bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic‐Intermittent Ethanol Exposure During Adolescence Prevents Normal Developmental Changes in Sensitivity to Ethanol‐Induced Motor Impairments
Authors: White Aaron M. , Bae Jon G. , Truesdale Melanie C. , Ahmad Sukaina , Wilson Wilkie A. , Swartzwelder H. Scott 
Published: April 2006

Background Recent evidence indicates that adolescent and adult rats are differentially sensitive to many of the acute effects of ethanol. Little is known about the neurobehavioral consequences of repeated ethanol exposure during adolescence relative to adulthood. In the present study we examined the impact of repeated ethanol exposure during adolescence and adulthood on subsequent sensitivity to ethanol‐induced motor impairments.Methods The tilting plane test was used to assess the impact of acute ethanol (3.0 g/kg) on motor coordination before (test 1), 2 days after (test 2), and 16 days after (test 3) a 20 day period of chronic‐intermittent ethanol (CIE; 5.0 g/kg intraperitoneally every 48 hrs for 20 days) or isovolumetric chronic‐intermittent saline (CIS) treatment in adolescent (postnatal (PD) 30) and adult (PD 70) rats.Results Adolescent subjects were less sensitive than adults to the effects of ethanol on motor coordination during test 1. Adolescent CIS‐treated subjects exhibited an increase in sensitivity to ethanol‐induced motor impairments that reached adult levels by test 2 (PD 51) and remained stable between test 2 and test 3 (PD 65). Adolescent CIE‐treated subjects did not exhibit this age‐related increase in sensitivity. In this group, the effects of acute ethanol remained unchanged across the three testing days. Adult CIE‐treated subjects exhibited a small degree of tolerance between test 1 and test 2 (PD 91) that was no longer evident during test 3 (PD 105). In adult CIS‐treated subjects, the effects of acute ethanol remained stable across the three testing days. Blood ethanol concentrations assessed during testing suggest that age‐related changes in sensitivity to ethanol‐induced motor impairments are not related to changes in ethanol metabolism.Conclusions The data suggest that CIE exposure during adolescence has a lasting impact on sensitivity to ethanol‐induced motor impairments. This effect might stem from a disruption of normal developmental processes.
Chronic Continuous Nicotine Exposure During Periadolescence Does Not Increase Ethanol Intake During Adulthood in Rats
Authors: Smith Andrew M. , Kelly Ryan B. , Chen Wei‐Jung A. 
Published: April 2006

Background Nicotine has been considered as the gateway drug, because many teenagers experience cigarette smoking before seeking out other drugs. By using an animal model system, we assessed the effects of chronic continuous nicotine exposure during periadolescence on ethanol intake during young adulthood.Methods Periadolescent Sprague‐Dawley rats (35 days old) were used at the beginning of this study. These animals received subcutaneous implantation of nicotine pellets (15 or 25 mg in 21‐day time‐release pellets) or placebo pellets (0 mg of nicotine) on postnatal day 35. Beginning on postnatal day 53, the animals received various concentrations of ethanol solution during their active period (5:00 PM to 9:00 AM) starting with 2% (v/v, 4 days), then 5% (5 days), 8% (6 days), and 10% (6 days). Between 9:00 AM and 5:00 PM of the same day, the ethanol solution was replaced by regular tap water. The amounts of ethanol solution and regular water were measured daily.Results The analyses showed that ethanol intake (grams per kilogram of body weight) in the nicotine 15 and 25 mg groups did not differ from that in the nicotine 0 mg group, and no sex difference was found in ethanol intake. However, ethanol intake was increased as a function of the treatment days.Conclusions The results showed that chronic continuous nicotine exposure during adolescence did not increase ethanol intake in rats during young adulthood.
Alcohol Intake and Future Incidence of Hypertension in a General Japanese Population: The Hisayama Study
Authors: Ohmori Susumu , Kiyohara Yutaka , Kato Isao , Kubo Michiaki , Tanizaki Yumihiro , Iwamoto Hiromitsu , Nakayama Keizo , Abe Isao , Fujishima Masatoshi 
Published: April 2006

