bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Factors for Alcohol Dependence: A Questionnaire Survey
Authors: Poikolainen Kari
Published: May 2006

Several factors, known to associate with alcoholism, have not been studied together earlier as determinants of alcohol dependence, and taking into account possible interactions. A representative sample of 302 male and 312 female Finns, aged 19 to 81 years, answered a computerized questionnaire in January 1996. The diagnosis of alcohol dependence was based on the ICD‐10 criteria. There were 66 (10.8%) subjects with current (past 12‐month) ICD‐10 alcohol dependence. After adjusting for other potential correlates in logistic regression analysis, alcohol dependence was more common among subjects high on both asocial behavior and on thinking that his or her behavior is determined mainly by chance or by other people (external control) than among the rest [odds ratio (OR) 4.4; 95% confidence interval (95% Cl) 1.8–10.91. Likewise, alcohol dependence was more common among subjects who recalled that they were highly stimulated when intoxicated by alcohol (OR 3.4; 95% CI 1.9–6.0). High predisposition to anxiety associated strongly with alcohol dependence among males (OR 13.8; 95% CI 4.4–43.1), but not among females (OR 25; 95% CI 0.7–9.1). Several of the aforementioned correlates may be modifiable risk factors for alcohol dependence.
Drug and Alcohol Use Among Injured Motor Vehicle Drivers in Sweden: Prevalence, Driver, Crash, and Injury Characteristics
Authors: Sjögren Harmeet , Björnstig Utf , Eriksson Anders , Öhman Ulla , Solarz Artur
Published: May 2006

Injured motor vehicle drivers who were hospitalized (Umeå: n= 130) and fatally injured drivers who were autopsied (Umeå, Northem Sweden: n= 111; Gothenburg, Westem Sweden: n= 136) from May 1991 through December 1993 were tested for alcohol and for both licit and illicit drugs. Nineteen percent of the Umeå‐hospitalized drivers (UHDs), 26% of the Umeå fatally injured drivers (UFDs), and 21% of the Gothenburg fatally injured drivers (GFDs) tested positive for drugs and/or alcohol. Ten percent of the UHDs, 8% of the UFDs, and 6% of the GFDs tested positive for drugs. Almost 5% of the UHDs, had illicit drugs, and 6% had licit drugs. Only 3% of the GFDs and none of the UFDs had illicit drugs. Bemzodiazepines, followed by opiates, tetrahydrocannabinol, and amphetamine were the most common drugs detected. Twelve percent of the UHDs, 24% of the UFDs, and 17% of the GFDs tested positive for alcohol. Two percent of the UHDs, 6% of the UFDs, and 2% of the GFDs had a combination of drugs and alcohol.
Differential Expression of Mitochondria1 NADH Dehydrogenase in Ethanol‐Treated Rat Brain: Revealed by Differential Display
Authors: Chen W. , Hardy P. , Wilce P. A.
Published: May 2006

The technique of polymerase chain reaction (PCR) differential display was used to detect alterations in gene expression after chronic alcohol administration. Male Wistar rats were treated with ethanol vapor for 14 days. The cDNA generated from mRNA isolated from the hippocampi of ethanol‐treated and control animals was compared by PCR differential display. A differentially expressed cDNA fragment was used to screen mRNA samples by Northern analysis. The level of a mRNA was significantly elevated (× 2.5) in the hippocampus, but not the cortex of alcohol‐treated rats up to 48 hr after withdrawal. Sequence analysis of the cDNA fragment revealed an almost perfect homology to rat mitochondrial NADH dehydrogenase subunit 4 mRNA. The selective induction of this mRNA in alcohol‐treated rat brain areas suggests altered metabolic processes and possible dysfunction of the mitochondria. The technique of PCR differential display may prove useful in further analysis of gene expression during alcohol dependence and withdrawal.
Retinoic Acid Reverses Ethanol‐Induced Cardiovascular Abnormalities in Quail Embryos
Authors: Twal Waleed O. , Zile Maija H.
Published: May 2006

