bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ethyl Glucuronide Discloses Recent Covert Alcohol Use Not Detected by Standard Testing in Forensic Psychiatric Inpatients
Authors: Wurst Friedrich Martin , Vogel Rüdiger , Jachau Katja , Varga Arthur , Alling Christer , Alt Andreas , Skipper Gregory E. 
Published: November 2003

Background: Considerable lives and money could be saved if one could detect early stages of lapsing/relapsing behavior in addicted persons (e.g., in safety‐sensitive workplaces) and could disclose harmful drinking in social drinkers. Due to the serious public health problem of alcohol use and abuse worldwide, markers of alcohol use have been sought. Both ethyl glucuronide (EtG) and phosphatidyl ethanol (PEth) appear to have high sensitivity and specificity and a time frame of detection that may elucidate alcohol use not detected by standard testing. Our aim was to assess their potential for detecting recent covert alcohol use under controlled conditions.Methods: Thirty‐five forensic psychiatric inpatients in a closed ward who had committed a substance‐related offense (§64 StGB), were followed for 12 months. The complete time spectrum of possible alcohol consumption was covered by the complementary use of breath and urinary ethanol (hours), urinary EtG (days), %carbohydrate‐deficient transferrin (CDT)/PEth (weeks), and γ‐glutamyltranspeptidase (GGT)/mean corpuscular volume (MCV) (weeks‐months).Results: Fourteen of the 146 urine samples examined were positive for EtG. In all EtG‐positive cases, patients reported alcohol consumption of between 40 and 200 g of ethanol 12–60 hr prior to testing. Urinary and breath ethanol were positive in only one case. In the blood samples, PEth was not positive in any case and %CDT did not exceed the reference value. Isoelectric focusing showed no abnormal Tf subtypes.Conclusions: The findings emphasize the diagnostic and therapeutic usefulness, specificity, and sensitivity of EtG as a marker of recent alcohol use. Such a test is needed in numerous settings, including alcohol and drug treatment (to detect lapse/relapse), in safety‐sensitive work settings where use is dangerous or in other settings where use may be inappropriate (e.g., such as driving, workplace, pregnancy, or monitoring physicians or other professionals who are in recovery and working), or for testing other groups (such as children or those with medical problems) where alcohol use would be unhealthy or unsafe. The health, social and socioeconomic benefits arising from the future use of these markers is hard to overestimate.
Reduced Olfactory Sensitivity, Discrimination, and Identification in Patients With Alcohol Dependence
Authors: Rupp Claudia I. , Kurz Martin , Kemmler Georg , Mair Dolores , Hausmann Armand , Hinterhuber Hartmann , Fleischhacker W. Wolfgang 
Published: November 2003

Background: Various olfactory deficits have been reported in the alcohol‐induced amnestic syndrome (Korsakoff's syndrome). Less is known about olfactory functioning in nonamnesic and nondemented alcoholic patients.Methods: Olfactory performance of 30 alcohol‐dependent patients was assessed unirhinally using the Sniffin’ Sticks (threshold, discrimination, identification, composite TDI score) and compared with that of 30 healthy controls, matched for sex, age, and smoking status.Results: Patients showed significantly reduced olfactory sensitivity (higher threshold), discrimination, and identification compared with controls. No group differences were observed in laterality. Identification and discrimination group differences remained significant after controlling for differences in sensitivity. Olfactory deficits in patients were present independent of age, gender, and duration of abstinence (<3 months) and were not attributable to smoking or general cognitive abilities. More than half of the patients (56.7%) could be classified as hyposmic. Lower overall olfactory functioning (TDI) was associated with longer duration of a regular alcohol intake and higher values of γ‐glutamyltransferase (GGT).Conclusions: Olfactory dysfunction is common in nonamnesic and nondemented patients with alcohol dependence. Results suggest a detrimental effect of alcohol on central olfactory processing.
Alcohol Affects Executive Cognitive Functioning Differentially on the Ascending Versus Descending Limb of the Blood Alcohol Concentration Curve
Authors: Pihl Robert O. , Paylan Sheila S. , Gentes‐Hawn Alyson , Hoaken Peter N. S. 
Published: November 2003