Background The question remains as to whether light to moderate alcohol intake is associated with an increased risk of hypertension.Methods In 1978, a total of 1101 residents (433 men and 668 women) in a subrural community, Hisayama, in Japan, aged 40 years or more, with normal blood pressure, who were free from cardiovascular disease, were enrolled in a 10‐year follow‐up study. Inquiries regarding regular drinking were made in an interview based on a self‐administered questionnaire.Results During the follow‐up, 101 men and 166 women developed hypertension (blood pressure ≥140/90 mm Hg or use of antihypertensive drugs). The age‐adjusted incidence of hypertension among current male drinkers increased significantly even with a light intake of alcohol (<23 g of ethanol per day). In women, the incidence was also significantly higher in drinkers than in nondrinkers. In multivariate analysis, alcohol intake, in addition to age and body mass index, remained a significant independent risk factor for hypertension in men, but not in women. In men, all three categories of current drinking were found to be significant risk factors for the development of hypertension after adjustment for age and body mass index [relative risk (RR), 2.00; 95% confidence interval (CI), 1.07–3.76 for light drinking compared with nondrinking; RR, 2.60; 95% CI, 1.50–4.49 for moderate drinking (23–45 g per day); and RR, 2.24; 95% CI, 1.26–3.99 for heavy drinking (≥46 g/day)].Conclusions Our results suggest that alcohol intake, even light drinking, is a predictor of future hypertension among Japanese men.
Stress Response Caused by Chronic Alcohol Intake in Aged Rat Brain
Authors: Unno Keiko , Asakura Hiromi , Shibuya Yuka , Kaihou Masako , Fukatsu Hideto , Okada Shoji , Oku Naoto 
Published: April 2006

Background Chronic alcohol consumption may act as a cellular stressor for brain cells, as has been found for aging. In this study we examined one component of the cellular stress response (heat shock proteins) as a function of age and alcohol exposure. We have found that the level of constitutively expressed heat shock protein 70 (heat shock cognate 70, or Hsc70) increases in the aged rat brain. Among many heat shock proteins and molecular chaperones, Hsc70 might be important not only for the normal protein folding pathway but also for refolding of denatured proteins produced by mild and chronic stress.Methods Male Wistar rats that were 5.5 to 28.5 months old were fed a liquid diet that contained 5% (w/v) alcohol or a control diet for 6 weeks. The effects of alcohol consumption and aging on the expression of Hsc70 in the brain were investigated. The cytosol proteins in the 12,000 ×g supernatant fraction were heat‐treated at 42°C for 1 hr. After the heat treatment, proteins that transferred from the soluble to insoluble aggregated fraction were estimated as heat‐unstable proteins.Results In the 24‐ and 30‐month‐old rat brain, chronic consumption of alcohol increased levels of Hsc70 and heat‐unstable proteins. On the other hand, those changes were not detected in the younger rat brain.Conclusion Chronic alcohol intake causes a stress response in the aged rat brain. It is thought that the increased level of Hsc70 is brought about by an increase of denatured proteins.
Evidence in an International Sample of Alcohol‐Dependent Subjects of Subgroups With Specific Symptom Patterns of Antisocial Personality Disorder
Authors: Kovac Ilija , Mérette Chantal , Legault Lucie , Dongier Maurice , Palmour Roberta M. 
Published: April 2006

