alcohol much better than a beverage and are easier to administer. [source] Enhanced Prepulse Inhibition Following Adolescent Ethanol Exposure in Sprague-Dawley RatsALCOHOLISM, Issue 10 2005Craig J. Slawecki Abstract: Objectives: Recent studies have demonstrated that ethanol exposure differentially affects adolescents and adults. The current studies were designed to compare the effects of 2-week exposure to ethanol during adolescence or adulthood on the acoustic startle response (ASR) and prepulse inhibition (PPI) Methods: Male Sprague-Dawley rats were exposed to ethanol vapor 12 hr/d (on from 6 pm to 6 am) for 14 days during adolescence or adulthood. Six days after the cessation of ethanol vapor exposure, the ASR and PPI were assessed. Results: During ethanol treatment, overall blood alcohol levels averaged 230 to 250 mg/dl in the adolescent and adult treatment groups. Assessment of the ASR revealed that latency to startle was more rapid in adolescents than in adults, but ASR latency was not altered by ethanol exposure. In addition, ASR magnitude was lower in adolescents and was decreased in ethanol-exposed rats on startle trials. Ethanol exposure significantly enhanced PPI, but only after adolescent exposure Conclusions: These data further demonstrate a differential sensitivity of adolescents and adults to the effects of ethanol exposure. Specifically, a 2-week period of ethanol exposure during adolescence selectively enhanced PPI, a neurobehavioral index of sensorimotor gating. However, ASR magnitude was decreased by ethanol exposure regardless of age. On the basis of previous studies, the effects of ethanol exposure on PPI data could indicate that adolescent rats exposed to ethanol are more likely to exhibit behavioral inflexibility and that ethanol exposure acts as a more potent physical stressor in adolescent rats. [source] Does an Energy Drink Modify the Effects of Alcohol in a Maximal Effort Test?ALCOHOLISM, Issue 9 2004Sionaldo Eduardo Ferreira Background: There are popular reports on the combined use of alcohol and energy drinks (such as Red Bull® and similar beverages, which contain caffeine, taurine, carbohydrates, etc.) to reduce the depressant effects of alcohol on central nervous system, but no controlled studies have been performed. The main purpose of this study was to verify the effects of alcohol, and alcohol combined with energy drink, on the performance of volunteers in a maximal effort test (cycle ergometer) and also on physiological indicators (oxygen uptake, ventilatory threshold, respiratory exchange rate, heart rate, and blood pressure), biochemical variables (glucose, lactate, insulin, cortisol, ACTH, dopamine, noradrenaline, and adrenaline), and blood alcohol levels. Methods: Fourteen healthy subjects completed a double-blind protocol made up of four sessions: control (water), alcohol (1.0 g/kg), energy drink (3.57 ml/kg Red Bull®), and alcohol + energy drink, each 1 week apart. The effort test began 60 min after drug or control ingestion, and the dependent variables were measured until 60 min after the test. Results: Heart rate at the ventilatory threshold was higher in the alcohol and alcohol + energy drink sessions in comparison with control and energy drink sessions. Although in comparison to the control session, the peak oxygen uptake was 5.0% smaller after alcohol ingestion, 1.4% smaller after energy drink, and 2.7% smaller after the combined ingestion, no significant differences were detected. Lactate levels (30 min after drug ingestion, 30 and 60 min after the effort test) and noradrenaline levels (30 min after the effort test) were higher in the alcohol and alcohol + energy drink sessions compared with the control session. Conclusions: The performance in the maximal effort test observed after alcohol + energy drink ingestion was similar to that observed after alcohol only. No significant differences between alcohol and alcohol + energy drink were detected in the physiological and biochemical parameters analyzed. Our findings suggest that energy drinks, at least in the tested doses, did not improve performance or reduce alterations induced by acute alcohol ingestion. [source] A Mouse Model of Prenatal Ethanol Exposure Using a Voluntary Drinking ParadigmALCOHOLISM, Issue 12 2003Andrea M. Allan Background: The incidence of fetal alcohol spectrum disorders is estimated to be as high as 1 in 100 births. Efforts to better understand the basis of prenatal ethanol-induced impairments in brain functioning, and the mechanisms by which ethanol produces these defects, will rely on the use of animal models of fetal alcohol exposure (FAE). Methods: Using a saccharin-sweetened alcohol solution, we developed a free-choice, moderate alcohol access model of prenatal alcohol exposure. Stable drinking of a saccharin solution (0.066%) was established in female mice. Ethanol then was added to the saccharin in increasing concentrations (2%, 5%, 10% w/v) every 2 days. Water was always available, and mice consumed standard pellet chow. Control mice drank saccharin solution without ethanol. After a stable baseline of ethanol consumption (14 g/kg/day) was obtained, females were impregnated. Ethanol consumption continued throughout pregnancy and then was decreased to 0% in a step-wise fashion over a period of 6 days after pups were delivered. Characterization of the model included measurements of maternal drinking patterns, blood alcohol levels, food consumption, litter size, pup weight, pup retrieval times for the dams, and effects of FAE on performance in fear-conditioned learning and novelty