bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variations on the CAGE Alcohol Screening Questionnaire: Strengths and Limitations in VA General Medical Patients
Authors: Bradley Katharine A. , Kivlahan Daniel R. , Bush Kristen R. , McDonell Mary B. , Fihn Stephan D. 
Published: April 2006

Background: Several variations on the CAGE alcohol screening questionnaire have been recommended. This report evaluates modifications and additions to the CAGE.Methods: Alcohol screening questionnaires were evaluated in male VA general medicine patients (n= 227; mean age, 65.8). Mailed questionnaires included two scoring options for the CAGE (standard and last‐year time frames), questions about quantity and frequency of drinking, two questions about episodic heavy drinking, and the question “Have you ever had a drinking problem?” Main analyses compared alcohol screening questions, at various cut‐points, to a gold standard of hazardous drinking during the past year (≥14 drinks/week or ≥5 drinks on an occasion) and/or DSM‐III‐R alcohol abuse or dependence, based on standardized interviews.Results: The CAGE questionnaire with a past‐year time frame was much less sensitive (0.57 vs. 0.77) but more specific (0.82 vs. 0.59) than the standard CAGE for detecting hazardous drinking during the past year and/or DSM‐III‐R alcohol abuse or dependence. An eight‐item questionnaire that included the standard CAGE was most sensitive (0.92) but had low specificity (0.50). A single question about the frequency of drinking ≥6 drinks on an occasion, included in the eight‐item questionnaire, was both relatively sensitive (0.77) and specific (0.83).Conclusion: The CAGE questionnaire with a past‐year time frame was an insensitive alcohol‐screening test. An eight‐item augmented version of the standard CAGE was the most sensitive. A question about the frequency of drinking ≥6 drinks on an occasion performed better than the standard CAGE, which made it the optimal brief screening test for at‐risk drinking.
Acute Effects of Ethanol on Steroidogenic Acute Regulatory Protein (StAR) in the Prepubertal Rat Ovary
Authors: Srivastava Vinod K. , Hiney Jill K. , Dearth Robert K. , Dees W. Les 
Published: April 2006

Background: Steroidogenic acute regulatory protein (StAR) is a 30 kDa mitochondrial protein that plays an essential role in steroid hormone biosynthesis by facilitating delivery of cholesterol across the mitochondrial membrane, where side chain cleavage occurs to initiate ovarian steroidogenesis. Because ethanol (EtOH) suppresses estradiol secretion in prepubertal female rats, we evaluated the effects of EtOH on prepubertal ovarian StAR.Methods: At 0700 hr, 28‐day‐old female rats were gavaged with saline or a 3 g/kg dose of EtOH. At 0800 hr, half of each of these two groups was treated with 15 IU of pregnant mare serum gonadotropin (PMSG). At 1000 hr, a 2 g/kg dose was administered to maintain moderately elevated blood alcohol levels. At 1600 hr, all of the animals were killed by decapitation, and blood and ovaries were collected for measurement of serum pregnenolone and estradiol and for ovarian StAR gene and protein expression.Results: Northern blot analysis showed two major transcripts of 3.8 and 1.7 kb of ovarian StAR mRNA. The ovaries from EtOH‐treated rats showed decreased (p < 0.01) basal expression of both 3.8 and 1.7 kb StAR transcripts. PMSG‐stimulated animals showed a more than 4‐fold increase (p < 0.001) in the levels of both transcripts, when compared with ovaries from animals that received saline or EtOH only. Conversely, in EtOH‐treated animals, the PMSG‐stimulated expression of the 1.7 kb transcript was blocked, and the increase in the 3.8 kb StAR transcript was blunted (p < 0.05 vs. PMSG). Western blot analysis revealed that EtOH exposure also depressed (p < 0.01) the basal expression of StAR protein. PMSG‐stimulated animals showed an increase (p < 0.001) in levels of StAR protein, and this was blocked (p < 0.01) by EtOH. These changes observed in ovarian StAR mRNA and protein were paralleled by changes in serum pregnenolone and estradiol. Specifically, acute EtOH exposure suppressed (p < 0.05) the basal levels of both steroids. Furthermore, PMSG‐stimulated animals showed an increase in the production of pregnenolone (p < 0.05) as well as estradiol (p < 0.01), and EtOH blocked this stimulatory action of PMSG on both steroids.Conclusion: These results demonstrate for the first time that EtOH is capable of altering ovarian StAR expression, which contributes to the detrimental effect this drug has on ovarian steroidogenesis during prepubertal development.
A Retinoic Acid Receptor Antagonist Suppresses Brain Retinoic Acid Receptor Overexpression and Reverses a Working Memory Deficit Induced by Chronic Ethanol Consumption in Mice
Authors: Alfos Serge , Boucheron Catherine , Pallet Véronique , Higueret Denise , Enderlin Valérie , Béracochéa Daniel , Jaffard Robert , Higueret Paul 
Published: April 2006