The effect of ethanol on early avian cardiovascular development was investigated in stage 8 quail embryos grown in culture for 24 hr. When the culture medium contained 1 % ethanol, 50% of the embryos developed abnormalities of the cardiovascular system, some of which resembled vitamin A deficiency. Only 15% of the embryos grown in control media developed abnormalities attributed to the manipulation of the embryo. When all‐trans‐retinoic acid, the active form of vitamin A, was added at 10−8 M to the ethanol‐containing medium, the cardiovascular development was similar to that of untreated controls. Inclusion of 4‐methylpyrarole and citral, enzyme inhibitors for the conversion of retinol to retinoic acid, produced cardiovascular abnormalities in embryos similar to those observed in vitamin A deficiency. These abnormalities were partially prevented by the presence of 10−8 M all‐trans‐retinoic acid in the medium. lmmunohistochemical studies using antibodies specific for the heart muscle myosin heavy chain (MF‐20) and quail endothelial cells (QH‐1) revealed that looping of the heart of ethanol‐treated embryos was prevented, and the embryonal circulation had no or minimal vascular connections to the extraembryonic circulation. Our studies provide indirect evidence that ethanol is producing vitamin A deficiency during embryonic cardiovascular development and that these effects are specifically prevented by the presence of retinoic acid. These findings may explain some of the symptoms of fetal alcohol syndrome.
Effects of Maternal Ethanol Consumption and Buspirone Treatment on 5‐HT1A and 5‐HT2A Receptors in Offspring
Authors: Kim Jung‐Ae , Gillespie Roberta A. , Druse Mary J.
Published: May 2006

In utero ethanol exposure results in a decreased concentration of serotonin (5‐HT) in brain regions containing the cell bodies of 5‐HT neurons and their cortical projections. The concentration of 5‐HT reuptake sites is also reduced in several brain areas. The present study extended prior work by evaluating the effects of chronic maternal ethanol consumption and maternal buspirone treatment on 5‐HT1A and 5‐HT2A receptors in multiple brain areas of offspring. Receptors were quantitated early in postnatal development and at an age when the 5‐HT networks are normally well‐established. Because fetal 5‐HT functions as an essential neurotrophic factor, these studies also determined whether treatment of pregnant rats with buspirone, a 5‐HT1A agonist, could overcome the effects of the fetal 5‐HT deficit and prevent ethanol‐associated receptor abnormalities. The results demonstrated that in utero ethanol exposure significantly alters the binding of 0.1 nM [3H]‐8‐hydroxy‐dipropylaminotetralin to 5‐HT1A receptors in developing animals. Ethanol impaired the development of 5‐HT1A receptors in the frontal cortex, parietal cortex, and lateral septum; these receptors did not undergo the normal developmental increase between postnatal days 19 and 35. The dentate gyms was also sensitive to the effects of in utero ethanol exposure. 5‐HT1A receptors were increased in this region at 19 days. Maternal buspirone treatment prevented the ethanol‐associated abnormalities in 5‐HT1A receptors in the dentate gyms, frontal cortex, and lateral septum. Neither maternal ethanol consumption nor buspirone treatment altered the binding of 2 nM [3H]ketanserin to 5‐HT2A receptors in the ventral dentate gyrus, dorsal raphe, parietal and frontal cortexes, striatum, substantia nigra, or nucleus accumbens.
Hormonal (ACTH, Cortisol, β‐Endorphin, and Met‐Enkephalin) and Cardiovascular Responses to Hyperthermic Stress in Chronic Alcoholics
Authors: Vescovi P. P. , DiGennaro C. , Coiro V.
Published: May 2006

Chronic alcohol drinking causes profound alterations in hypothalamic‐pituitary function. In the present study, endocrine [corticotropin (ACTH), β‐endorphin, cortisol, and met‐enkephalin] and cardiovascular (blood pressure) changes in response to hyperthermic stress (sauna at 90°C for 30 min) were evaluated in 25 normal men (25 to 50 years old) and in 48 male alcoholic subjects (34 to 56 years old) after 5 weeks of abstinence. Significantly lower increments in systolic blood pressure were observed in alcoholics than in control subjects. Furthermore, alcoholics showed lower ACTH, β‐endorphin, and cortisol increments in response to sauna than normal controls. In contrast, sauna‐induced hyperthermia did not change significantly the circulating met‐enkephalin levels in either normal controls or chronic alcoholics. These data suggest that an impairment in the adaptive response to stress affects alcoholic men even after a few weeks of abstinence from alcohol.
Ultrasonic Vocalization Behavior Differs Between Lines of Ethanol‐Preferring and Nonpreferring Rats
Authors: Knapp Darin J. , Kampov‐Polevoy Alexey B. , Overstreet David H. , Breese George R. , Rezvani Amir H.
Published: May 2006

