bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatic Stellate Cells and Liver Retinoid Content in Alcoholic Liver Disease in Humans
Authors: Hautekeete Marc Leopold , Dodeman Isabelle , Azais‐Braesco Véronique , Van den Berg Kit , Seynaeve Carine , Geerts Albert
Published: May 2006

Body retinoids are stored in the lipid droplets of hepatic stellate (Ito) cells. In chronic liver disease, the stellate cells differentiate into myo‐fibroblast‐like cells, a process whereby they lose their retinoid‐con‐taining lipid droplets. We studied the relation between liver retinoid content, the number of lipid droplets per stellate cell, and the number of stellate cells per mm2 in human alcoholic liver disease. Semithin sections of liver biopsies from normal subjects and patients with early (steatosis, inflammation, and mild fibrosis) and late (cirrhosis and cirrhosis with acute alcoholic hepatitis) alcoholic liver disease were morphometrically evaluated. Liver retinoid content was determined by HPLC. In normal patients, liver retinoid content was 901 ± 213 lU/g of liver (mean ± SEM). There was a decrease in liver retinoid content in early alcoholic liver disease (409 ± 50 IU/g) and a further reduction in cirrhosis (153 ± 50 IU/g). In patients with acute alcoholic hepatitis, retinoid content was strikingly low (5.2 ± 1.8 IU/g). There was a progressive decrease in the number of stellate cells per mm2 associated with progressive liver damage. We found a fair correlation between the number of stellate cells per mm2 and liver retinoid content in all patient groups (overall correlation: 0.71). In normal subjects, the mean number of lipid droplets per stellate cell was 7.4 ± 0.7. In patients with early alcoholic liver disease and in patients with alcoholic cirrhosis, this value was increased to 13.6 ± 0.8 and 10.4 ± 2.0, respectively. In patients with acute alcoholic hepatitis, only a few lipid droplets were present (4.2 ± 0.5). There was a good correlation between liver retinoid content and mean number of lipid droplets in normal patients (r= 0.58). In alcoholic cirrhosis, however, correlation was poor (r= 0.34). In early alcoholic liver disease, the correlation was absent (r= 0.004). In conclusion, the major finding of our study is that the correlation between the mean number of lipid droplets per stellate cell and liver retinoid content varies according to the hepatic pathology considered. Marked lipid droplet accumulation occurs in stellate cells in early alcoholic liver disease and, to a lesser extent, in alcoholic cirrhosis, but there is no correlation between the mean number of lipid droplets per stellate cell and liver retinoid content. Therefore, not retinoids but probably lipids are responsible for the accumulation of lipid droplets. We also find that there is a fair correlation between the number of stellate cells per mm2 and liver retinoid content in all patient groups. Finally, we confirm the decrease in hepatic retinoid content that occurs in alcoholic liver disease in humans, even at the early stages of the disease.
Inducibility of Cytochromes P‐4502E1 and P‐4501A1 in the Rat Pancreas
Authors: Kessova Irina G. , DeCarli Leonore M. , Lieber Charles S.
Published: May 2006

Cytochrome P‐450 (CYP) isoenzymes have been incriminated in the toxicity and carcinogenicity of various xenobiotics in different tissues, but prior measurements of their activity in pancreatic microsomes have been disappointing. We now applied new isolation methods and a highly sensitive procedure to assay for the metabolism of p‐nitrophenol and 7‐ethoxyresorufin, specific substrates for CYP2E1 (2E1) and CYP1A1 (1A1), respectively. 2E1 and 1A1 content was estimated with high‐resolution chemiluminescent Western blots using recombinant 2E1 and 1A1 as standards. We found that p‐nitrophenol hydroxylase activity was 5.07 ± 0.66 and 1.50 ± 0.26 pmol/ min/mg of protein in pancreatic microsomes of ethanol‐fed and control rats, respectively. Chronic ethanol treatment increased 2E1 content in pancreatic microsomes 3.6‐fold. Activity and content of 2E1 were also assessed in hepatic microsomes: specific activity (expressed per 2E1 content) was similar in pancreatic and hepatic microsomes. There was also an inductive effect of 3‐methylcholan‐threne (MC) on 1A1 in pancreatic microsomes. Pancreatic microsomal 7‐ethoxyresorufin‐O‐dealkylation activity in MC‐treated rats was 19.6 ± 1.7 pmol/min/mg of protein, 61‐fold higher than in controls. MC treatment increased the 1A1 content in pancreatic microsomes 42‐fold. These results demonstrate that, in pancreatic microsomes, ethanol and MC exert striking inductive effects on 2E1 and 1A1 activities, which could play a role in the pathogenesis of pancreatitis and/or pancreatic cancer.
A Family‐Based Analysis of the Association of the Dopamine D2 Receptor (DRD2) with Alcoholism
Authors: Edenberg Howard J. , Foroud Tatiana , Koller Daniel L. , Goate Alison , Rice John , Van Eerdewegh Paul , Reich Theodore , Cloninger C. Robert , Nurnberger John I. , Kowalczuk Maria , Wu Bo , Li T.‐K. , Conneally P. M. , Tischfield Jay A. , Wu William , Shears Shantia , Crowe Raymond , Hesselbrock Victor , Schuckit Marc , Porjesz Bernice , Begleiter Henri
Published: May 2006