exploration. Results: Maternal food consumption, maternal care, and litter size and number were all found to be similar for the alcohol-exposed and saccharin control animals. FAE did not alter locomotor activity in an open field but did increase the time spent inspecting a novel object introduced into the open field. FAE mice displayed reduced contextual fear when trained using a delay fear conditioning procedure. Conclusions: The mouse model should be a useful tool in testing hypotheses about the neural mechanisms underlying the learning deficits present in fetal alcohol spectrum disorders. Moreover, a mouse prenatal ethanol model should increase the opportunity to use the power of genetically defined and genetically altered mouse populations. [source] Disruption of Maternal Behavior by Alcohol Intoxication in the Lactating Rat: A Behavioral and Metabolic AnalysisALCOHOLISM, Issue 8 2002Marta Yanina Pepino Background 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. Methods 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. Results 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). Conclusions 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. [source] Biological Markers of Alcohol Consumption in Nondrinkers, Drinkers, and Alcohol-Dependent Brazilian PatientsALCOHOLISM, Issue 7 2002N. B. Figlie Background The purpose of this study was to compare the sensitivity and specificity of some new and traditional biological markers and indicators of health among Brazilian nondrinkers, drinkers, and alcohol-dependent patients. Material and Methods We evaluated 130 nondrinkers, 167 drinkers, and 183 alcohol-dependent drinkers from Brazil who participated in the WHO/ISBRA Study on State and Trait Markers of Alcohol Use and Dependence. A standardized WHO/ISBRA Interview Schedule provided background information on the subjects' characteristics including reported health problems and alcohol consumption. Blood samples were analyzed for aspartate aminotransferase (AST), carbohydrate deficient transferrin (CDT), ,-glutamyltransferase (GGT), blood alcohol levels (BAL), and platelet adenylate cyclase activity (basal levels [AC] and levels after stimulation with Gpp(NH)p, cesium fluoride, and forskolin). Results The alcohol-dependent drinkers presented higher levels of AST, GGT, AC, CDT, and BAL than the nondrinkers and drinkers, whose levels were similar. Sex differences in the sensitivity of CDT and AC were found. The alcohol-dependent women presented a lower prevalence of abnormal values of CDT and Gpp(NH)p-stimulated AC than the alcohol-dependent men, despite the fact that they presented similar alcohol consumption levels. The alcohol-dependent drinkers presented a higher prevalence of clinical disorders than the nondrinkers and drinkers. The drinkers and alcohol-dependent patients presented significantly higher rates of gastritis than the nondrinkers. Conclusions Sex differences in the sensitivity of CDT and AC suggest that these markers are not as sensitive at detecting excessive alcohol use in women as they are in men. If data from this Brazilian sample are compared with those reported for international samples, relevant differences are detected, which suggests that genetic and cultural differences should be considered in the selection of biological markers of heavy alcohol consumption. [source] Acute, Rapid, and Chronic Tolerance During Ontogeny: Observations When Equating Ethanol Perturbation Across AgeALCOHOLISM, Issue 9 2001Marisa M. Silveri Background: Sensitivity to the motor-impairing and hypnotic effects of ethanol (EtOH) increases notably during development. Less is known, however, about the ontogeny of EtOH tolerance and the ontogenetic relationship among different types of tolerance. Consequently, we compared the ontogenetic development of acute, rapid, and chronic tolerance to EtOH-induced motor impairment and hypothermia in a swim task. Methods: Preweanling, adolescent, and adult female and male Sprague-Dawley rats were given chronic saline (control group), five daily EtOH exposures before EtOH on test day (chronic group), one EtOH exposure before test day (rapid group), or EtOH exposure only on test day (acute groups). Separate groups of animals in the acute groups were tested at 15, 60, or 105 min after injection to estimate acute tolerance development via calculating slopes of the linear regression of impairment relative to brain alcohol levels at each postinjection interval. Initial EtOH perturbation of swim performance was equated across age by varying EtOH dose. Results: Acute tolerance was evident to the motor-impairing effects of EtOH at all ages. When impairment was indexed relative to brain alcohol levels, rapid and chronic tolerance to the motor-impairing effects of EtOH on latency to reach the start was seen across age, although this tolerance tended to be more pronounced in adults. Somewhat different ontogenetic patterns of tolerance development were observed with EtOH-induced hypothermia, a dependent measure for which EtOH perturbation was not equated across age. Conclusions: The degree of initial perturbation by EtOH seems to be an important predictor of tolerance expression during ontogeny. That is, ontogenetic profiles of tolerance development differ significantly when EtOH-induced motor impairment is equated across age rather than dose of EtOH administered . The role of target response measures and context stress should also be considered when exploring ontogenetic expression of EtOH tolerance. [source] Early Alteration in Leukocyte Populations and Th1/Th2 Function in