Background: Chronic ethanol consumption induces disorders in the biosynthesis of retinoic acid, an active derivative of vitamin A. Recent evidence suggests that an alteration in the retinoic acid signaling pathway leads to impairments in learning and memory in adult mice. We have previously shown that chronic ethanol consumption in mice produces an increased expression of the brain retinoic acid receptor β (RARβ) mRNA. These results prompted us to examine whether suppressing the overexpression of retinoid receptors in alcohol‐treated mice by RAR antagonist administration would reverse their cognitive impairment.Methods: After 10 months of ethanol consumption (12% v/v in drinking water), C57BL/6 mice were submitted to a working memory task in a T‐maze. Then, mice of the control and the ethanol‐treated groups received an RARβ antagonist (CD2665 0.6 mg/kg) for 22 days. The behavioral effect of CD2665 administration was evaluated on a spontaneous alternation task and the neurochemical effect was measured by quantifying the mRNA expression of RARα, RARβ, retinoid X receptor (RXRβ/γ) and tissue transglutaminase (tTG; a retinoic acid‐target gene).Results: Mice submitted to ethanol treatment exhibited a progressive decrease in spontaneous alternation rates over successive trials. Moreover, these mice displayed an increased expression of brain RARβ and RXRβ/γ mRNA, together with an increased level of tTG mRNA and enzymatic activity. The administration of CD2665 to alcohol‐treated mice totally reversed the working memory deficit and suppressed the overexpression of brain RARβ, RXRβ/γ and tTG mRNA, whereas the same treatment in control mice decreased only the RARβ mRNA level without affecting memory performance.Conclusion: These data point to the potential role of the retinoid signaling pathway in memory processes and suggest that the overexpression of brain RARβ and RXRβ/γ could be responsible, at least in part, for some memory impairments observed during chronic ethanol consumption.
Bone Marrow Triglyceride Accumulation and Hormonal Changes During Long‐Term Alcohol Intake in Male and Female Rats
Authors: Wezeman Frederick H. , Gong Zhaodi 
Published: April 2006

Background: Chronic alcohol consumption may influence the metabolism of adipocytes, the most abundant stromal cell phenotype in bone marrow, and promote bone marrow triglyceride accretion.Methods: Male and female rats 35 days old were fed the Lieber‐De Carli liquid diet containing 36% of the calories as alcohol and were compared with pair‐fed rats given an isocaloric liquid diet in which maltose‐dextrin substituted for the calories supplied by alcohol. Other control rats were fed chow ad libitum. The rats were maintained on these diets for 64 days, after which the femurs were recovered and examined.Results: End weights of male and female alcohol‐fed rats were significantly lower than both control groups. Femur diaphyseal bone marrow triglyceride levels were significantly increased in alcohol‐fed male and female rats compared with both control groups. Femur bone marrow cavity diameters were significantly increased and cortical thickness was significantly decreased by alcohol in both males and females. Serum insulin levels were significantly decreased by alcohol only in female rats compared with the ad libitum but not the pair‐fed control group, and insulin‐like growth factor‐1 levels were significantly reduced in male and female rats given the alcohol diet compared with both controls. Male testosterone and female estradiol levels remained unchanged. Male estradiol levels were significantly increased by alcohol compared with both controls, and female progesterone levels were significantly reduced by alcohol compared with pair‐fed rats. Whereas female leptin levels were unchanged by alcohol, male leptin levels were significantly increased by alcohol compared with pair‐fed rats.Conclusions: Hormonal and growth factor changes during chronic alcohol consumption accompany triglyceride accumulation in diaphyseal bone marrow and may parallel the effects of alcohol on mesenchymal stem cells and the balance between osteogenic and adipogenic lineages and their cellular progenies.
ALDH2 Status, Alcohol Expectancies, and Alcohol Response: Preliminary Evidence for a Mediation Model
Authors: McCarthy Denis M. , Brown Sandra A. , Carr Lucinda G. , Wall Tamara L. 
Published: April 2006

