bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic Determinants of Alcohol Addiction and Metabolism: A Survey in Italy
Authors: Pastorelli Roberta , Bardazzi Gabriele , Saieva Calogero , Cerri Annalisa , Gestri Donella , Allamani Allaman , Airoldi Luisa , Palli Domenico 
Published: April 2006

Background: Although multiple genes are involved in alcoholism and can contribute differently to the risk of dependence and liver damage, no studies have investigated susceptibility to addiction in combination with susceptibility to liver damage due to differences in ethanol metabolism.Methods: We evaluated the role of three polymorphic genes related to alcohol metabolism (CYP2E1) and, possibly, dependence (DRD2 and SLC6A4 promoter) in a series of 60 alcoholics admitted to a specialized referral center in Florence, Italy. Eighteen had a diagnosis of liver cirrhosis. A control series of 64 blood donors were identified at the same hospital. Genotyping was done by polymerase chain reaction‐restriction fragment length polymorphism methods.Results: No difference was found in the frequency of the CYP2E 1 Rsa I c2 allele (2.5% among alcoholics and 4.7% among controls) and the Dra I C allele (6.7% and 10.1%). Similarly, no difference was found in the frequency of the DRD2 A1 allele (15.8% and 13.3%) and the B1 allele (10.8% and 8.6%). The proportion of controls with a combined B1 genotype (B1/B1 or B1/B2) was significantly associated with smoking (p= 0.03). The distribution of the S and L allele of the SLC6A4 gene was similar in the two groups, with 15% and 14%, respectively, homozygous S/S carriers. A significant association, however, emerged in the group of alcoholics, with a five times higher risk for S/S carriers of developing cirrhosis (p < 0.05). This association with liver persisted even after exclusion of the subgrouped of 10 hepatitis C virus positive alcoholics.Conclusions: Overall, our results provided no evidence of an increased susceptibility to develop alcoholism that was associated with the three genotypes investigated, either alone or in combination. An increased risk of developing liver cirrhosis for S/S homozygous carriers among alcohol‐dependent patients was observed for the first time.
Coronary Artery Disease Modifies Left Ventricular Remodelling due to Heavy Alcohol Consumption
Authors: Kajander Olli A. , Kupari Markku , Laippala Pekka , Penttilä Antti , Karhunen Pekka J. 
Published: April 2006

Background: Coronary artery disease (CAD) and e‐cessive alcohol use can both damage the myocardium. Their combined effect on the heart muscle has not been characterized. We set out to assess whether the presence of CAD modifies the effects of chronic alcohol consumption on the left ventricular (LV) structure in middle‐aged men.Methods: A postmortem e‐amination was performed on 700 Finnish men (age range, 33–70 years) who e‐perienced a sudden, nonhospital death. A coronary arteriography and measurement of the LV wall thickness, cavity area, and ratio by planimetry of transversal ventricular slices were done at the autopsy. The men were grouped by the most severe coronary artery diameter stenosis (<30%, 30–60%, >60%) and by daily alcohol dose (<12 g, 12–72 g, 72–180 g, >180 g) estimated by a structured interview of their lifetime partner.Results: Analysis by ANCOVA, adjusted for age, body size, smoking, hypertension, and diabetes, showed a statistically significant interaction between the effects of coronary artery stenosis and daily alcohol dose on the LV cavity area (p= 0.037) and on the LV wall thickness/cavity area ratio (p= 0.018). In the group with <30% stenosis, the LV wall thickness/cavity area ratio (mean ± SEM) increased from 1.6 ± 0.2 mm/cm2 in men drinking <12 g/day to 6.2 ± 1.4 mm/cm2 in men drinking 72–180 g/day (p= 0.021). A similar trend was seen in men with 30–60% coronary stenosis (p= 0.32). By contrast, in men with >60% coronary stenosis, the LV wall thickness/cavity area ratio decreased with increasing daily alcohol use from 2.2 ± 0.3 to 1.4 ± 0.1 mm/cm2 (p= 0.27).Conclusions: CAD modulates the effects of alcohol on the heart muscle. Heavy drinking results in concentric LV remodelling in men with no or only mild coronary artery stenoses whereas an opposite trend is seen in men with severe coronary artery obstructions. The mechanism of the interaction remains unknown.
Third Trimester Binge Ethanol Exposure Results in Fetal Hypercapnea and Acidemia but Not Hypoxemia in Pregnant Sheep
Authors: Cudd Timothy A. , Chen Wei‐Jung A. , Parnell Scott E. , West James R. 
Published: April 2006