To further understand the relationship between emotional state and alcohol intake in rats, the tendency to emit ultrasonic vocalizations in response to an aversive, but nonpainful, air puff stimulus was tested in several rat lines. Included in this group were Maudsley Reactive (MR) and Non‐Reactive (MNR) rats, and several lines of rats with either high ethanol preference or a low ethanol preference: Preferring, (P), Alko‐Alcohol (AA), and Fawn‐Hooded (FH) animals; and Non‐Preferring (NP), Alko‐Non‐Alcohol (ANA), and Flinders Resistant Line (FRL). MR rats emitted fewer ultrasonic vocalizations (USVs) and showed less preference for ethanol than did MNR animals. An overall analysis that included the P, NP, FH, FRL, AA, and ANA groups demonstrated a significant negative correlation between the total number of USVs emitted and ethanol consumption. NP, FRL, and especially ANA rats (low ethanol‐preferring) emitted the most USVs—to an extent similar to that typically found for normal rats. The duration of vocalizing was higher only in the NP and the FRL rats the relative to their P and FH comparison groups, respectively. In the ethanol‐preferring and nonpreferring lines, the numbers of USVs emitted correlated positively with the duration of vocalizing, but not with the latency to vocalize, which in turn did not correlate strongly with ethanol intake. The latency to vocalize did not correlate significantly with ethanol intake across all drinking lines or MR or MNR rats, but was found to be higher in FH and AA rats relative to their nondrinking comparison groups. These associations suggest that the relationship between emotional state and ethanol drinking is complex and cannot be attributed to a simple elevated state of anxiety or emotionality. Further examination of the central nervous system mechanisms mediating the difference in USVs between paired lines of ethanol—preferring and nonpreferring rats may identify neurochemical factors that predict ethanol preference.
Ethanol Inhibits Inducible Nitric Oxide Synthese Transcription and Post‐Transcriptional Processes in Vivo
Authors: Zhao Xinfang , Jie Oyang , Li Hua , Xie Jianming , Giles Thomas D. , Greenberg Stan S.
Published: May 2006

The effects of ethanol (ETOH) on post‐transcriptional regulation of inducible nitric oxide synthase (iNOS) in vivo has not been demonstrated. We examined the effect of ETOH on iNOS mRNA, protein, and the production of the nitrate and nitrite anion (RNI) in rat lung alveolar macrophages (AM) in vivo when stimulated by lipopolysaccharide (LPS) and dibutyryl cyclic AMP (DB‐cAMP). Sprague‐Dawley rats (225‐250 g) (n= 5‐7/gp) were given intratracheal LPS (0.6 mg/kg) or DB‐cAMP (0.1 and 1 mg/kg) 30 min after ETOH (4 mg/kg, intraperitoneally (ip)) or phosphate‐buffered sterile saline (PBS) (5 ml/kg, ip) or pyrrolidine dithiocarbamate (PDTC 10 mg/kg, intratracheally) or 15 min after diethyl dithiocarbamate (DETC) (5 mg/kg, intratracheally). At selected times after administration of LPS or DB‐cAMP, the animals were anesthetized, the lungs with the heart attached were removed and the lungs subjected to bronchoalveolar lavage (BAL). The BAL fluid was assayed for tumor necrosis factor alpha (TNFα) and RNI. The BAL fluid AM were isolated and analyzed for iNOS mRNA and protein with competitor‐equalized polymerase chain reaction (PCR) and Western blots, respectively. The ex vivo incubates of AM were assayed for RNI and TNFα. LPS and DB‐cAMP each increased iNOS mRNA and protein in AM and RNI in the BAL fluid and ex vivo incubates of AM. However, the peak of the increase of iNOS mRNA occurred at 2 hr for DB‐cAMP and 4 to 6 hr for LPS. Only LPS increased the concentrations of TNFα in BAL fluid and ex vivo incubates of AM. ETOH attenuated LPS‐mediated up‐regulation of iNOS mRNA and TNFα and iNOS protein and RNI produced by the AM. In contrast, pretreatment of rats with ETOH did not affect DB‐cAMP‐mediated increases of iNOS mRNA in AM at any time but suppressed the amount of iNOS protein and RNI produced in DB‐cAMP‐stimulated AM. DETC, but not PDTC, attenuated LPS‐mediated up‐regulation of iNOS mRNA without effects on that produced by DB‐cAMP. Since ETOH and DETC, but not PDTC, suppressed LPS‐mediated but not DB‐cAMP‐mediated transcription of iNOS, we conclude that two distinct pathways exist for induction of iNOS mRNA by these agonists. ETOH and DETC may inhibit the LPS‐mediated activation pathway by acting as antioxidants. Also, since ETOH inhibited DB‐cAMP‐mediated increases in iNOS protein without affecting iNOS mRNA ETOH also acts at a post‐transcriptional or translational site to inhibit iNOS protein in rat AM in vivo.
The Nexus between Alcohol and Violent Crime
Authors: Zhang Lening , Wieczorek William F. , Welte John W.
Published: May 2006