Background: A genetic variant in the alcohol‐metabolizing enzyme (aldehyde dehydrogenase;ALDH2*2 allele), common in individuals of Asian heritage, has been associated with both physiologic response to alcohol and alcohol consumption. Prior research has also demonstrated that those with ALDH2*2 alleles have lower positive alcohol expectancies than those without these alleles. This preliminary study was designed to test whether the level of response to alcohol is the mechanism by which ALDH2 status may affect alcohol expectancies.Methods: Data were collected from 32 Asian American college students (14 women and 18 men). By use of a randomized, double‐blind design, participants were administered oral placebo and alcohol at separate laboratory sessions. Data included blood tests to establish ALDH2 status, questionnaire measures of demographic information and alcohol expectancy, and several physiologic measures collected after placebo and alcohol administration.Results: ALDH2 status was related to alcohol response measures for both men and women. ALDH2 status was also related to tension reduction expectancies for women and to expectancies for cognitive behavioral impairment for men. In the male sample, the ALDH2/expectancy relationship was fully explained by the level of response to alcohol.Conclusions: These results represent a first step in understanding the mechanisms by which genetic factors, such as ALDH2 status, can affect alcohol‐related learning.
Differential Expression of NPY and Its Receptors in Alcohol‐Preferring AA and Alcohol‐Avoiding ANA Rats
Authors: Caberlotto Laura , Thorsell Annika , Rimondini Roberto , Sommer Wolfgang , Hyytiä Petri , Heilig Markus 
Published: April 2006

Background: Central neuropeptide Y (NPY) is known to control feeding and stress responses. Recently, it has been suggested that NPY also has a role in regulation of alcohol consumption.Methods: NPY and NPY receptor expression in genetically selected alcohol‐preferring (AA), alcohol‐nonpreferring (ANA), and Wistar rats were investigated. Expression was assessed using in situ hybridization histochemistry with riboprobes specific for preproNPY, Y1, and Y2 receptors. Effects of central NPY administration on ethanol self‐administration were also examined in AA, ANA, and Wistar rats by using oral operant self‐administration.Results: NPY mRNA expression was higher in ANA than in both AA and Wistar rats in the hippocampal CA region and dentate gyrus, whereas AA and Wistar did not differ from each other. No differences in NPY expression were found in the other regions analyzed: cingulate cortex, medial nucleus of the amygdala, arcuate, and paraventricular nuclei of the hypothalamus. Y1 receptor mRNA expression did not differ between the three lines. Y2 expression was higher in the dentate gyrus of both AA and ANA rats than in Wistar subjects. In the medial amygdala, Y2 mRNA was reduced in the AA line, compared to both ANA and Wistar rats. NPY injected intracerebroventricularly (1.5–3.0 nmol) did not affect operant ethanol self‐administration in any of the three lines examined.Conclusion: The NPY system seems to differ in several respects between rat lines with different levels of alcohol preference. Differences observed within the hippocampus could be related to behavioral traits other than alcohol intake but it is also possible that elevated hippocampal expression of NPY in the ANA rats contributes to the low alcohol intake of this line. Aberrant NPY expression and/function within the amygdala complex could contribute to alcohol preference and constitute an anatomic substrate of the effects of NPY expression on alcohol intake observed previously in genetically modified animals.
Paternal Alcoholism and Toddler Noncompliance
Authors: Das Eiden Rina , Leonard Kenneth E. , Morrisey Sean 
Published: April 2006