The possible association of the DRD2 locus, and in particular the 7aql‐A1 allele, with alcoholism remains controversial, in part because of differences in allele frequencies among populations. To avoid problems associated with differences in allele frequencies in different populations, we tested whether the DRD2 locus is associated with alcohol dependence in a large family‐based sample. Neither the transmission/disequilibrium test nor the Affected Family‐Based Controls test provide any evidence of linkage or association between the DRD2 locus and alcohol dependence.
Relationship of Binge Drinking to Alcohol Dependence, Other Psychiatric Disorders, and Behavioral Problems in an American Indian Tribe
Authors: Robin Robert W. , Long Jeffrey C. , Rasmussen Jolene K. , Albaugh Bernard , Goldman David
Published: May 2006

The hypothesis that binge drinking is a benign behavior not associated with alcohol dependence, other psychiatric disorders, or problem areas, in American Indians, was tested in a sample of 582 adult Southwestern American Indian males and females in large multigenerational pedigrees. All information was obtained from semistructured psychiatric interviews that were independently blind‐rated for DSM‐III‐R diagnoses. Three main outcome measures were used: the relationship between binge drinking and (1) alcohol dependence and other psychiatric disorders, (2) substance abuse treatment, and (3) four behavioral problem categories‐violence/lawlessness, physical, social, and work. Binge drinking and alcohol dependence were strongly associated. Most binge drinkers were diagnosed as alcohol dependent. However, when controlling for alcohol dependence and other covariates, binge drinking was independently associated with an increase in odds for positive diagnoses for multiple psychiatric disorders, and for social, work, physical, and violence/lawlessness behavioral problems. In sum, binge drinking was found to be a common and severe problem with deleterious consequences in multiple domains of functioning. Assessment instruments should be designed to elicit information on binge patterns of drinking and strategies devised to provide appropriate treatment.
The Alcoholics Anonymous Affiliation Scale: Development, Reliability, and Norms for Diverse Treated and Untreated Populations
Authors: Humphreys Keith , Kaskutas Lee Ann , Weisner Constance
Published: May 2006

Affiliation with Alcoholics Anonymous (AA) is an important variable to measure in many clinical and research activities. This paper reports on the development of an AA affiliation scale, and demonstrates its utility in a sample of 927 alcohol treatment seekers and 674 untreated problem drinkers. The scale is short (9 items), covers a range of AA experiences, and is internally consistent across diverse demographic groups, multiple health services settings, and treated and untreated populations. The validity of the scale is supported by the findings that treatment seekers report significantly higher AA affiliation than do untreated problem drinkers, and inpatients report higher affiliation than outpatients. Potential clinical and research applications of the scale are proposed.
A Critical Evaluation of Several Alcohol Screening Instruments Using the CIDI‐SAM as a Criterion Measure
Authors: Clements Richard
Published: May 2006

Four alcohol screening instruments (the AUDIT, CAGE, MAST, and Svanum's scale) were administered to a sample of 306 undergraduate students at a Midwestern university and were compared with regard to several test characteristics, using the alcohol section of the CIDI‐SAM (DSM‐IV version) as the criterion measure. The performance of these instruments was evaluated using two subsets of subjects: (1) students who currently met diagnostic criteria for alcohol dependence (n= 35); and (2) students who met diagnostic criteria for alcohol dependence in the past and/or at present (i.e., lifetime diagnosis; n= 50). The AUDIT performed significantly better than the other three instruments in identifying students who were currently alcohol dependent, providing a moderate degree of clinical utility with this group. The four instruments did not differ significantly in their ability to identify students with a lifetime diagnosis; each measure provided only a modest degree of clinical utility with this group.
Does Carbohydrate‐Deficient Transferrin Predict the Severity of Alcohol Withdrawal Syndrome?
Authors: Wetterling T. , Kanitz R.‐D. , Renner F. , Fischer D.
Published: May 2006

Alcohol withdrawal often causes severe complications. However, many addicts deny any abuse. Thus, the diagnosis of alcohol abuse frequently becomes difficult. Laboratory parameters are often used to support the diagnosis of alcohol abuse. Furthermore, laboratory parameters should facilitate the prediction of the severity of alcohol withdrawal syndrome (AWS). The most promising laboratory parameter indicating a recent elevated alcohol consumption is carbohydrate‐deficient transferrin (CDT). The aim of this study was to examine whether the measurement of CDT at admission can indicate a higher risk for the development of a complicated AWS. The severity of AWS was assessed by the AWS scale, consisting of two subscales for somatic and mental symptoms. CDT was measured by different methods (radioimmunoassay and HPLC). The radioimmunoassay for CDT (CDTect) yielded the best prediction. Our results showed a weak correlation between CDTect and the severity of AWS. However, there were great gender differences. In men, CDTect had the highest positive predictive value for a severe AWS (86.7%), whereas in women mean corpuscular volume was the best predictor (77.8%). However, the sensitivity of CDTect in men (25.5%), as well as mean corpuscular volume in females (29.2%), was too low for a screening test in a general hospital.
A Family‐Based Analysis of Whether the Functional Promoter Alleles of the Serotonin Transporter Gene HTT Affect the Risk for Alcohol Dependence
Authors: Edenberg Howard J. , Reynolds Jennifer , Koller Daniel L , Begleiter Henri , Bucholz Kathleen K. , Conneally P. Michael , Crowe Raymond , Goate Alison , Hesselbrock Victor , Li T.‐K. , Numberger John I. , Porjesz Bernice , Reich Theodore , Rice John P. , Schuckit Marc , Tischfield Jay A. , Foroud Tatiana
Published: May 2006