Background An earlier latent class analysis (LCA) of the symptoms of antisocial personality disorder in alcohol‐dependent subjects enrolled in the Montreal sample of the WHO/ISBRA Study on State and Trait Markers of Alcohol Use and Dependence suggested a three‐class qualitative solution. The present analysis of a larger, international WHO/ISBRA sample provides evidence of a four‐class solution with expanded symptomatic differentiation.Methods An unrestricted LCA of 15 antisocial behaviors expressed after 15 years of age was performed in 465 males with DSM‐IV diagnosis of alcohol dependence, from the Montreal center (n= 120, overlapping the previous LCA), Helsinki (n= 80), São Paolo (n= 145), Sapporo (n= 22), and Sydney (n= 98); subjects were of various races, were ascertained from various sources, and showed a wide range of social adjustment.Results Four latent classes that appeared to differ qualitatively were identified. For descriptive purposes, the classes are termed socially adjusted adults (SAA, n= 197), antisocial work‐adjusted adults (AWAA, n= 126), antisocial work‐maladjusted adults (AWMA, n= 120), and antisocial aggressive adults (AAA, n= 23). The AAA class had the earliest age of onset for alcohol dependence, which decreased across classes. Proportion of alcohol‐dependent first‐degree relatives was low in the SAA class (13.6%), moderate in the AWAA and the AWMA classes (20.8% and 18.7% respectively), and high in the AAA class (33.3%).Conclusions It is unknown if and to what extent racial, cultural, and ascertainment heterogeneity between collaborating centers might have influenced these analyses. The results presented here show qualitative differences among antisocial alcohol‐dependent individuals in job adjustment and aggressive behavior, but only the latter distinction was relevant to familial alcohol dependence. Moreover, both the aggressive class and socially adjusted class differed in familial loading for alcohol dependence from the remaining two antisocial classes. These data provide improved empirical support for qualitative differentiation of aggressive from nonaggressive antisocial alcohol‐dependent individuals and might also have nosological implications for antisocial personality disorder.
The Effect of Total Body Water on the Relationship Between Alcohol Consumption and Carbohydrate‐Deficient Transferrin
Authors: Martinez L. D. , Barón A. E. , Helander A. , Conigrave K. M. , Tabakoff B. 
Published: April 2006

Background Clinicians agree that alcoholism commonly is overlooked in their patients, and that treating the symptoms without directing therapy to the underlying cause at best delays an inevitable decline in the patient's general health and well‐being. The current analysis focused on carbohydrate‐deficient transferrin (CDT), a promising biological marker of dangerous alcohol consumption.Methods Included in our study were men (730) and women (613) from study sites in Canada, Brazil, and Japan. All subjects were participants in the WHO/ISBRA Study on State and Trait Markers of Alcoholism, who completed an extensive demographic, medical, and behavioral survey and provided blood samples for determination of CDT levels. ANOVA and χ2 test for equality were used to examine the effect of total body water (TBW) on the alcohol consumption/CDT relationship. To examine whether accounting for differences in TBW improved the diagnostic properties of CDT when used as a state marker for alcohol consumption, odds ratios were calculated for men and women separately.Results Our results show that accounting for individual differences in TBW significantly influenced the alcohol consumption/CDT dose‐response relationship. The effect of TBW was different for men compared with women. When we used a consumption cutoff value of 40 g/day and the CDTect® recommended cutoffs (20 for men; 27 for women), adjusting for differences in TBW significantly increased diagnostic performance of CDT in men but not women.Conclusions The dependence of CDT measures on body water content needs to be taken into account to maximize the performance of CDT as an effective state marker of alcohol consumption in males.
Relationships Between Effects of Smoking, Gender, and Alcohol Dependence on Platelet Monoamine Oxidase‐B: Activity, Affinity Labeling, and Protein Measurements
Authors: Snell Lawrence D. , Glanz Jason , Tabakoff Boris 
Published: April 2006