Background: This study examined the effect of fathers’ alcoholism and associated risk factors on toddler compliance with parental directives at 18 and 24 months of age.Methods: Participants were 215 families with 12‐month‐old children, recruited through birth records, who completed assessments of parental substance use, family functioning, and parent‐child interactions at 12, 18, and 24 months of child age. Of these families, 96 were in the control group, 89 families were in the father‐alcoholic‐only group, and 30 families were in the group with two alcohol‐problem parents. Child compliance with parents during cleanup situations after free play was measured at 18 and 24 months. The focus of this paper is on four measures of compliance: committed compliance, passive noncompliance, overt resistance, and defiance.Results: Sons of alcohol‐problem parents exhibited higher rates of noncompliance compared with sons of nonalcoholic parents. Sons in the two‐alcohol‐problem parent group seemed to be following a trajectory toward increasing rates of noncompliance. Daughters in the two‐alcohol‐problem parent group followed an opposite pattern. Other risk factors associated with parental alcohol problems also predicted compliance, but in unexpected ways.Conclusions: Results indicate that early risk for behavioral undercontrol is present in the toddler period among sons of alcoholic fathers, but not among daughters.
Ethanol Inhibits Spontaneous Activity of Central Nucleus of the Amygdala Neurons but Does Not Impair Retention in the Passive‐Avoidance Task
Authors: Naylor Jennifer C. , Simson Peter E. , Gibson Benjamin , Schneider Allen M. , Wilkins Emily , Firestone Aaron , Choy Megan 
Published: April 2006

Background: Behavioral studies using pharmacological manipulations that increase neuronal activity of the central nucleus of the amygdala (CeA) have implicated the CeA in enhancement of memory modulation. To date, however, there has been a dearth of studies investigating the effect of a drug that decreases CeA activity on memory modulation—a drug that inhibits the neuronal activity of the CeA might be expected to impair memory modulation. To determine whether ethanol inhibits CeA activity and, if so, whether decreased CeA activity is associated with impairment of memory modulation, this study investigated the effect of ethanol on spontaneous single‐unit activity of CeA neurons and retention in the passive‐avoidance task.Methods: The effect of ethanol (0.35, 0.75, 1.5, 2.5 g/kg) was determined on spontaneously firing neurons in the CeA in urethane‐anesthetized rats by use of standard in vivo single‐unit electrophysiological recording techniques. Additionally, the effect of ethanol when administered immediately after training in a standard passive‐avoidance task was determined on retention the following day.Results: Ethanol profoundly inhibited spontaneous CeA firing rates in urethane‐anesthetized rats at all doses tested. Maximal inhibition was related to dose. Each dose of ethanol significantly inhibited CeA activity within 15 min of administration; within 35 min of administration, 0.75 g/kg of ethanol inhibited CeA activity by 65.2%, and the highest dose (2.5 g/kg) produced nearly complete suppression of CeA activity (81.3%). Although ethanol markedly inhibited CeA activity, these same doses of ethanol failed to impair retention in the passive‐avoidance task: 0.35, 0.75, 1.5, and 2.5 g/kg of ethanol, administered immediately after training, failed to alter latency to step‐through the following day.Conclusions: These results show that ethanol profoundly inhibits spontaneous CeA activity and suggest that inhibition of the CeA is not sufficient to impair retention in the passive‐avoidance task.
Alcohol Dehydrogenase‐2*2 Allele is Associated With Decreased Prevalence of Fetal Alcohol Syndrome in the Mixed‐Ancestry Population of the Western Cape Province, South Africa
Authors: Viljoen D.L. , Carr L.G. , Foroud T.M. , Brooke L. , Ramsay M. , Li T.K. 
Published: April 2006

Background: Fetal alcohol syndrome (FAS) is particularly common among the mixed‐ancestry population of the Western Cape Province of South Africa and occurs at a frequency of 0.0392–0.0429 (39.2–42.9 of 1000) among 5‐ to 9‐year‐old school entrants. While FAS is clearly caused by an environmental insult, studies in twins and mice support a significant genetic contribution to risk for FAS. It is likely that the development of FAS following excessive alcohol exposure is influenced by genetic factors in both the mother and the child. Known polymorphisms of the alcohol dehydrogenase‐2 (ADH2) gene resulting in isozymes with different alcohol oxidizing capacities were investigated as possible candidates for influencing the risk for FAS.Methods: Genotyping was undertaken for the ADH2 locus in 56 FAS‐affected children, their 56 mothers, and 178 control individuals of mixed ancestry from the same geographic region. The ADH2 alleles were analyzed for the three groups and the allele frequencies of the mother and FAS‐affected children were independently compared with the control group.Results: The ADH2*2 allele was found to be significantly more common in the control group than in the mothers of FAS‐affected children (p= 0.025 ± 0.004) and in the FAS subjects (p= 0.025 ± 0.004). The ADH2*3 allele frequency was low and was not significantly different between the groups.Conclusion: The ADH2*2 allele is significantly more common in control individuals, suggesting that it may either confer protection or be a marker for a protective effect against FAS among individuals of mixed ancestry in the Western Cape Province of South Africa.
Protein Binding of α‐Hydroxyethyl Free Radicals
Authors: Moncada Claudio , Israel Yedy 
Published: April 2006