A population association between a regulatory variation in the promoter of the serotonin transporter gene (HTT) and severe alcohol dependence was recently reported. We analyzed this potential association in a large number of systematically ascertained families in the United States; these families had at least three first‐degree relatives who were alcohol‐dependent. Analyses focused on individuals defined as alcohol‐dependent by criteria from ICD‐10 and on subsets of these individuals reporting withdrawal‐related symptoms. Application of the transmission disequilibrium test did not provide support for either linkage or association between this functional polymorphism and alcohol dependence; there was no significant bias in the transmission of either allele to the alcohol‐dependent offspring. We also report that African Americans differ from Caucasians in allele frequencies for this polymorphism.
Inhibition of Intracolonic Acetaldehyde Production and Alcoholic Fermentation in Rats by Ciprofloxacin
Authors: Visapää J.‐P. , Jokelainen K. , Nosova T. , Salaspuro M.
Published: May 2006

Heavy drinking is associated with many gastrointestinal symptoms and diseases, such as rapid intestinal transit time, diarrhea, colon polyps, and colorectal cancer. Acetaldehyde produced from ethanol by intestinal microbes has recently been suggested to be one of the pathogenetic factors related to alcohol‐associated gastrointestinal morbidity. Furthermore, acetaldehyde is absorbed from the colon into portal blood and may thus contribute to the development of alcoholic liver injury. The present study was aimed to investigate the significance of gut aerobic flora in intracolonic acetaldehyde formation. For this study, 58 male Wistar rats (aged 9 to 11 weeks) were used. Half of the rats received ciprofloxacin for four consecutive days. Control rats (n= 29) received standard chow. On the fifth day of treatment, 1.5 g/kg body weight of ethanol was administered intraperitoneally to 19 rats receiving ciprofloxacin and 19 control rats. Ten ciprofloxacin‐treated and 10 control rats received equal volumes of physiological saline intraperitoneally. Two hours after the injection of ethanol or saline, the samples of colonic contents and blood were obtained. Acetaldehyde and ethanol levels of the samples were determined by headspace gas chromatography. The intracolonic acetaldehyde level 2 hr after ethanol administration was 483 ± 169 μM (maximum: 2.7 mM). High intracolonic acetaldehyde after ethanol injection was significantly reduced by ciprofloxacin treatment. After ciprofloxacin, intracolonic acetaldehyde levels before and after the injection of ethanol were 25 ± 4.8 and 23 ± 15 μM, respectively. Ciprofloxacin treatment resulted also in significantly higher blood (p < 0.005) and intracolonic (p < 0.0001) ethanol levels than in the control animals. Furthermore, ciprofloxacin treatment totally abolished the formation of endogenous ethanol in the large intestine. This study demonstrates that alcoholic fermentation and intracolonic acetaldehyde production can be blocked by diminishing the amount of intracolonic aerobic bacteria with ciprofloxacin. Our findings indicate that the bacteriocolonic pathway for ethanol oxidation is mediated almost exclusively by gut aerobic microbes, and this knowledge may provide new insights into the studies on the pathogenesis of alcohol‐related gastrointestinal symptoms and diseases.
VTA Dopamine Neuron Activity Distinguishes Alcohol‐Preferring (P) Rats from Wistar Rats
Authors: Morzorati Sandra L.
Published: May 2006

The mesolimbic dopamine (DA) system is innately deficient in rats selectively bred for high alcohol drinking behavior compared with rats selectively bred for low alcohol drinking and unselected rats. In alcohol‐preferring (P) rats, compared with alcohol‐nonpreferring (NP) rats, this is evidenced by fewer DA neurons in the ventral teg‐mental area (VTA) projecting to the nucleus accumbens (ACB). Yet, despite this deficiency, DA release in the ACB is similar in P, NP, and Wistar rats. DA release is regulated by DA neuronal activity, and DA neurons fire tonically as well as in bursts. Burst firing has been shown to substantially enhance DA release compared with tonic firing. The present study was designed to test the hypothesis that the remaining VTA DA neurons in P rats have faster firing frequencies and/or burst fire more frequently than VTA DA neurons in Wistar rats. The spontaneous activity of VTA DA neurons was recorded in un‐anesthetized alcohol‐naive P and Wistar rats. A conventional burst analysis on 500 consecutive action potentials revealed that P rats had a significantly (p < 0.05) greater percentage of action potentials in bursts when compared with Wistar rats (P 50.9%, Wistar: 34.4%). Firing frequency and other burst parameters (burst interspike interval, burst length, interburst interval, and the number of action potentials per burst) did not distinguish the two groups of rats. The increased burst activity in P rats may represent a compensatory mechanism to maintain adequate basal levels of DA despite the deficiency in the mesolimbic DA system.
Prenatal Ethanol Exposure Induces a Sexually Dimorphic Effect on Daily Water Consumption in Prepubertal and Adult Rats
Authors: McGivern Robert F. , Ervin M. Gore , McGeary John , Somes Christine , Handa Robert J.
Published: May 2006