The present study examines the nexus between alcohol and violent crime by specifying alcohol as a moderating variable that may interact with other major causes of violent crime. Four major causes of violent crime at the individual level are identified: deviant motives or attitudes, aggression and hostility, impulsivity, and problem‐solving ability. Analyses are conducted at two levels of aggravated assault: prevalence of assault and frequency of assault. At the level of prevalence of assault, data indicate that the usual drinking pattern does not constitute an independent cause, but has significant interactions with two of the major causes: deviant attitudes and aggression and hostility. However, in the analysis of the frequency of assault, the findings indicate a pattern that both usual drinking pattern and drinking before offending have independent explanatory power for aggravated assault, but no interactions were found. These findings suggest that alcohol may have different roles in explaining different levels of violent offending.
Comparison of Screening Instruments for Alcohol Problems Between Black and White Emergency Room Patients from Two Regions of the Country
Authors: Cherpitel Cheryl J.
Published: May 2006

A number of brief screening instruments to identify alcohol dependence exist, but the validity of these instruments across ethnic groups or regions of the country is not well established. The sensitivity and specificity of a number of standard screening instruments (CAGE, brief MAST, AUDIT, TWEAK, and RAPS), as well as other measures (History of Trauma Scale, breathalyzer reading, self‐reported drinking before the event, and consuming five or more drinks at a sitting at least monthly) are compared against ICD‐10 and DSM‐IV criteria for alcohol dependence between probability samples of Black and White emergency room patients in Santa Clara County, CA (n= 716) and in Jackson, MS (n= 1330). Variability in the sensitivity of screening instruments among current drinkers was found to be greater between samples for both Blacks and Whites, than for Blacks compared with Whites within the same sample. The AUDIT, TWEAK, and RAPS seemed to perform well by gender and injury status for both Blacks and Whites in the two samples, and no significant differences were found in the performance of these instruments across sample sites. To evaluate the influence of regional differences in alcohol dependence on differences found in the performance of screening instruments, using logistic regression with the simultaneous entry of demographic variables (age, gender, ethnicity, injury status, and site) and drinking variables (breathalyzer reading, serf‐reported drinking before the event, and drinking five or more drinks at a sitting at least monthly) to predict alcohol dependence in a merged sample of these patients (Jackson vs. Santa Clara) site was not found to be significant Data suggest that, whereas region of the country may not be important in predicting alcohol dependence in emergency room populations, regional differences in the performance of screening instruments for alcohol dependence may exist, even when ethnicity is taken into account Given distinct regional differences in drinking patterns and problems in the U.S., further research on commonly used screening instruments is needed to determine those screeners most efficient for identifying problem drinking.
Selective Inhibition of Alcohol Intake in Diverse Alcohol‐Preferring Rat Strains by the 5‐HT2A Antagonists Amperozide and FG 5974
Authors: Overstreet David H. , McArthur Robert A. , Rezvani Amir H. , Post Claes
Published: May 2006

The present studies sought to elucidate the role of 5‐HT2A receptor antagonists in suppressing alcohol intake by comparing the effects of amperozide and FG 5974 on alcohol, food, and water intake in strains of alcohol‐preferring rats: P, Alko Alcohol (AA), and Fawn‐Hooded (FH). Both amperozide and FG 5974 have 5‐HT2A receptor antagonist properties, but FG 5974 also shows presynaptic 5‐HT1A receptor agonist activity. After establishment of stable baselines for intake measures in a two‐bottle continuous access paradigm, rats (n= 10) were injected with 1 of 5 doses (0, 1.0, 2.5, 5.0, and 10.0 mg/kg, sc) of amperozide or FG 5974 at weekly intervals. Amperozide dose‐dependently reduced alcohol intake, total fluid intake, and alcohol preference in all three strains under continuous access conditions, whereas FG 5974 was less effective. Food intake was also suppressed by amperozide at higher doses, whereas it was increased by FG 5974. Amperozide also dose‐dependently reduced alcohol intake when it was available for only 1 hr/day, but FG 5974 tended to increase it. After oral administration, amperozide was also more effective than FG 5974 in reducing alcohol intake. Despite these differences in efficacy in suppressing alcohol intake, both compounds produced taste aversion to a novel saccharin solution. These complex findings suggest that biochemical properties other than 5‐HT2A receptor antagonism (e.g., 5‐HT1A receptor agonism) may be involved in the effects of amperozide and FG 5974 on alcohol intake and other consummatory behaviors.
Effects of Acetaldehyde on Brush Border Enzyme Activities in Human Colon Adenocarcinoma Cell Line Caco‐2
Authors: Koivisto Tiina , Salaspuro Mikko
Published: May 2006