Background: The auto‐oxidation of ethanol is likely to proceed via the initial formation of hydroxyethyl radicals (HERs), the one‐electron oxidation product. In the laboratory, HERs can be generated by the Fenton reaction (H2O2+ Fe+2) in the presence of ethanol. We report studies on the binding of HERs to serum albumin, generated under Fenton and non‐Fenton conditions.Methods: The generation of HER was determined by electron paramagnetic resonance spectroscopy. The formation of ethanol‐derived protein adducts was determined by 14C‐ethanol incorporation into serum albumin and by the binding of antibodies raised against HER adducts.Results: We report that serum albumin, used as a model protein, is an effective trapping agent of HERs. In addition, HER radicals covalently bind to albumin to form acid stable adducts. Unexpectedly, we found that under aerobic conditions, the incubation of 50 mM ethanol and phosphate buffer (which contains iron traces) in the absence of the Fenton reagent yields HER radicals as shown by electron paramagnetic resonance spectroscopy and the formation of acid stable protein adducts that are recognized by antibodies raised against HER radical adducts.Conclusions: Proteins (serum albumin used as a model) are avid trapping agents of HER. There are minimal requirements for the generation of HER, because in the presence of oxygen and a phosphate buffer that contains traces of iron, ethanol readily generates HERs. Thus, HER production is likely to occur in many tissues. The ability of proteins to bind this ethanol radical should be valuable in the diagnosis of alcohol abuse and may be relevant to some of the chronic effects of ethanol.
Carbohydrate Deficient Transferrin in Abstaining Patients With End‐Stage Liver Disease
Authors: DiMartini Andrea , Day Nancy , Lane Tonya , Beisler Amy T. , Amanda Dew Mary , Anton Raymond 
Published: April 2006

Background: Carbohydrate deficient transferrin (CDT), a biochemical marker of chronic alcohol consumption, is used by researchers and clinicians alike in a variety of populations. Levels of CDT may be affected by certain types of medical illnesses and conditions. Thus the interpretation of CDT results may need to be carefully examined in these populations. Because CDT is synthesized, glycosylated, and secreted by the liver, the use of CDT values in patients with liver disease has been an area of focused interest.Methods: We evaluated the CDT values of 79 abstaining patients with end‐stage liver disease. These patients were recruited from a liver transplant clinic while they were listed and waiting for transplantation. Patients were determined to be abstaining both by interview and by random blood alcohol levels in those with a diagnosis of alcoholic liver disease. The severity of the liver disease was categorized by the Child‐Pugh score. Correlations were determined between CDT values and liver enzymes, and Child‐Pugh scores and liver diagnosis.Results: Nearly 50% of the patients had a CDT value of 2.6% or above, indicating a clinically positive value. There were strong correlations between CDT and a number of biochemical and physical variables, most importantly the Child‐Pugh score (r= 0.52, p= 0.000). Specific liver diseases were not associated with absolute CDT values. However, patients with hepatitis C (HCV) had a significantly higher chance of having a clinically positive CDT compared with patients with other types of liver diseases.Conclusions: These results suggest that an elevated CDT value may not accurately represent alcohol consumption in patients with advanced liver disease. In fact, in such patients, the CDT may become a marker for the degree of liver impairment in alcoholic and nonalcoholic liver disease. CDT values should be viewed with caution in any patient with liver disease especially when the degree of cirrhosis reaches a Child‐Pugh score of C (total score of 10 or above).