Previous studies have shown that female rats consume significantly more water than males on a weight basis. Because exposure to alcohol during the last week of gestation is associated with incomplete behavioral defeminization in male rats, we examined daily water intake in fetal alcohol‐exposed (FAE) males and females. Time‐pregnant multiparous Sprague‐Dawley dams were administered an ethanol liquid diet containing 35% ethanol‐derived calories from day 14 through parturition. At 80 days of age, daily water consumption of FAE males and female litter representatives was measured for 7 days. FAE males, but not females, consumed significantly more water than their pair‐fed counterparts. Subsequent experiments determined that the increased water consumption in FAE males is present prepubertally, persists into mature adulthood, and is not influenced by prenatal or postnatal castration. Chronic estrogen treatment induced large increases in water consumption, but consumption of FAE males remained elevated over elevated pair‐fed male consumption, indicating that pituitary sensitivity to estrogen was not increased in FAE males. Morphometric studies of hypothalamic nuclei containing vasopressin cells revealed no long‐term effects of prenatal ethanol exposure on the volume of the supraoptic nucleus or paraventricular nucleus in males, nor was an effect observed in the ventromedial nucleus measured as a control. In FAE females, the volume of the paraventricular nucleus was significantly smaller than chow‐fed controls. Whereas baseline plasma and pituitary arginine vasopressin (AVP) levels of FAE animals and pair‐fed controls were not significantly different, AVP content was significantly reduced in the septal/bed nucleus region in brains of FAE animals of both sexes. Overall, these data indicate that prenatal ethanol exposure increases male water consumption in the absence of alterations in basal plasma AVP.
Work Control, Work Demands, and Work Social Support in Relation to Alcoholism Among Young Men
Authors: Hemmingsson Tomas , Lundberg Ingvar
Published: May 2006

Objectives: The aim of the study was to estimate the impact of psychosocial work‐environment factors, such as low work control, on alcoholism among young men. Methods: Data on circumstances during childhood and adolescence, such as on risk use of alcohol, were collected for 49,323 young men, born 1949 to 1951 at time of enlistment for compulsory military training in 1969/1970. On the basis of census data on occupation in 1975, all individuals were classified into groups with regard to psychosocial work‐environment factors in accordance with a job‐exposure matrix. Follow‐up for alcoholism diagnoses from inpatient care registers (1976 to 1983) was undertaken for each of the groups. A number of potential confounding factors were taken into account. Results: Low work control and also low job demands and low workplace social support were found to be related to later alcoholism. On separate analysis, the pattern among blue‐collar workers was found to be similar to that of the entire population. When the analyses were extended to include indicators of risk use of alcohol and other relevant background factors, the relative risks decreased, but were still significantly high in the cases of low work control and low work social support. A combination of low demands and low control, what might be called a “passive” work environment, was related to an increased relative risk of psychiatric alcoholism diagnosis after controlling for relevant background factors. Conclusions: Low work control, in particular in combination with low work demands, and low work social support are related to later alcoholism even after controlling for previously known risk factors (including risk use of alcohol). The results suggest that young men may respond to an undemanding occupational environment by increasing their alcohol consumption.
Alcohol Consumption and Breast Cancer Stage at Diagnosis
Authors: Vaeth Patrice A. C. , Satariano William A.
Published: May 2006

The stage at which breast cancer is diagnosed is an important determinant of prognosis. In contrast to the many investigations of the relationship between alcohol consumption and the risk of developing breast cancer, few have examined how alcohol consumption may affect the stage of this cancer at diagnosis. This article examines the relationship between alcohol intake and breast cancer stage and assesses consumption in relation to the volume of drinks consumed per week and the patterns of consumption 1 year prior to the breast cancer diagnosis. A total of 1191 women, aged 40 to 84 years, with newly diagnosed breast cancer were identified through the population‐based Metropolitan Detroit Cancer Surveillance System, a participant of the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute. Of these, 1011 (85%) were interviewed 2 to 4 months following diagnosis. The analyses for this article were limited to 920 cases with local and regional stage disease. The bivariate analysis showed that frequent drinkers were more likely than abstainers or infrequent drinkers to present with regional disease. Logistic regression showed that frequent drinkers were 1.45 times more likely than infrequent drinkers to be diagnosed with later stage breast cancer (95% CI: 1.01–2.10; p= 05). The association between alcohol consumption and disease stage may be due to the relationship between heavy consumption and other unhealthy behaviors. In addition, women who drink more frequently may have less awareness of and access to cancer screening services. Heavy exposure to alcohol may also contribute to accelerated tumor growth once breast cancer is present.
Neurocognitive Deficits in Alcoholics and Social Drinkers: A Continuum?
Authors: Parsons Oscar A.
Published: May 2006

Our research program has investigated neurocognitive deficits in sober alcoholics for several decades. We have shown that both male and female adult alcoholics – compared with peer nonalcoholic controls – have deficits on tests of learning, memory, abstracting, problem‐solving, perceptual analysis and synthesis, speed of information processing, and efficiency. The deficits are equivalent to those found in patients with known brain dysfunction of a mild to moderate nature. Attempts to identify factors other than alcoholism to account for these differences have been unsuccessful. The deficits appear to remit slowly over 4 to 5 years. Relapse of recovering alcoholics is predicted by behavioral (e.g., depressive symptoms and neurocognitive performance) and biological measures (e.g., event‐related potentials) obtained at the end of treatment. Results of recent studies support the hypothesis of a continuum of neurocognitive deficits ranging from the severe deficits found in Korsakoff patients to moderate deficits found in alcoholics and moderate to mild deficits in heavy social drinkers (more than 21 drinks/week). Individual differences in the presence and magnitude of neurocognitive deficits in social drinkers and alcoholics are hypothesized to be due, in part, to individual differences in vulnerability of the brain to alcohol or its metabolites' toxic effects.
Chronic Ethanol Treatment Leads to Increased Ornithine Decarboxylase Activity: Implications for a Role of Polyamines in Ethanol Dependence and Withdrawal
Authors: Davidson Mark , Wilce Peter
Published: May 2006