Background Many studies have reported apparent associations between platelet monoamine oxidase (MAO) activity and susceptibility to alcoholism and other psychiatric conditions. Alcohol‐dependent individuals generally exhibit lower platelet MAO activity compared with controls, and on this basis, platelet MAO has been proposed as a potential genetic marker for predisposition to alcoholism. However, several lines of evidence also suggest that MAO activity is reduced in both the brain and platelets of smokers. Many alcohol‐dependent individuals are also tobacco users, and few studies have attempted to dissociate the effect of alcohol and tobacco use on MAO activity.Methods Platelet MAO‐B activity in 629 subjects recruited as part of the WHO/ISBRA Study of State and Trait Markers of Alcohol Use and Dependence was assayed by using a high throughput fluorescence assay. Platelet MAO‐B protein concentrations were measured by analysis of immunoblots probed with a polyclonal antibody selective for MAO. Quantitative measurements of affinity labeling of platelet MAO were made by using the selective MAO‐B catalytic site antagonist [3H]Ro 19–6327.Results Multiple regression analysis revealed that subjects’ gender, cigarette smoking, lifetime alcohol dependence, and recruitment site each contributed independently to the variance in platelet MAO activity levels. Female subjects had significantly higher MAO activity levels than males, whereas heavy smokers had significantly lower MAO activity levels than nonsmokers. Immunoblot measurement of platelet MAO‐B protein demonstrated that females had significantly higher MAO‐B protein concentrations. Platelet MAO‐B protein concentrations did not differ significantly between smokers and nonsmokers but were lower in subjects with a diagnosis of lifetime alcohol dependence (DSM‐IV) compared with subjects who were never alcohol dependent. Measurements of affinity labeling by [3H]Ro 19–6327 of platelet MAO correlated significantly with MAO activity levels (i.e., the lower MAO‐B activity in smokers was mirrored by lower levels of [3H]Ro 19–6327 binding).Conclusions In this international population, gender, cigarette smoking, lifetime history of alcohol dependence, and recruitment site were associated with lower platelet MAO activity levels. Differences in MAO activity associated with gender and lifetime alcohol dependence can be attributed largely to differences in MAO‐B protein concentration, whereas those associated with smoking behavior may be the result of binding of an inhibitor contained in cigarette smoke to platelet MAO‐B at catalytic site of MAO.
Heart Rate and Motor‐Activating Effects of Orally Self‐Administered Ethanol in Alcohol‐Preferring (P) Rats
Authors: Bell Richard L. , Rodd‐Henricks Zachary A. , Webster Amy A. , Lumeng Lawrence , Li Ting‐Kai , McBride William J. , Murphy James M. 
Published: April 2006

Background Autonomic and behavioral arousals often accompany reinforcement. Additionally, contextual cues associated with alcohol consumption elicit increases in heart rate in alcoholics. This study examined changes in heart rate (HR) and motor activity before and during limited‐access to ethanol, saccharin, or water in adult male alcohol‐preferring (P) rats.Methods Adult male P rats were implanted with radiotelemetric transmitters to measure HR and motor activity. The experiment involved placing the animals in a test chamber for a 90‐min pretest period, with water available. Thereafter, the animals were given a 90‐min test session with access to one of three test solutions: water, 0.0125% saccharin, or 15% (v/v) ethanol (EtOH). After a week of habituation (water served as the test solution for all three groups), the animals were given their respective test solution for 3 weeks.Results Analyses of HR revealed that the saccharin and EtOH groups had significantly higher HR than the water group during the pretest period of the third test week. Both the saccharin and EtOH groups had significantly higher HR than the water group during the test period of all three test weeks. Analyses of motor activity revealed that the EtOH group displayed higher motor activity than the water and saccharin groups during the pretest period of the third test week.Conclusions The data indicate that oral self‐administration of EtOH enhances behavioral and autonomic activation, compared with saccharin or water, in adult male P rats and support previous observations that changes in HR can be used as an index of reinforcement. Additionally, it seems that the behavioral and autonomic activation elicited by EtOH self‐administration can be conditioned to the environment in which EtOH was self‐administered. These findings parallel reports on cued reactivity (behavioral and autonomic activation) in alcoholics exposed to alcohol‐associated stimuli.
Executive Dysfunction and Clinical Outcome in Chronic Alcoholics
Authors: Moriyama Yasushi , Mimura Masaru , Kato Motoichiro , Yoshino Aihide , Hara Tsunekatsu , Kashima Haruo , Kato Akinobu , Watanabe Akiharu 
Published: April 2006

Background The purpose of this study was to investigate which of 12 neuropsychological tests predict alcoholic patients’ alcohol‐specific and/or alcoholic‐nonspecific outcome. Our hypothesis was that the ecologically valid neuropsychological tests that measure executive function are better predictors of alcoholics’ functional outcome.Methods We administered 12 neuropsychological tests to chronic alcoholics. Included in the tests were tasks of Reaction Time, Symbol Digit Modalities, Figure Position, Digit Span, Block Design, Trail Making, and six subtests of a battery called the Behavioral Assessment of the Dysexecutive Syndrome (BADS). Previous investigators have suggested that the BADS has ecological validity. Twenty‐two male alcoholics were compared with 15 nonalcoholic control subjects on these neuropsychological measures 7 weeks after detoxification. Two functional outcome indices, i.e., resumption of drinking and occupation, were evaluated 18 months after discharge.Results The total profile score and the score on three of the six subtests of the BADS were lower in alcoholics than in nonalcoholic controls. Alcoholics’ performance on the BADS predicted alcohol‐nonspecific outcome (occupation) but not alcohol‐specific (drinking) outcome. In contrast, other neuropsychological tests did not predict either of the two outcome indices.Conclusions The BADS total profile score is related to alcohol‐nonspecific outcome but not to alcohol‐specific outcome.
4‐Hydroxynonenal Detoxification by Mitochondrial Glutathione S‐Transferase Is Compromised by Short‐Term Ethanol Consumption in Rats
Authors: Chen Juanjuan , Schenker Steven , Henderson George I. 
Published: April 2006