Background: Executive cognitive functioning (ECF), a construct that includes cognitive abilities such as planning, abstract reasoning, and the capacity to govern self‐directed behavior, has been recently researched as an antecedent to many forms of psychopathology and has been implicated in alcohol‐related aggression. This study was designed to examine whether differential ECF impairments can be noted on the ascending versus the descending limbs of the blood alcohol concentration curve.Methods: Forty‐one male university students participated in this study. Twenty‐one subjects were given 1.32 ml of 95% alcohol per kilogram of body weight, mixed with orange juice, and the remaining 20 were given a placebo. Participants were randomly assigned to either an ascending or descending blood alcohol group and were tested on six tests of ECF on their assigned limb. Subjective mood data were also collected.Results: Intoxicated participants on both limbs demonstrated ECF impairment; the descending‐limb group showed greater impairment than their ascending‐limb counterparts. Intoxicated subjects were significantly more anxious at baseline than placebo subjects. The introduction of this covariate nullified any significant differences in subjective mood found on either limb of the blood alcohol concentration curve, but ECF impairments remained robust.Conclusions: Our results support the conclusion that alcohol negatively affects cognitive performance and has a differential effect on the descending versus the ascending limb of the blood alcohol concentration curve. The latter finding may have important ramifications relating to the detrimental consequences of alcohol intoxication.
Mecamylamine Attenuates the Subjective Stimulant‐Like Effects of Alcohol in Social Drinkers
Authors: Chi Henry , de Wit Harriet 
Published: November 2003

Background: Recent studies have implicated central nicotinic cholinergic receptor systems in the reinforcing properties of alcohol. In laboratory animals, mecamylamine, a central nicotinic receptor antagonist, reduces the consumption of and preference for alcohol. This study investigated the effect of mecamylamine on the subjective responses to alcohol in humans. It was hypothesized that mecamylamine (7.5 and 15 mg) would attenuate the stimulant‐like subjective effects of alcohol (0.8 g/kg) and decrease the self‐reported desire to consume additional alcohol beverages.Methods: Fourteen male and 13 female nonsmokers participated in 6 laboratory sessions. During each session, subjects received, in randomized order under double‐blinded conditions, a capsule containing mecamylamine (7.5 or 15 mg) or placebo followed by a beverage containing alcohol (0.8 g/kg) or placebo. Physiologic and subjective‐effect measures were taken at 30‐min intervals for 2 hr after beverage consumption.Results: Mecamylamine attenuated the stimulant and euphoric effects of alcohol and reduced the self‐reported desire to consume additional alcohol beverages. This effect was most pronounced in men, even though women exhibited greater physiologic reactions to mecamylamine.Conclusions: These findings suggest that nicotinic cholinergic receptors are involved in mediating some of the stimulant‐like effects of alcohol.
Neuropeptide Y Reduces Oral Ethanol Intake in Alcohol‐Preferring (P) Rats Following a Period of Imposed Ethanol Abstinence
Authors: Gilpin Nicholas W. , Stewart Robert B. , Murphy James M. , Li Ting‐Kai , Badia‐Elder Nancy E. 
Published: November 2003

Background: Intracerebroventricular infusion of NPY has been shown to reduce ethanol intake in alcohol‐preferring (P) rats in a limited access procedure. The purpose of the present investigation was to extend this finding to a two‐bottle free‐choice continuous access procedure in groups of rats that either did or did not undergo a period of imposed ethanol abstinence and ethanol reinstatement.Methods: In experiment 1, female P rats were given 6 weeks of continuous access to ethanol (8% w/v) and water. Ethanol was removed for a period of 2 weeks during which the rats were surgically implanted with a cannula into the lateral ventricle. Following the ethanol abstinence period and immediately before ethanol reinstatement, rats received a single infusion of either artificial cerebrospinal fluid or NPY (10 μg). Ethanol and water intake was measured at both 4 hr and 24 hr after infusion, and 24‐hr intake measures were taken daily for 13 postinfusion days. Experiment 2 was run in parallel with experiment 1, with the exception that rats did not undergo a period of imposed ethanol abstinence. Also, food intake was measured 4 and 24 hr after infusion.Results: Following 2 weeks of imposed ethanol abstinence (experiment 1), NPY suppressed ethanol intake through postinfusion day 2. After uninterrupted continuous access to ethanol (experiment 2), NPY suppressed ethanol intake to a lesser extent and this effect lasted only 24 hr. NPY increased food intake at the 4‐hr but not the 24‐hr measure.Conclusions: Previous findings that central administration of NPY suppresses ethanol intake in P rats are extended by this study to a continuous access procedure, and the effect is amplified following a period of imposed ethanol abstinence. This effect of NPY compares favorably to results obtained with other treatments tested in similar animal models and provides support for a role of NPY in an allostasis model of addiction.
A Polymorphism in the α4 Nicotinic Receptor Gene (Chrna4) Modulates Enhancement of Nicotinic Receptor Function by Ethanol
Authors: Butt Christopher M. , Hutton Scott R. , Stitzel Jerry A. , Balogh Seth A. , Owens Jeremy C. , Collins Allan C. 
Published: November 2003