The treatment of Caco‐2 cells, a human colon adenocarcinoma cell line that closely resembles normal human small intestinal epithelial cells, with acetaldehyde resulted in significantly decreased activities of brush border enzymes sucrase, maltase, lactase, and γ‐glutamyl‐transferase; alkaline phosphatase activity was not affected. In the case of sucrase and maltase, the activities were also decreased by a combination of acetaldehyde and ethanol, although ethanol alone markedly increased them. The possibility that intraintestinal acetaldehyde, formed by intestinal microbes, might play a role in some small intestinal enzyme deficiencies observed earlier in alcoholics should therefore be considered. The mechanism by which acetaldehyde alters these enzyme activities remains unclear. The observation that acetaldehyde also disturbed cell polarization, an initial step in the process of differentiation in Caco‐2 cells, indicates that acetaldehyde might decrease these enzyme activities by interfering with cell differentiation. Because ethanol and acetaldehyde metabolizing enzymes have not been previously studied from Caco‐2 cells, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities were also measured from these cells, and their ALDH isoenzyme pattern was characterized. Like many cancerous cell lines, Caco‐2 cells were found to express no ADH. They, however, possessed ALDH activity that was comparable with normal colonic mucosal activity and also expressed the same ALDH classes (ALDHs 1 to 3) than normal human colonie mucosa.
Cytochrome P‐4502E1‐Dependent Formation of Trifluoroacetyl Adducts from Halothane by Transduced HepG2 Cells
Authors: Feierman Dennis E. , Melnikov Zoya
Published: May 2006

E‐9 cells, a HepG2 cell line that has the alcohol‐inducible human cytochrome P‐4502E1 (CYP2E1) cloned into its genome, was tested for its ability to produce trifluoroacetyl (TFA) adducts from the metabolism of halothane. The metabolism of halothane results in the production of TFA halide that can readily react with cellular proteins to form TFA adducts, which can be detected by antibodies directed against them. E‐9 cells formed TFA adducts when incubated with halothane. The major consistent bands that were detected were of molecular weights of ˜50, 78, and 100 kDa. The formation of these adducts was dependent on halothane concentration and time of incubation with halothane. MV‐5 cells, the control cell line that has the viral vector without the P‐450, did not produce any adducts. Inhibitors of CYP2E1 function, such as 4‐methylpyrazole, inhibited adduct formation. Furthermore, phorbol esters, which have been shown to increase the CYP2E1 level in this cell line, increased TFA adduct formation. This HepG2 cell line may be of value in studying the metabolism and toxicity of halothane in a human cell culture model.
Alcoholism and Carcinoma Change the Intracellular PH and Activate Platelet Na+/H+‐Exchange in Men
Authors: Spies Claudia D. , Spies Klaus‐Peter , Zinke Silke , Runkel Norbert , Berger Gerd , Marks Christian , Helling Kai , Blum Susanne , Müller Christian , Rommelspacher Hans , Schaffartzik Walter
Published: May 2006