Background 4‐Hydroxynonenal (HNE), a toxic lipid peroxidation product, has been implicated in mitochondrial damage in rat liver by ethanol consumption. The present study assessed the effects of short‐term in vivo ethanol exposure on HNE detoxification by mitochondrial glutathione S‐transferase (GST).Methods Male Sprague Dawley® rats were administered 5 doses of ethanol (4 g/kg) at 12 hr intervals by gavage. Pair‐fed rats that received isocaloric dextrose instead of ethanol served as controls. Mitochondrial and submitochondrial fractions were prepared from the livers. Mitochondrial contents of HNE and HNE‐glutathione conjugate were measured by high‐performance liquid chromatography. GST isoforms were identified by Western blots in submitochondrial fractions.Results Whereas there was an 80% increase in mitochondrial HNE content after ethanol consumption, there was a 42% decrease in the content of HNE‐glutathione conjugate, compared with controls (p < 0.05). After ethanol exposure, the GST activities toward HNE in intact mitochondria and in the membranous fraction were decreased by 37% and 45% (p < 0.05), respectively, whereas that in the aqueous fraction was unchanged. Kinetic analysis of HNE conjugation by the membrane‐associated GST showed that ethanol decreased the Vmax nearly by half (p < 0.05), whereas it did not affect the Km. HNE conjugation by the aqueous GST demonstrated a higher Km than that of the membrane‐associated GST, although its kinetics were not significantly altered by ethanol. Immunochemical analysis with Western blots demonstrated that both the membranous and the aqueous fractions of mitochondria contain GST‐α and GST‐μ isoforms, whereas GST‐π was absent.Conclusions HNE detoxification by mitochondrial GST is compromised by short‐term ethanol consumption, which may contribute to elevated mitochondrial HNE content and hence its toxicity in the ethanol‐exposed liver.
Effects of Ethanol and Transforming Growth Factor β (TGFβ) on Neuronal Proliferation and nCAM Expression
Authors: Miller Michael W. , Luo Jia 
Published: April 2006

Background Developmental events targeted by ethanol are cell proliferation, neuronal migration, and neurite outgrowth; the latter processes being mediated by neural cell adhesion molecule (nCAM). TGFβ1 affects all three of these events. Therefore, the effects of ethanol on transforming growth factor (TGF) β1 mediated activities in neocortical neurons in vitro were examined.Methods Primary cultures of cortical neurons were obtained from 16‐day‐old fetuses and were treated with TGFβ1 (0 or 10 ng/ml) and ethanol (0 or 400 mg/dl) for 48 hr. The effects of these substances on cell numbers, [3H]thymidine incorporation, and the expression of nCAM were determined.Results Both cell growth (the change in cell numbers over time) and cell proliferation were inhibited by TGFβ1 and ethanol. The action of these two anti‐mitogenic factors was additive. In contrast, TGFβ1 also promoted the expression of three isoforms of nCAM. Likewise, ethanol also up‐regulated nCAM expression. On the other hand, ethanol blocked TGFβ1‐mediated nCAM expression, particularly of the 120 and 180 kDa isoforms.Conclusions TGFβ ligands inhibit neuronal proliferation and stimulate the expression of cell adhesion proteins that promote the movement of postmitotic neurons and process outgrowth. Ethanol alters these phenomena as well. Thus, in neurons, as in astrocytes, TGFβ1 and ethanol may interact.