Background: Several studies indicate that ethanol enhances the activity of α4β2 nicotinic acetylcholine receptors (nAChR). Our laboratory has identified a polymorphism in the α4 gene that results in the substitution of an alanine (A) for threonine (T) at amino acid position 529 in the second intracellular loop of the α4 protein. Mouse strains expressing the A variant have, in general, greater nAChR‐mediated 86Rb+ efflux in response to nicotine than strains with the T variant. However, the possibility of the polymorphism modulating the effects of ethanol on the 86Rb+ efflux response has not been investigated.Methods: We have used the 86Rb+ efflux method to study the acute effects of ethanol on the function of the α4β2 nAChR in the thalamus in six different mouse strains. Experiments were also performed on tissue samples taken from F2 intercross animals. The F2 animals were derived from A/J mice crossed with a substrain of C57BL/6J mice that carried a null mutation for the gene encoding the β2 nAChR subunit.Results: In strains carrying the A polymorphism (A/J, AKR/J, C3H/Ibg), coapplication of ethanol (10–100 mM) with nicotine (0.03–300 μM) increased maximal ion flux when compared with nicotine alone with no effect on agonist potency. In contrast, ethanol had little effect on the nicotine concentration‐response curve in tissue prepared from strains carrying the T polymorphism (Balb/Ibg, C57BL/6J, C58/J). Experiments with the F2 hybrids demonstrated that one copy of the A polymorphism was sufficient to produce a significant enhancement of nAChR function by ethanol (50 mM) in animals that were also β2 +/+. Ethanol had no effect on nicotine concentration‐response curves in T/T β2 +/+ animals.Conclusions: The results suggest that the A/T polymorphism influences the initial sensitivity of the α4β2 nAChR to ethanol.
Serotonin Transporter Gene Variation is Associated with Alcohol Sensitivity in Rhesus Macaques Exposed to Early‐Life Stress
Authors: Barr Christina S. , Newman Timothy K. , Becker Michelle L. , Champoux Maribeth , Lesch Klaus Peter , Suomi Stephen J. , Goldman David , Higley J. Dee 
Published: November 2003

Background: Decreased sensitivity to alcohol has been demonstrated to be a predictor of alcoholism in humans, and variation in the gene‐linked polymorphic region of the serotonin transporter (5‐HTTLPR) is associated with the response to the motor‐impairing effects of alcohol. In a nonhuman primate model of excessive alcohol intake, we have shown that decreased serotonin turnover is associated with both lower initial sensitivity to alcohol and higher prospective alcohol consumption using rhesus macaques. In addition, we have demonstrated that macaques separated from their mothers and reared in peer‐only groups are more likely to consume alcohol as adults.Method: To examine the relationship between serotonin transporter genotype, early rearing experience, and initial sensitivity to alcohol, peer‐ and mother‐reared, adolescent, alcohol‐naive rhesus macaques (n= 123) were rated for intoxication after intravenous administration of ethanol (2.2 g/kg and 2.0 g/kg for males and females, respectively) during two testing periods. Serotonin transporter (rh5‐HTTLPR) genotype was determined using polymerase chain reaction followed by gel electrophoresis, and data were analyzed using ANOVA and the Mann‐Whitney U test.Results: Our analyses demonstrate an effect of serotonin transporter gene variation on ethanol sensitivity, such that animals homozygous for the l allele exhibited decreased sensitivity to the ataxic and sedating effects of alcohol. This effect remained after correction for blood ethanol concentrations and birth cohort. When animals were segregated according to rearing condition, serotonin transporter gene variation predicted intoxication scores among peer‐reared animals.Conclusions: As in some human reports, this study demonstrates a diminution in the response to alcohol in animals homozygous for the l rh5‐HTTLPR allele. The phenotypic expression of this genotype in l/s animals, however, is environmentally dependent.
National Survey of Hepatocellular Carcinoma in Heavy Drinkers in Japan
Authors: Horie Yoshinori , Yamagishi Yoshiyuki , Kajihara Mikio , Kato Shinzo , Ishii Hiromasa 
Published: November 2003