The occurrence of carcinoma in chronic alcoholics exceeds that of the general population. Cytoplasmic alkalinization, due to the influence of different factors on the transmembrane Na+/H+ exchange (NHE), has been put forward as a triggering event in cell growth and division. In accordance with these findings, the carcinogenic potential of NHE deficient cell types is reported to be diminished. The aim of this study was to investigate whether the intracellular pH and the NHE activity is altered in chronic alcoholics. Seventy‐two Caucasian males were assigned to one of four groups: non‐alcoholics without carcinoma, chronic alcoholics without carcinoma, non‐alcoholics with carcinoma and chronic alcoholics with carcinoma. Alcoholism was diagnosed according to DSM‐III‐R. The groups did not differ in relation to basic patient characteristics, such as age and blood pressure. Intracellular calcium, pH and NHE in platelets were determined by spectrofluorometry before and after thrombin stimulation. In chronic alcoholics with carcinoma, the intracellular pH was significantly more alkaline and the NHE activity was elevated. In contrast, a decrease in intracellular pH associated with an increased activity of NHE and a more acidic set point was found in chronic alcoholics without carcinoma. Basal and thrombin stimulated intracellular Ca2+ did not differ between groups except in chronic alcoholics with carcinoma in whom a thrombin‐induced increase of Ca2+ due to liberation of Ca2+ from intracellular stores was demonstrated. In chronic alcoholics with carcinoma, cytoplasmic alkalinization was observed and this may be an indication of an increase in cell proliferation. The possibility that the increased incidence of carcinomas in chronic alcoholics is related to the increased activity of NHE and whether this may be prevented by NHE inhibitors requires further investigation.
II: The Effects of Recombinant Human Insulin‐Like Growth Factor‐1 on Immunological Recovery in the Malnourished Alcoholic Rat
Authors: Mendenhall Charles L , Roselle Gary A. , Grossman Charles J. , Gartside Peter
Published: May 2006

Background/aims: Immunological abnormalities are frequently observed in alcoholics with severe liver disease and are typically in association with immune abnormalities. Concomitantly, serum levels of insulin‐like growth factor‐1 (IGF‐1) are frequently very low in these patients. Because IGF‐1 is known to modulate both nutrition and immune status, the present study was undertaken to evaluate an in vivo rat model of alcoholism and malnutrition, the possibility of a therapeutic application for IGF‐1. Methods: Controlled injury was induced by 14 days of calorie restriction and alcohol feeding that resulted in a 9% loss of body mass. Changes were compared with normal unrestricted control rats that gained 28% above their pre‐treatment body mass during the same period. Immunological impairment was assessed using thymus and spleen mass, cellularity and spleen T‐lymphocyte function. Recovery was evaluated after 28 days of treatment using various combinations of: (1) high calorie intake, (2) cessation from alcohol feeding, and (3) IGF‐1. Results: The thymus was most severely affected, losing 52.3% of its mass and 55.7% of its cellularity. The spleen was diminished, losing 31.2% of its mass and 41.9% of its cellularity. All of the spleen T‐lymphocyte subsets were diminished, with CD5 affected the least (37.1 %) and CD8 affected the most severely (51.7%). During recovery, only the group treated with high calorie intake, no alcohol intake, and IGF‐1 (group 8) had complete restoration of all immunological parameters, including a recovery of T‐lymphocyte function. Continuous consumption of alcohol, even in the presence of high calories and IGF‐1, produced an incomplete recovery. Conclusions: Cessation of alcohol coupled with high calorie nutrition and IGF‐1 treatment produced an accelerated improvement in host immunity. These animal studies suggest that IGF‐1 is efficacious for this condition and supports the need for additional clinical studies.
Oral and Dental Health in Alcohol Misusing Patients
Authors: Harris C. , Warnakulasuriya K. A. A. S. , Gelbier S. , Johnson N. W. , Peters T. J.
Published: May 2006

Dental and oral health and their relationship to nutritional status among a group of alcohol misusers (n= 107) from south London is reported. The Alcohol Use Disorders Identification Test (AUDIT) questionnaire was validated as an accurate and reliable screening questionnaire for use in alcohol misuse detection by a dentist. Half of the study population consumed >200 units of alcohol/week, and 80% were heavy smokers. A high incidence of tooth wear and trauma to the dentition was recorded. Eight subjects had oral mucosal lesions, including two previously treated carcinomas. The dental health in alcoholics overall was not compromised, but nutritional impairment (body mass index and reduced midarm muscle circumference) was associated with periodontal lesions. Oral mucosal health of alcoholics is of concern, particularly in heavy smokers. The interrelationships between dental‐oral health and alcohol‐tobacco usage have implications for preventative counseling in this patient group.
Clinical Significance of Hepatitis GB Virus C Infection in Alcoholic Liver Disease
Authors: Tsutsumi Mikihiro , Sawada Makoto , Takase Shujiro , Chen Wun‐Bil , Ueshima Yasuhiro , Tsuchishima Mutsumi , Shimanaka Koshi , Itoh Tohru , Kawahara Hiromu
Published: May 2006