Recent research has focused on the N‐methyl‐D‐aspartate receptor system as a major site of ethanol action in the brain and specifically on compensatory changes in the expression of the polyamine‐sensitive NR2B subunit. Therefore, we examined the effects of chronic ethanol treatment on polyamine homeostasis in the rat brain. Wistar rats were made dependent by ethanol vapor inhalation. This caused a rise in hippocampal omithine decarboxylase (ODC) activity that was correlated with the appearance of physiological dependence. ODC activity returned to control levels within 3 days of ethanol withdrawal. Enzyme activity also increased in the cerebral cortex, striatum, and cerebellum of the ethanol‐dependent rats. The concentration of the polyamines (putrescine, spermidine, and spermine) in the hippocampus was increased in ethanol‐dependent rats. Injection of the ODC inhibitor, α‐difluoromethylomithine (500 mg/kg) at the onset of withdrawal resulted in a significant reduction in the severity of withdrawal behaviors. The level of ODC activity and the severity of withdrawal behaviors were positively correlated. Perturbed polyamine homeostasis may represent an important molecular component in the initiation of ethanol withdrawal behaviors in the ethanol‐dependent rat.
Early Events in the Development of Neuronal Polarity In Vitro Are Altered by Ethanol
Authors: Clamp Penelope A. , Lindsley Tara A.
Published: May 2006

Among the neuropathological effects of prenatal exposure to ethanol is the disruption of neuromorphogenesis. The effects of ethanol on early events in the development of axons and dendrites were studied using cultured embryonic rat hippocampal neurons, which develop in vitro in a stereotypical sequence of events that mimics their development in vivo. During the first 24 hr in culture, hippocampal neurons attach to the substrate and develop into one of three stages identified by phase‐contrast microscopy: (i) neurons having lamellipodia and no processes (stage 1); (ii) neurons developing minor processes (<40 μm) that subsequently become the cell's axon or dendrites (stage 2); or (iii) polarized neurons with at least one axon (process with length ≥40 μm) (stage 3). Exposure to ethanol (300 mg/dl or 800 mg/dl) in the culture medium resulted in an increase in both the number of minor processes per neuron and the number of stage 3 neurons having more than the typical single axon. In addition, ethanol exposure significantly altered the proportion of neurons in the three early stages of development at 18 to 24 hr in vitro, without affecting overall neuron survival. With ethanol, there was a smaller proportion of neurons in the first stage of development, and a greater proportion of polarized stage 3 neurons. These findings suggest that ethanol alters the normal establishment of neuronal polarity, disrupting mechanisms that ensure the formation of the appropriate number of processes and that regulate the timing of process outgrowth.
Amplitude of Visual P3 Event‐Related Potential as a Phenotypic Marker for a Predisposition to Alcoholism: Preliminary Results from the COGA Project
Authors: Porjesz B. , Begleiter H. , Reich T. , Van Eerdewegh P. , Edenberg H. J. , Foroud T. , Goate A. , Litke A. , Chorlian D. B. , Stirnus A. , Rice J. , Blangero J. , Almasy L. , Sorbell J. , Bauer L. O. , Kuperman S. , O'Connor S. J. , Rohrbaugh J.
Published: May 2006

Recent data collected at six identical electrophysiological laboratories from the large national multisite Collaborative Study on the Genetics of Alcoholism provide evidence for considering the P3 amplitude of the event‐related potential as a phenotypic marker for the risk of alcoholism. The distribution of P3 amplitude to target stimuli at the Pz electrode in individuals 16 years of age and over from 163 randomly ascertained control families (n= 687) was compared with those from 219 densely affected alcoholic families (n= 1276) in which three directly interviewed first‐degree relatives met both DSM‐III‐R and Feighner criteria at the definite level for alcohol dependence (stage II). The control sample did not exclude individuals with psychiatric illness or alcoholism to obtain incidence rates of psychiatric disorders similar to those of the general population. P3 amplitude data from control families was converted to Z‐scores, and a P3 amplitude beyond 2 SD's below the mean was considered an “abnormal trait.” When age‐ and sex‐matched distributions of P3 amplitude were compared, members of densely affected stage II families were more likely to manifest low P3 amplitudes (2 SD below the mean) than members of control families, comparing affected and unaffected offspring, and all individuals; all comparisons of these distributions between groups were significant (p < 0.00001). P3 amplitude means were also significantly lower in stage II family members, compared with control family members for all comparisons, namely probands, affected and unaffected individuals (p < 0.000l), and offspring (p < 0.01). Furthermore, affected individuals from stage II families, but not control families, had significantly lower P3 amplitudes than unaffected individuals (p 0.001). Affected males from stage II families had significantly lower P3 amplitudes than affected females (p < 0.001). Recent linkage analyses indicate that visual P3 amplitude provides a biological phenotypic marker that has genetic underpinnings.
Mismatch Negativity in Young Children of Alcoholics from High‐Density Families
Authors: Holguín Socorro Rodríguez , Corral Montserrat , Cadaveira Fernando
Published: May 2006