Background: The mechanisms by which maternal ethanol abuse during pregnancy causes neurodevelopmental injury in the fetus are not well understood. The purpose of this study was to use a chronically instrumented fetal sheep model system to determine if a binge pattern of ethanol e‐posure administered throughout the third trimester reduced fetal arterial partial pressure of o‐ygen (PaO2); a positive finding would support the hypothesis that fetal hypoxemia may play a role in mediating ethanol‐related birth defects.Methods: Pregnant ewes received saline or 0.75, 1.25, 1.5, or 1.75 g/kg of ethanol intravenously over 1 hr beginning on day 109 of gestation (term = 145 days) for 3 consecutive days per week followed by 4 days without e‐posure. The fetuses were surgically instrumented on day 113, and e‐periments were performed on days 118 or 132, the 6th and the 12th ethanol e‐posure, respectively.Results: Ethanol infusions resulted in peak blood ethanol concentrations of 80.8 ± 6.5, 182.5 ± 13.5, 224.4 ± 13.9, and 260.6 ± 20.0 mg/dl ± SEM (maternal) and 70.0 ± 5.9, 149.7 ± 9.0, 216.9 ± 14.0, and 233.3 ± 19.8 mg/dl ± SEM (fetal) in response to the 0.75, 1.25, 1.5, and 1.75 g/kg doses, respectively. Maternal and fetal heart rate and maternal blood pressure increased whereas fetal blood pressure decreased in a dose‐dependent manner in response to ethanol infusions. Maternal and fetal arterial pH decreased and arterial partial pressures of carbon dio‐ide increased in response to ethanol infusions. Maternal PaO2 decreased whereas fetal PaO2 did not change in response to ethanol infusions.Conclusions: A binge ethanol e‐posure paradigm, three consecutive days per week throughout the third trimester at ethanol doses that created blood ethanol concentrations commonly achieved by human ethanol abusers, resulted in changes in maternal and fetal heart rate, changes in blood pressure, hypercapnea, acidemia, and maternal, but not fetal, hypo‐emia. We conclude that in an ovine model system, ethanol doses that create blood ethanol concentrations as high as 260 mg/dl do not result in fetal hypo‐emia. Remaining issues to address with this model system are whether neurodevelopmental injuries that are associated with maternal ethanol abuse are mediated by a reduction in fetal cerebral blood flow, fetal hypercapnea, or acidemia.
Identifying Maternal Self‐Reported Alcohol Use Associated With Fetal Alcohol Spectrum Disorders
Authors: Barr Helen M. , Streissguth Ann P. 
Published: April 2006

Background: The incidence of Fetal Alcohol Syndrome (FAS) has been estimated at 1 to 3 per 1000 live births. Fetal Alcohol Spectrum Disorders (FASD) (which include FAS) are estimated to occur in about 1 in 100 births. Cessation of drinking during pregnancy can improve the outcome even if the unborn child is already affected. For individuals born with FASD, an early diagnosis appears to be a protective factor against secondary disabilities. A quick screening tool to identify newborn children at risk has been elusive.Methods: A simple descriptive presentation is offered that shows where 36 individuals with FASD were found from among the many patterns and amounts of prenatal alcohol use that were reported by a sample of 1439 pregnant women whose offspring were later e‐amined within the first 7 years of life.Results: Individuals with FASD (i.e., those with FAS, fetal alcohol effects, alcohol‐related neurodevelopmental disorder) were found within two aggregates of alcohol scores that together recommend a set of three to four alcohol questions. Within this derivation sample, one scoring of the questions yields almost 78% sensitivity and 97% specificity for FASD. Another scoring of the same instrument yields 100% sensitivity with 90% specificity.Conclusions: These new data may facilitate early identification of offspring who may be most in need of early intervention, namely those born with FASD.
The Synthesis and Secretion of Fatty Acid Ethyl Esters From HepG2 Cells Are Stimulated by Lipoproteins and Albumin
Authors: Hasaba Ali , Laposata Michael 
Published: April 2006