Recently, hepatitis GB virus C (HGBV‐C) has been recovered from patients with non‐A‐E hepatitis. However, it has been unclear whether HGBV‐C may be related to the development of alcoholic liver disease (ALD) or not. In this study, we determined HGBV‐C RNA in sera from alcoholic patients without markers for hepatitis C and B viruses to evaluate the role of HGBV‐C in ALD. Serum samples were obtained from 68 patients with ALD and 40 nonalcoholic patients with chronic type C liver disease. HGBV‐C RNA was detected in only 3 of 68 (4.4%) patients with ALD, in 2 of 27 patients with hepatic fibrosis, and in 1 of 5 patients with chronic hepatitis. There was no HGBV‐C RNA in sera from patients with fatty liver, alcoholic hepatitis, or cirrhosis. Serum levels of AST, ALT, and γ‐glutamyltranspeptidase in alcoholic patients with, as well as without, HGBV‐C RNA decreased to normal levels after abstinence. In addition, an inflammatory change was not observed in liver biopsy specimens obtained from two HGBV‐C‐positive patients with alcoholic hepatic fibrosis. Our results clearly suggest that the prevalence of HGBV‐C infection in patients with ALD is rare and that HGBV‐C may not play an important role in the development of liver disease in alcoholics.
Axis I and Axis II Comorbidity in Alcohol Dependence and the Two Types of Alcoholism
Authors: Driessen Martin , Veltrup Clemens , Wetterling Tilman , John Ulrich , Dilling Horst
Published: May 2006

Background: Although high prevalence rates of psychiatric comorbidity were reported in alcoholism, there is a lack of studies covering the whole spectrum of DSM Axes I and II disorders. The relation of comorbid psychopathology and Cloninger's and Babor's types of alcoholism still remained unclear. Methods: Psychiatric comorbidity in 250 hospitalized alcohol‐dependent patients without additional substance‐related disorders was assessed by the Composite International Diagnostic Interview and the International Personality Disorder Examination. Information about the course and severity of alcoholism was obtained from several sources. Results: Additional Axis I disorders only were found in 24.0%, Axis II disorders only in 16.4%, and concurrent Axis I and Axis II disorders in 17.2% (total comorbidity rate: 57.6%). Two clusters of alcohol dependence were found that substantially overlap with Cloninger's and Babor's types of alcoholism. The majority of type A subjects were found to be either not comorbid at all, or to be Axis I comorbid only. Type B, on the other hand, was preferably associated with personality disorders (mainly Clusters A and B) and dimensional scores of personality pathology (schizoid, schizotypal, all Cluster B, and passive‐aggressive). Conclusions: The entire spectrum of personality pathology should be assessed in the comorbidity research of alcoholism. The two types of alcoholism differ on a variety of alcohol‐related and comorbid personality characteristics, but further research is needed to clarify the underlying psychological and biological associations.
Relevance of Both Daily Hassles and the ALDH2 Genotype to Problem Drinking among Japanese Male Workers
Authors: Takeshita Tatsuya , Maruyama Soichiro , Morimoto Kanehisa
Published: May 2006

The effects of genetic polymorphisms in the ALDH2 and ADH2 genes and stress levels, as assessed by the daily hassles scale on the prevalence of problem drinkers, were investigated in males in a Japanese occupational population. The frequency of problem drinkers was estimated by the Kurihama Alcoholism Screening Test (KAST). The prevalence of those with a high KAST score (≥0.0) was significantly higher in ALDH2*1/*1 (18.4%) than in ALDH2*1/*2 (4.8%). Multiple logistic regression analysis revealed significant contributions by levels of alcohol consumption, the ALDH2 genotype, and daily hassles to the prevalence of those with a high KAST score. When we analyzed the data for each ALDH2 genotype, heavier alcohol consumption (≥28.8 ml/day), older age (≥40 years old), and very high daily hassles levels (≥20) significantly increased the prevalence of problem drinkers in ALDH2*1/*1. On the contrary, no variables other than heavier alcohol consumption influenced the prevalence in ALDH2*1/*2. In summary, the present study revealed significant contributions of both daily hassles and the ALDH2 genotype to the increase of problem drinkers in an occupational population. Health promotion activities to prevent from alcohol dependence should focus on ALDH2*1/*1, especially those of middle age, and should include stress management as a part of their activities.
Ethanol‐Induced Neural Crest Apoptosis Is Coincident with Their Endogenous Death, But Is Mechanistically Distinct
Authors: Cartwright Martina M. , Tessmer Laura L. , Smith Susan M.
Published: May 2006