The mismatch negativity (MMN) component of event‐related potentials was recorded from a group of young children of alcoholics (n= 19, 8 females) with a high‐density family history of alcoholism and from a control group (n= 23,12 females), between 8 and 15 years of age. A dichotic listening task was used, and subjects had to pay attention to an oddball paradigm in one ear and ignore the stimuli in the other ear. The event‐related potentials elicited by the standard unattended tones were subtracted from those elicited by the infrequent deviant unattended tones, and the MMN was measured at 10 frontal and central electrodes. No group differences were observed in peak latency, peak amplitude, and mean amplitude of the MMN. These results indicated that preattentive mechanisms of mismatch detection were not impaired in young subjects at high risk for alcoholism. Results are discussed in relation to differences in electro‐physiological indexes of automatic versus controlled information processing and in relation to the characteristics of the sample.
Short‐Term Effects of Maternal Alcohol Consumption on Lactational Performance
Authors: Mennella Julie A.
Published: May 2006

Previous research demonstrated that breast‐feeding infants consumed significantly less milk during the immediate hours after their mothers consumed an acute dose of alcohol when compared with a nonalcoholic beverage. The present study tested the hypothesis that maternal alcohol consumption decreases the amount of milk available to the infant and alters milk composition in the short term. To this aim, 22 lactating women were tested on 2 days separated by 1 week; the women reported that they drank very little during pregnancy, but significantly increased alcohol intake during lactation. Each woman drank a 0.3 g/kg dose of alcohol in orange juice on one testing day and orange juice alone on the other; the order was counterbalanced. Immediately before drinking the beverage (baseline) and 2 hr after (postconsumption), women expressed their milk by using an electric breast pump until no milk had been secreted from either breast for 5 min. Although there was no difference in the energy content of the milk, maternal alcohol consumption slightly, but significantly, reduced the amount of milk produced by the lactating mother. These findings underscore the importance of determining whether and when infants compensate for the reductions in intake experienced at the breast following maternal alcohol consumption and how such changes impact on mother‐infant interaction.
Performance of Screening Instruments for Identifying Alcohol Dependence in the General Population, Compared with Clinical Populations
Authors: Cherpitel Cheryl J.
Published: May 2006

Screening instruments for problem drinking have been developed in clinical populations, and little is known of their performance in the general population. Sensitivity and specificity of the CAGE and the TWEAK for ICD‐10 and/or DSM‐IV criteria for alcohol dependence are compared among those sampled from the southern region in the 1995 National Alcohol Survey (n= 776). and from emergency room (ER) (n = 1327) and primary care clinic (n= 767) samples in Jackson, MS. Sensitivity of the CAGE was higher in both the ER (85%) and primary care (82%) samples than in the general population (75%), although differences were not significant, and this held for males and females alike. Sensitivity of the TWEAK was lower in the general population sample (83%) than in the ER sample (89%), but higher than in the primary care sample (75%). In the general population, sensitivity of both screeners was better (although not significantly so) among those making an ER or primary care visit during the last year than among those not doing so, with the largest difference found for the CAGE (85% vs. 65%, respectively). In a merged sample of the three sites, the interaction of site by screening instrument was not a significant predictor of alcohol dependence for either the CAGE or TWEAK. Data suggest that screening instruments may not perform as well in the general population as in some clinical populations, with more variation apparent across groups for some screeners than for others. Although further analysis is necessary to explore this issue further, attention should be given to selection of the best instrument for use in a given population.
Impairment of Semantic and Figural Memory by Acute Ethanol: Age‐Dependent Effects
Authors: Acheson Shawn K. , Stein Roy M. , Swartzwelder H. S.
Published: May 2006

Alcohol drinking is prevalent among young adults in the US. Moreover, heavy drinking is acknowledged by a substantial percentage of young adults in both college and military subpopulations, despite the known cognitive demands associated with these endeavors and the cognitive impairments associated with alcohol usage. We assessed the acute effects of ethanol (0.6 g/kg) on the acquisition of both semantic and figural memory in a sample of young adults from 21 to 29 years of age using a repeated‐measures, placebo‐controlled experimental design. Ethanol significantly impaired memory acquisition in both domains. In addition, the effect of ethanol on three of the four memory measures assessed was dependent on the age of the subjects. Subjects in a young subgroup (21 to 24 years of age) were significantly more impaired in memory measures than those in the subgroup that was 25 to 29 years of age. These results indicate a divergence of the potency of ethanol against memory acquisition across a narrow age range in early adulthood. Whereas these data are preliminary, and should be generalized cautiously, they are also consistent with a growing literature using animal models that indicates that acute ethanol is a more potent antagonist of memory and memory‐related hippocampal activity in adolescent animals compared with adults.
Long‐Term Change in Underage Drinking and Impaired Driving After the Establishment of Drinking Age Laws in New York State
Authors: Yu Jiang , Shacket Robin W.
Published: May 2006