Background: Fatty acid ethyl esters (FAEEs) are nonoxidative metabolites of ethanol produced by the esterification of fatty acids and ethanol. FAEEs have been implicated as mediators of ethanol‐induced organ damage in vivo and in vitro. They are detectable in the blood and in many organs after ethanol ingestion, and on this basis they are useful markers of ethanol intake in living patients as well as subjects at autopsy. FAEEs found in human plasma after ethanol ingestion bind to lipoproteins and albumin.Methods: In this study, we used a hepatoblastoma cell model (HepG2) to determine if lipoproteins or albumin stimulates the synthesis and/or secretion of FAEEs from HepG2 cells. Because FAEEs have been shown to decrease HepG2 cellular proliferation and protein synthesis, their removal from cells potentially could reestablish normal cell activity.HepG2 cells were incubated with 100 mM ethanol and 6 nM 3H oleic acid to generate 3H‐FAEEs within the cells. Dose response and time course studies were performed by using low density lipoproteins, high density lipoproteins, and albumin as FAEE acceptors.Results: The results indicate that FAEEs are extracted efficiently by each of these FAEE carriers and that FAEE synthesis also is stimulated by the addition of FAEE carriers to the extracellular medium.Conclusion: These observations indicate that lipoproteins and albumin can extract ethyl esters from HepG2 cells and thereby may limit alcohol‐induced liver damage.
Effects of Acamprosate on Ethanol‐Seeking and Self‐Administration in the Rat
Authors: Czachowski Cristine L. , Legg Brooke H. , Samson Herman H. 
Published: April 2006

Background: Acamprosate (calcium acetyl homotaurinate) has been used clinically to treat relapse in alcoholics. In rats, it has been shown to decrease ethanol, but not water, self‐administration after ethanol deprivation.Methods: To further investigate the effect of acamprosate on reinforced behaviors in rats, the present experiment used: (1) both ethanol and sucrose reinforcer solutions to better assess the distinct effects of acamprosate on ethanol‐directed behaviors, and (2) an operant model that procedurally separates the “cost” to begin drinking from consuming the reinforcer solutions to dissociate the effects of acamprosate on appetitive versus consummatory processes. In daily sessions (5 days/week), rats (n= 6/group) were trained to make 30 lever‐press responses to gain access for 20 min to a sipper tube containing either ethanol (10%) or sucrose (3%). After stable responding, acamprosate treatment was given. Three doses were tested (50, 100, and 200 mg/kg/injection, intraperitoneally), one dose per week. Each week, a total of four injections were given (21 and 2 hr before the operant sessions over 2 consecutive days).Results: At these doses, acamprosate had no effect on the measures of appetitive responding for either solution. However, all doses reliably decreased ethanol consumption on the 2nd day of treatment (from an average of 0.83 to 0.63 g/kg). Analysis of the pattern of ethanol consumption showed that the effects of acamprosate occurred after the onset of a normal pattern of intake, as measured by lick rate and size of the initial bout of drinking, which suggested that acamprosate is most effective when combined with the pharmacological effects of ethanol. Sucrose intake was unaffected by all acamprosate treatments, which indicated that the treatment effects were specific to ethanol and not due to a general decrease in consummatory behavior.Conclusions: Overall, these results suggest that acamprosate is effective at reducing total ethanol intake, but may not reliably alter subjects propensity to begin a drinking bout as measured by this model. However, whether this applies to the clinical use of acamprosate, where other types of reinforcement may also precipitate relapse drinking, is not certain.
Ethanol‐Induced Increased Surface‐Localized Fibrinolytic Activity in Cultured Human Endothelial Cells: Kinetic Analysis
Authors: Abou‐Agag Laila H. , Tabengwa Edlue M. , Tresnak Jennifer A. , Wheeler Crystal G. , Taylor Kenneth B. , Booyse Francois M. 
Published: April 2006