Ethanol-Consuming MiceALCOHOLISM, Issue 8 2001Shawn Starkenburg Background: Chronic alcohol consumption polarizes the immune response away from Th1-mediated cell-mediated immunity. In the present report we investigate the first onset of alteration in immune parameters during ethanol consumption in terms of changes in splenic leukocyte cellularity and surface phenotype as well as alterations in Th1 and Th2 function. Methods: BALB/c and C57BL/6 mice were fed ethanol-containing liquid diets, were pair-fed an isocaloric liquid control diet, or were fed solid diet and water ad libitum for up to 12 days. At intervals during the feeding period, splenic leukocytes were assessed for phenotypic markers by flow cytometry and for their ability to support antigen-induced interferon-, (IFN,) production in a coculture system. Mice were bled at intervals throughout the feeding period, and serum immunoglobin E (IgE) and alcohol levels were determined. Results: Data show that phenotypic and functional alterations occur within the first few days of alcohol consumption. Both liquid diets affect splenic cellularity, and by dietary day 5, ethanol-containing liquid diets further reduce B and NK cell numbers. The decline in B cells is accompanied by a concomitant decline in the amount of major histocompatibility complex class II expressed on this population. Functional alteration in Th1-mediated IFN, production occurred in the population fed ethanol-containing liquid diets by dietary day 5. Th2 function, as indicated by systemic serum IgE levels in these unimmunized mice, is increased by dietary day 6 to 8 and correlated with significant blood alcohol levels. Conclusions: Ethanol consumption by mice causes a rapid decrease in splenic cellularity accompanied by a decrease in Th1 function and a rapid increase in systemic IgE levels. [source] Influence of chronic alcohol abuse and ensuing forced abstinence on static subjective accommodation function in humansOPHTHALMIC AND PHYSIOLOGICAL OPTICS, Issue 3 2001Hugh Campbell Summary Purpose. Acute alcohol ingestion can change accommodation, but the long term effects of sustained alcohol consumption on accommodative function have not been studied in detail. This study was thus undertaken on individuals with a history of alcohol abuse. Methods. Thirty-seven male individuals aged 25,56 years (average 40 years) from an alcohol rehabilitation centre in Inverness, Scotland, were assessed on admission and after a week of forced abstinence. The results were compared to a paired age-matched set of control male subjects. The static amplitude of accommodation was measured by an RAF rule, and the pupil size measured with a pupil gauge. Results. On admission, the group mean measured amplitude of accommodation was 4.7±2.2 D (mean±SD). These values for the alcoholics were lower than age-matched controls (of5.9±2.9 D). The slope of the age-dependent decline in RAF rule accommodation measures was significantly smaller for the alcoholics compared to controls (at 0.215±0.027 D/year versus0.332±0.015 D/year, respectively; p <0.001), with the younger alcoholics showing a greater impairment. Following abstinence, there was no measurable change in accommodation measured, indicating the lower amplitude in the alcoholics was not attributable to circulatory alcohol levels. The resting pupil diameter in the alcoholics was4.37±0.63 mm compared to the controls of3.97±0.75 mm, with a higher incidence of small pupils (,3 mm) in the controls. Conclusions. The results indicate that chronic alcohol use can adversely affect subjective static accommodation, especially in younger alcoholics, as well as cause slight mydriasis. [source] Composition of alkyl esters in the cuticular wax on inflorescence stems of Arabidopsis thaliana cer mutantsTHE PLANT JOURNAL, Issue 2 2007Christine Lai Abstract Wax biosynthetic pathways proceed via the elongation of 16:0 acyl-CoA to very long-chain fatty acids (VLCFA), and by further modifications that include reduction to primary alcohols and formation of alkyl esters. We have analyzed the alkyl esters in the stem wax of ten cer mutants of Arabidopsis thaliana together with the corresponding wild types. Alkyl esters with chain lengths between C38 and C52 were identified, and the levels of esters ranged from 0.15 µg cm,2 in Wassilewskija (WS) to 1.20 µg cm,2 in cer2. Esters with even numbers of carbons prevailed, with C42, C44 and C46 favoured in the wild types, a predominance of C42 in cer2 and cer6 mutants, and a relative shift towards C46 in cer3 and cer23 mutants. The esters of all mutants and wild types were dominated by 16:0 acyl moieties, whereas the chain lengths of esterified alcohols were between C20 and C32. The alkyl chain-length distributions of the wild-type esters had a maximum for C28 alcohol, similar to the free alcohols accompanying them in the wax mixtures. The esterified alcohols of cer2, cer6 and cer9 had largely increased levels of C26 alcohol, closely matching the patterns of the corresponding free alcohols and, therefore, differing drastically from the corresponding wild type. In contrast, cer1, cer3, cer10, cer13 and cer22 showed ester alcohol patterns with increased levels of C30, only partially following the shift in chain lengths of the free alcohols in stem wax. These results provide information on the composition of substrate pools and/or the specificity of the ester synthase involved in wax ester formation. We conclude that alcohol levels at the site of biosynthesis are mainly limiting the ester formation in the Arabidopsis wild-type epidermis. [source] | |||||||||||||