Background: The major cause of hepatocellular carcinoma (HCC) in the general Japanese population is an infection related to hepatotropic viruses, especially hepatitis virus C (HCV). Even in heavy drinkers, the major cause of HCC is HCV infection. However, HCC without viral infection has been reported in heavy drinkers. Alcohol has been also reported to be associated with an increased risk of cancer. In this study, we investigated aspects of HCC pathogenesis in heavy drinkers in Japan.Methods: Questionnaires were sent to 1350 hospitals authorized by the Japanese Society of Gastroenterology. The questionnaires asked about the number of inpatients with the different types of alcoholic liver diseases, admitted to each hospital between 1998 and 2001.Results: The percentage of heavy drinkers among all admitted patients with liver diseases or liver cirrhosis was approximately 15%. Of the patients with alcoholic liver cirrhosis, the cirrhosis was derived from alcohol alone in 61% and from alcohol plus a virus in 39% of patients. Furthermore, the percentage of patients with alcoholic liver cirrhosis caused by alcohol alone and who did not have HCC was 80%. However, the percentage of HCC patients who tested negative for viral hepatitis serum markers was 27% of the total number of heavy drinkers admitted for HCC. A study mainly on liver cirrhosis performed in the early 1990s demonstrated that the alcohol‐alone group accounted for 44% of admitted patients with alcoholic liver cirrhosis and 18% of heavy drinkers admitted for HCC.Conclusions: Because the consumption of alcohol is increasing in Japan, the frequency and number of cases of alcoholic liver cirrhosis are increasing. Viral hepatitis infection, however, still plays an important role in hepatocarcinogenesis in heavy drinkers. Radiographical examination is recommended even in patients with alcoholic liver cirrhosis who test negative for serum markers of viral hepatitis.
Association Between γ‐Glutamyl Transpeptidase Activity and Status of Disorders Constituting Insulin Resistance Syndrome
Authors: Yokoyama Hirokazu , Moriya Susumu , Homma Yasuhiko , Ogawa Tetsuhei 
Published: November 2003

Background:Serum γ‐glutamyl transferase (γGTP) activity is a well‐established marker of alcohol consumption. However, recently, a correlation between serum γGTP activity and insulin resistance status has been demonstrated.Methods:To determine whether serum γGTP activity could be associated with the status of various disorders caused by increased insulin resistance levels, namely, insulin resistance syndrome, a cross‐sectional study for 11,884 Japanese men was performed. They were divided into three groups by their age, and associations between γGTP and various indexes of insulin resistance syndrome were studied by multiple logistic regression analysis in which subjects' drinking styles were corrected for in each age bracket.Results:Consuming ethanol more than 40 g/day, body mass index more than 25.9 kg/m2, and triglyceride levels more than 150 mg/dl were significant risk factors accounting for increased γGTP activity (more than 78 IU/liters) irrespective of age. In addition, when subjects of 40 to 59 years old were selectively studied, hypertension, hypercholesteremia, hyperuricemia, and increased glycohemoglobin A1C levels were also significant risk factors for increased γGTP activity.Conclusions:There are significant associations between γGTP and the status of insulin resistance syndrome. In addition to excessive alcohol consumption, the status of insulin resistance syndrome could affect subjects' γGTP activities.
Correlation Between Insulin Resistance and γ‐Glutamyl Transpeptidase Sensitivity in Light Drinkers
Authors: Moriya Susumu , Yokoyama Hirokazu , Hirose Hiroshi , Ishii Hiromasa , Saito Ikuo 
Published: November 2003

Background:Our previous studies suggested that serum γ‐glutamyl transpeptidase (GGTP) level was correlated with insulin resistance level estimated by the homeostasis model assessment in teetotalers and occasional drinkers. In the surveys, strong correlation between GGTP and triglyceride also was observed. This study examined whether the correlation held true for regular drinkers.Methods:Seven hundred and seventeen male subjects in annual health checkups were divided into three groups according to their drinking styles and further divided into four subgroups according to their serum GGTP levels. In the other surveys, they were ranked by their amount of ethanol consumption. The correlation between GGTP and insulin resistance level was studied in each group.Results:Single regression analysis and analysis of variance showed that GGTP level was significantly correlated with insulin resistance level as determined by the homeostasis model assessment, as well as with triglyceride level regardless of subjects' drinking styles. The associations were confirmed by multiple regression analyses in which age, levels of uric acid, total cholesterol, high‐density lipoprotein cholesterol, and body mass index were adjusted, at least in nondrinkers or light drinkers. However, the multiple regression analyses indicated that the association between GGTP and insulin resistance level was not significant in subjects who take ethanol more than five times per week. The studies according to the amount of subjects' ethanol consumption indicated that the association between GGTP and insulin resistance was significant in the subjects who take ethanol up to 280 g/week.Conclusion:Individual variation in insulin resistance status may contribute to individual variations of sensitivity of GGTP to ethanol intake, at least in light drinkers.
Ethanol Induces Transforming Growth Factor‐α Expression in Hepatocytes, Leading to Stimulation of Collagen Synthesis by Hepatic Stellate Cells
Authors: Kato Junji , Sato Yasuhiro , Inui Noriaki , Nakano Yoichiro , Takimoto Rishu , Takada Kohich , Kobune Masayoshi , Kuroiwa Ganji , Miyake Sachie , Kohgo Yutaka , Niitsu Yoshiro 
Published: November 2003