Background: Moderate alcohol consumption is associated with reduced risk for coronary heart disease and this cardioprotection may be due, in part, to increased fibrinolysis. We have previously demonstrated that low concentrations of ethanol (0.1%, v/v) induce the short‐term (<1 hr) and sustained, long‐term (24 hr) increase in surface‐localized fibrinolytic activity; it up‐regulates t‐PA, u‐PA, and the candidate plasminogen receptor (PmgR), annexin II, and gene transcription in cultured human umbilical vein endothelial cells (HUVECs). These studies describe the short‐ and long‐term effects of low concentrations of ethanol on the kinetics of cell‐bound 125I‐labeled Glu‐plasminogen (Glu‐Pmg) activation by receptor (R)‐bound t‐PA, resulting in increased fibrinolytic activity in cultured HUVECs.Methods: Live cultured HUVECs were incubated with varying concentrations of Glu‐Pmg (0.25–2 μM) and ethanol (0.025–0.1%, v/v) (in the presence of Aprotinin and α2‐antiplasmin) and the direct activation of cell‐bound 125I‐labeled Glu‐Pmg quantitated by measurement of 125I‐labeled Mr 20 kDa plasmin light‐chain, after reduction/SDS‐PAGE. The effects of ethanol on 125I‐labeled Glu‐Pmg and t‐PA ligand binding were determined by Scatchard analysis (Bmax, sites/cell).Results: Cell‐bound t‐PA (endogenous/exogenous) activation of cultured HUVEC‐bound 125I‐labeled Glu‐Pmg (short‐ and long‐term) obeyed Michaelis‐Menten kinetics, both in the absence/presence of low ethanol, as shown by Lineweaver‐Burke plot analysis. In the short‐term, ethanol (at 0.1%) increased the Vmax (2.5‐fold), kcat (2‐fold) and the apparent kcat/Km (4‐fold), commensurate with a significant decrease in the apparent Km (6‐fold) and increase in 125I‐labeled Glu‐Pmg ligand binding, Bmax (2‐fold). In the long‐term, ethanol increased the Vmax (2‐ to 3‐fold), kcat (2.5‐fold), apparent kcat/Km (5‐fold), and B max (2‐fold) for 125I‐labeled Glu‐Pmg ligand binding, without significantly affecting the apparent Km.Conclusions: Low concentrations of ethanol induce the short‐ versus long‐term increase in surface‐localized fibrinolytic activity in cultured HUVECs via different mechanisms. Short‐term effects may be mediated by ethanol‐induced membrane conformational changes that simultaneously facilitate increased surface‐localized HUVEC PmgR availability and fibrinolytic protein/receptor interactions, resulting in the increased affinity of t‐PA for Glu‐Pmg and the accelerated activation of Glu‐Pmg (increased Bmax, decreased apparent Km). The long‐term effects may be attributed primarily to the ethanol‐induced increased availability of both newly synthesized t‐PA and PmgR and, hence, the accelerated activation of Glu‐Pmg (increased Bmax)
Altered Emotional Perception in Alcoholics: Deficits in Affective Prosody Comprehension
Authors: Monnot Marilee , Nixon Sara , Lovallo William , Ross Elliott 
Published: April 2006

Background: Affective prosody is a nonlinguistic aspect of language that conveys emotion and attitude during discourse. It is a dominant function of the right hemisphere. Because skills associated with the right hemisphere have been found to be impaired in alcoholics, this study explored the possibility that affective prosodic functioning may be sensitive to the effects of alcohol due to heavy persistent drinking or prenatal exposure.Methods: Subjects were aged 25 to 58 years. Twenty‐nine men and three women who met DSM‐IV criteria for an alcohol use disorder with a median of 39 days of sobriety, 11 men with a probable history of fetal alcohol exposure (FAexp), and 41 age‐matched control subjects of both sexes were tested by using the Aprosodia Battery. This instrument assesses affective prosodic comprehension (APC) across a range of verbal articulatory demands.Results: The alcoholic group scored 2 SD below the control mean, and the FAexp group scored −5 SD regardless of whether they had ever been diagnosed with alcohol abuse. Despite their poor performance on APC, alcoholic and FAexp groups performed similarly to the control group on vocabulary, abstract reasoning, and an index of cognitive impairment that used the Shipley Institute of Living Scale. Multiple regression analyses that used nine alcohol use variables to model APC resulted in four significant contributors to the effect. These regressors were related to early exposure to ethanol and chronicity of alcohol abuse.Conclusions: Alcoholics and FAexp subjects were significantly less accurate at APC compared with controls. These alcohol‐exposed subjects appear to be deficient in the ability to understand emotional valence in the speech of others, which results in errors of judgment that may impair social interactions.
Induction of Steady‐State Blood Alcohol Levels: Application to the Study of Within‐Session Alcohol Tolerance in Rats
Authors: Froehlich J. C. , Stewart R. B. , Li T.‐K. , Mosemiller A. K. , McCullough D. E. , Ho M. C. , Kisner J. M. 
Published: April 2006