This study depicts the long‐term change in youths' alcohol use and impaired driving behaviors associated with the establishment of the drinking age laws. Five telephone surveys were conducted with youths aged 16 to 24 in 10 sampled New York State counties in 1982, 1983, 1985, 1986, and 1996. Analysis of the self‐reported data showed that, 10 years after the enactment of the 21 drinking age law, alcohol use among la‐, 19‐, and 20‐year‐olds decreased by up to 58%. Alcohol purchase rates of 19‐ and 20‐year‐olds were reduced by ∼70% from 1985 to 1996. Although impaired driving rates declined over the survey years for each age group, ∼25% of all underage respondents in 1996 reported that they had ridden in a vehicle with an impaired driver. Findings from this research indicate that alcohol purchase, alcohol use, and impaired driving have declined among the targeted youth groups as a result of the 21 drinking age law. However, continued efforts need to focus on both underage drinking and impaired driving/riding with impaired drivers, because they remain serious public health risks among the youth population.
Screening Trauma Patients for Alcoholism According to NLAAA Guidelines with Alcohol Use Disorders Identification Test Questions
Authors: Soderstrom Carl A. , Dischinger Patricia C. , Kerns Timothy J. , Kufera Joseph A. , McDuff David R. , Gorelick David A. , Smith Gordon S.
Published: May 2006

Drinking pattern criteria (drinking frequency and number of drinks per occasion) issued by the National Institute on Alcohol and Abuse and Alcoholism (NIAAA) to screen primary practice patients for alcohol problems were evaluated in 1216 injured patients treated in a regional trauma center. Vehicular crash victims predominated (50.2%, of whom 64.5% were drivers), followed by victims of violence (31.2%) and nonviolent‐injury victims (18.5%). Alcohol Use Disorders Identification Test (AUDIT) questions #1 (drinking frequency) and #2 (drinks/day) were used to assess the patients for current alcohol dependence (CAD). AUDIT responses roughly approximating NIAAA guidelines (high threshold: drinks ≥ 4 times/week, ≥ 5 drinks/day) and those indicating less drinking (low threshold: drinks ≥ 2‐3 times/week, ≥3 drinks/day) were chosen. Comparisons were made relative to sensitivity and specificity of responses in detecting CAD. When low threshold responses were used for either question, sensitivity to detect CAD increased overall (#1 from 0.53 to 0.80, #2 from 0.62 to 0.88) as well as among the subgroups of patients, whereas specificity remained high or at acceptable levels overall (#1 from 0.95 to 0.82, #2 from 0.92 to 0.71) and among the subgroups of patients. Study findings suggest that, among injured drivers and other groups of trauma center patients, lesser amounts of drinking should be used as screening criteria for CAD than are used for the general population.
Behavioral Impairment Under Alcohol: Cognitive and Pharmacokinetic Factors
Authors: Fillmore Mark T. , Vogel‐Sprott M.
Published: May 2006

This study tested the hypothesis that the intensity of behavioral impairment under alcohol is related to social drinkers' expectancies about impairment and their rates of rise in blood alcohol concentration (BAC). After subjects (n= 30) were trained on a psychomotor task, they rated the impairment they expected from alcohol and then performed the task under alcohol (0.56 g/kg) or a placebo. Alcohol impaired performance, compared with placebo. Drinkers' expectations about impairment and their rates of rise in BAC were independent, and each factor predicted a significant portion of the variance in alcohol impairment among drinkers. More intense impairment under alcohol was associated with expectations of greater impairment and with swifter rates of rise in BAC. BACs obtained by drinkers during task performance were not related to the intensity of impairment they displayed. The study shows that a pharmacological and nonpharmacological variable can each affect a drinker's behavioral impairment under alcohol, and this finding contributes to our understanding of conditions where BAC per se may be an unreliable indicator of impairment.
Sensitivity to Ethanol Across Development in Rats: Comparison to [3H]Zolpidem Binding
Authors: Moy Sheryl S. , Duncan Gary E. , Knapp Darin J. , Breese George R.
Published: May 2006

Previous research has suggested that rats tested at 28 to 30 days of age show a marked subsensitivity to the sedative effects of ethanol. In the present study, rats of different ages were tested for aerial righting following acute ethanol (3 g/kg) treatment. These results were compared with the effects of the atypical benzodiazepine zolpidem (3 and 5 mg/kg) and pentobarbital (10 and 15 mg/kg). Animals tested at 25,28, or 35 days of age were significantly less impaired by ethanol than preweanling rats (age 20 days) or older rats (age 65 to 75 days), whereas animals tested at 25 or 28 days of age were less impaired by the higher dose of zolpidem. With pentobarbital, the most distinct age‐related trend was greater impairment in 20‐day‐old rats. Because ethanol may be active at the same type I GABAA receptor site selectively labeled by [3H]zolpidem, levels of [3H]zolpi‐dem binding were determined for rats of different ages. Although some brain regions showed progressive increases in binding of [3H]zolpidem across development, other regions demonstrated increased binding from day 12 or 17 to day, then a plateau of binding levels across days 25, and 28, with further increases occurring by day 36 or day 60. This pattern was observed in the cingulate cortex, medial septal nucleus, globus pallidus, inferior colliculus, red nucleus, and cerebellum. Overall, the results indicate that the period of subsensitivity to the sedative effects of ethanol is coincident with a change in the developmental pattern of GABAA receptor sites targeted by [3H]zolpidem.
A Comparison of Lipopolysaccharide‐Induced Hepatitis in Ethanol‐Fed Wistar and Lewis Rats
Authors: Pennington Helen L. , Wilce Peter A. , Worrall Simon
Published: May 2006