Background: Liver fibrosis often develops in alcoholic liver diseases without accompanying inflammation; however, the underlying mechanism is unclear. Using ethanol‐exposed human HepG2 hepatoblastoma cells as a model for alcoholic liver diseases, we previously found that ethanol exposure causes HepG2 cells to secrete a ∼6000 Da nonheparin‐binding polypeptide that stimulates collagen synthesis in human IMR‐90 fibroblasts. The aim of the current study was to characterize and identify this factor.Methods: Concentration of type I procollagen peptide and transforming growth factor (TGF)‐α was assessed by enzyme‐linked immunosorbent assay. TGF‐α protein expression was examined by Western blot. Type I collagen messenger RNA expression in rat hepatic stellate cells was assessed by reverse transcription‐polymerase chain reaction.Results: The collagen‐stimulating activity in conditioned media from ethanol‐exposed HepG2 cells to stimulate type I procollagen peptide synthesis of IMR‐90 cells was specifically inhibited by addition of anti‐TGF‐α antibodies. Western blot analysis showed increased TGF‐α protein expression in ethanol‐treated HepG2 cells. TGF‐α in conditioned medium from ethanol‐exposed HepG2 cells stimulated type‐I collagen messenger RNA expression in rat hepatic stellate cells.Conclusions: These results suggest that TGF‐α derived from ethanol‐exposed hepatocytes may contribute to the development of hepatic fibrosis in alcoholic liver diseases.
Association Analyses Between Polymorphisms of the Phase II Detoxification Enzymes (GSTM1, NQO1, NQO2) and Alcohol Withdrawal Symptoms
Authors: Okubo Takehito , Harada Shoji , Higuchi Susumu , Matsushita Sachio 
Published: November 2003

Background: NRH‐quinone oxidoreductase 2 (NQO2) along with glutathione S‐transferase M1 (GSTM1) and NAD(P)H‐quinone oxidoreductase 1 (NQO1), which is involved in phase II detoxification reactions, is thought to be important for detoxification of catechol o‐quinones in the central nervous system. Our previous study revealed that the human NQO2 gene is highly polymorphic. In this study, we investigated a possible association between polymorphisms of the GSTM1, NQO1, and NQO2 genes and alcohol withdrawal symptoms such as delirium tremens, hallucination, and seizure.Methods: A total of 247 Japanese male alcoholic patients with alcohol withdrawal symptoms or without the symptoms, and 134 age‐matched Japanese male controls (nonhabitual drinkers), were examined by using polymerase chain reaction (PCR), PCR restriction fragment length polymorphism, PCR‐based single‐strand conformational change polymorphism, and PCR direct sequencing analyses.Results: A significant difference was found between alcoholic patients and controls in genotype frequency at an insertion/deletion site in the promoter region of the NQO2 gene (p= 0.0014). The frequency of the homozygous genotype for the D allele at this locus was significantly higher in delirium tremens‐positive patients (p= 0.0004) and in hallucination‐positive patients (p= 0.0001), and in patients displaying both delirium tremens and hallucination (p= 0.0002), than in controls. The values were still significant after Bonferroni correction. On the other hand, no significant difference was detected for allele frequencies or genotype frequencies for the other polymorphic loci of the NQO2 gene. Moreover, GSTM1 gene deletion and missense mutation (Pro187Ser) of the NQO1 gene showed no significant association with alcohol withdrawal symptoms.Conclusion: Present data suggest that an insertion/deletion polymorphism in the promoter region of the NQO2 gene plays an important role in the pathogenesis of alcoholism and alcohol withdrawal symptoms.