Background: The study of within‐session alcohol tolerance in the rat has been hampered by methodological difficulties related to the measurement of dependent variables at predictable blood alcohol concentrations (BAC) during a single session of alcohol exposure. This study characterizes a method for maintaining steady‐state blood alcohol levels over several hours in the rat, referred to as the “alcohol clamp.”Methods: Wistar rats were implanted with an indwelling catheter in the carotid artery for blood sampling and another in the external jugular vein for alcohol infusion. To clamp BAC at a predetermined level, rats first were infused with a priming dose of alcohol to establish the desired or “target” BAC, followed by a continuous infusion of alcohol at a rate equal to that of alcohol metabolism in the rat. This maintained BAC at a constant level over time. BACs of 100, 200, or 300 mg% were maintained over several hours in separate groups of rats. The alcohol clamp was applied to the study of acute (within‐session) alcohol tolerance in rats selectively bred for high and low alcohol drinking. Alcohol‐induced hypothermia was used to index tolerance, and within‐session alcohol tolerance was defined as a return of body temperature toward baseline during the course of the alcohol infusion while BAC was maintained at a constant level.Results: The continuous alcohol infusion procedure maintained BAC in a steady state throughout the 3 hr alcohol infusion session at each of the three target BAC levels. Alcohol infusion induced a drop in body temperature, followed by a return of temperature toward baseline during the course of infusion, which indicated the development of within‐session alcohol tolerance.Conclusions: The continuous alcohol infusion procedure (alcohol clamp) maintained BAC in a steady state, both within and between subjects, across a wide range of blood alcohol levels. The alcohol clamp appears to be a useful tool for subsequent studies of within‐session alcohol tolerance in the rat.
Long‐Term Follow‐Up of a High School Alcohol Misuse Prevention Program's Effect on Students' Subsequent Driving
Authors: Shope Jean T. , Elliott Michael R. , Raghunathan Trivellore E. , Waller Patricia F. 
Published: April 2006

Background: Alcohol‐related injuries, particularly motor vehicle, are an important cause of adolescent mortality. School‐based alcohol prevention programs have not been evaluated in terms of driving outcomes. This study examined the effects on subsequent driving of a high school‐based alcohol prevention program.Methods: The Alcohol Misuse Prevention Study included a randomized test of the effectiveness of an alcohol misuse prevention curriculum conducted among 4635 10th‐grade students. Students were assigned to intervention (n= 1820) or control (n= 2815) groups and were followed for an average of 7.6 years after licensure, which typically occurred during or shortly after 10th grade. Outcomes examined included alcohol‐related and other serious offenses, and at‐fault, single‐vehicle, and alcohol‐related crashes.Results: Only serious offenses (which included alcohol‐related) had a significant treatment effect (statistically marginal) after we adjusted for sex, age, race, alcohol use/misuse, family structure, presence of prelicense offenses, age of driver licensure, and parental attitudes toward teen drinking. The effect was found only during the first year of licensure (estimated adjusted relative risk = 0.80, confidence interval = 0.63–1.01). Two first‐year serious offense interactions were found. The positive effect was strongest among the largest subgroup of students, those who were drinking less than one drink per week on average before the curriculum, compared with those who drank more than one drink per week (p= 0.009). The effect was also stronger for the small subgroup of students whose parents had not expressed disapproval of teens’ drinking, compared with those whose parents had disapproved (p= 0.004).Conclusions: These findings suggest that a high school‐based alcohol prevention program can positively affect subsequent driving, particularly that of students who do not use alcohol regularly. The results highlight the need to start prevention efforts early and extend them beyond the initial exposure to driving. Programs should incorporate the differing backgrounds of the students.
Course of DSM‐IV Alcohol Dependence in a Community Sample: Effects of Parental History and Binge Drinking
Authors: Hasin Deborah , Paykin Andrea , Endicott Jean 
Published: April 2006

Background: The role of positive family history in the etiology of alcohol dependence has been demonstrated repeatedly but little is known about the effect of this risk factor on the chronicity of alcohol dependence once it has begun.Methods: We studied the effects of parental and sibling history in conjunction with frequency of binge drinking in a sample of 169 community residents who met criteria for DSM‐IV alcohol dependence at the baseline interview. Subjects were re‐interviewed approximately 1 year later and the status of their alcohol‐dependence disorders (remitted or chronic) was determined.Results: Parental history of alcoholism was significantly related to chronicity of alcohol dependence, as was frequency of binge drinking.Conclusions: Failure to find an effect for family history on chronicity would have suggested that the effect was transient, perhaps interacting with time‐limited environmental vulnerability. The finding of a positive relationship between family history and chronicity suggests that the relationship between familial/genetic background and alcohol dependence is stable.