Elevated concentrations of plasma proinflammatory cytokines have been detected in patients with alcoholic hepatitis (AH) and in a model of lipopolysaccharide‐induced hepatitis in ethanol‐fed Wistar rats. These cytokines have been implicated in the pathogenesis of the liver damage. Considering the likely involvement of the immune system in AH, and the frequent use of Lewis rats in autoimmune disease models, Lewis rats were examined in the model to determine whether they would more closely mimic the immune status of a chronic alcoholic and be a preferable strain for use in future experiments. Lipopolysaccharide‐induced hepatic tumor necrosis factor‐α, interleukin‐1α, interleukin‐1β, and interleukin‐6 mRNA expression was examined in both rat strains. The overall pattern of histological (panlobular piecemeal necrosis) and biochemical liver damage (plasma ALT levels), and cytokine expression was similar in both strains. Thus, it would appear that, despite the known susceptibility of Lewis rats to autoimmune phenomena, they do not respond to the experimental regime significantly better than Wistar rats. This study confirms that unknown mediators are contributing to the liver damage seen in this model and possibly in AH.
Ursodeoxycholate Alleviates Alcoholic Fatty Liver Damage in Rats
Authors: Oliva L. , Beaugé F. , Choquarl D. , Montet A. M. , Guitaoui M. , Montet J. C.
Published: May 2006

The hydrophilic bile salt ursodeoxycholate (UDC) improves cholesta‐sis in several liver diseases and is in vitro an efficient membrane stabilizer. However, its action on chronic ethanol‐induced liver damage is not established. We thus sought to determine the effect of UDC on chronic ethanol‐induced steatosis and on liver plasma membrane fluidity in rats. Male rats were pair‐fed liquid diets containing 36% of calories as ethanol (alcohol diet) or an isocaloric maltose‐dextrin mixture (control diet). Four groups of 10 animals received, respectively, during 30 days: the control diet, the control diet + UDC (90 mg/kg/day), the alcohol diet, and the alcohol diet + UDC. Bile was collected for assessment of bile flow, biliary lipids, and individual bile salts. Liver lipid contents and lipid peroxidation were determined. Plasma membrane fluidity was assessed by fluorescence polarization of various probes. Alcohol treatment caused a 4‐fold increase in liver triacylglycerol and cholesterol ester levels. UDC supplementation significantly reduced these increases by 50% and 40%, respectively. UDC intake was associated with a marked decrease in alcohol‐induced lipid peroxidation. Bile flow, bile salt, and phosphor‐lipid secretion were slightly increased by alcohol intake. The addition of UDC‐enriched bile with tauroursodeoxycholate (38%) without significantly affecting the biliary parameters. Lastly, UDC treatment almost totally prevented the 20% increase in liver plasma membrane fluidity due to chronic alcohol intake. This study shows that UDC intake, concomitant with alcohol diet, exerts a clear‐cut membrane protective effect that might alleviate ethanol‐induced lipid disorders.
Intragastric Intubation: Important Aspects of the Model for Administration of Ethanol to Rat Pups During the Postnatal Period
Authors: Light Kim Edward , Kane Cynthia J. M. , Pierce Dwight R. , Jenkins Donna , Ge Yun , Brown Ginger , Yang Haijuan , Nyamweya Nasser
Published: May 2006

One technique for the controlled delivery of ethanol to neonatal rat pups is intragastric intubation. Often, the vehicle used for delivery of ethanol is composed of a nutrient mixture to compensate for decreased suckling or other possible nutritional compromise. This study analyzed the selection of nutrient vehicle, the combination of experimental treatment groups within a litter, and the overall litter size on the growth rate of ethanol‐intubated and intubated‐control pups, compared with mother‐raised control pups. Sprague‐Dawley rat pups were raised in litters of 8 or 10, and administered ethanol by intragastric intubation with 20% (v/v) Sustacalm or 80% (v/v) Intralipid‐II® nutrient vehicle. Pups were treated between postnatal days 2 and 10, and body weight was analyzed on day 10. Pups were assigned to a treatment group as either intubated ethanol, intubated control, or nonintubated mother‐raised controls. Experimental comparison by statistical analyses was performed to identity the optimal treatment design (mixed treatment groups in a single litter or a single treatment group per litter), the optimal vehicle (Sustacal® or Intralipid‐II®), and the optimal number of pups per litter (8 vs. 10). The analyses demonstrate that the mixing of intubated control, intubated ethanol, and nonintubated mother‐raised control treatment groups within a single litter introduced an uncontrolled variable that confounded measurement of ethanol‐specific alterations. The sensitivity of treatment groups to inclusion in mixed litters was dependent on the nutrient vehicle and thus nutritional adequacy. Our results suggest that an optimal design was achieved with eight pups per litter. Furthermore, ethanol intubated and intubated control pups grow at a rate identical to parallel litters of eight mother‐raised control pups when Intralipid‐II® is used as nutrient vehicle, and a single treatment group is present in a litter. Optimization of these experimental parameters has provided an excellent neonatal rat model for analysis of specific ethanol effects on brain development during the third trimester.