The ability of both acute and chronic ethanol exposures to elicit cell death within specific embryonic and adult tissues is believed to partly underlie ethanol's pathogenicity; however, the mechanism underlying this cell death is unknown. This study partially characterized the mechanism of ethanol‐induced neural crest cell death in a chick embryo model of fetal alcohol syndrome. In situ DNA end‐labeling demonstrated this cell death was apoptotic and occurred at embryonic ethanol levels as low as 42 mM. Regardless of the initial exposure time, this apoptosis always appeared at a distinct developmental time point simultaneous with the normal deletion of a cranial neural crest subset. This suggested that ethanol might act through aberrant activation of the endogenous death pathway; however, ethanol exposure failed to induce two components of this pathway, the homeotic transcription factor msx‐2 and the growth factor bone morphogenetic protein 4. Both endogenous and ethanol‐induced death were blocked by local application of an interleukin‐1 β converting enzyme/CED‐3 protease (caspase) inhibitor, showing that the two paths converge mechanistically and suggesting the potential to prevent this aspect of ethanol's teratogenicity. Ethanol exposure did not significantly alter cell proliferation within neural crest‐populated regions, suggesting that susceptibility to ethanol‐induced death did not involve exit from the cell cycle. Apoptotic deletion of cranial neural crest could partially explain the craniofacial deficits characteristic of the fetal alcohol syndrome.
Decreased Tumor Necrosis Factor‐α and Interleukin‐1α Production from Intrahepatic Mononuclear Cells in Chronic Ethanol Consumption and Upregulation by Endotoxin
Authors: Batey R. , Cao Q. , Madsen G. , Pang G. , Russell A. , Clancy R.
Published: May 2006

The relationship between the changes in liver pathology and the production of interleukin (IL)‐1α, IL‐6, and tumor necrosis factor‐α (TNF‐α) by intrahepatic mononuclear cells was studied in rats fed alcohol and subsequently exposed to lipopolysaccharide (LPS). Rats were fed 40% ethanol in drinking water, whereas control rats were provided with a chow diet with isocaloric or 2% sucrose drinking solutions for up to 20 weeks. Decreased IL‐1α and TNF‐α production in 24‐hr culture supernatants of mononuclear cells isolated from liver perfusate was detected while IL‐6 remained unchanged over 20 weeks. When animals were injected with LPS (1.0 μg/kg body weight), there was a 5‐fold rise in ALT levels in the ethanol‐fed group, but not in control groups. Increased IL‐6 and TNF‐α levels in the serum and supernatant of cultured intrahepatic mononuclear cells stimulated with or without LPS or concanavalin A was observed. There was a correlation between levels of ALT and TNF‐α, but not IL‐6. T cells and Kupffer cells were the major source of TNF‐α in culture supernatants of hepatic perfusate mononuclear cells from ethanol‐consuming rats injected LPS. In addition, pathological liver injury was evident, which suggests a pathogenic role for TNF‐α in alcohol‐induced liver disease.
Effect of Ethanol on Intracellular Vesicular Transport from Golgi to the Apical Cell Membrane: Role of Phosphatidylinositol 3‐Kinase and Phospholipase A2 in Golgi Transport Vesicles Association and Fusion with the Apical Membrane
Authors: Slomiany Amalia , Nowak Pawel , Piotrowski Elizabeth , Slomiany Bronislaw L.
Published: May 2006

The study of ethanol effects on intracellular transport and membrane biogenesis in rat hepatocytes revealed that, during synthesis of transport vesicles, the cytosolic phosphatidylinositol 3‐kinase incorporated into the membrane of Golgi transport vesicles and a portion of the vesicular phosphatidylinositol was phosphorylated to phosphatidylinositol 3‐phosphate. Association of the enzyme with Golgi transport vesicles and the transport to the apical portion of the cell membrane was not affected by 0 to 120 mM ethanol, but was dependent on the presence of the p85 subunit of the phosphatidylinositol 3‐kinase. In the presence of ATP‐enriched cytosol and calcium ions, association of Golgi transport vesicles with the apical membrane was followed by phospholipase A2‐specif ic hydrolysis of phosphatidylinositol 3‐phosphate and incorporation of the transport vesicle membrane into the apical membrane. Association of Golgi transport vesicles with apical membranes was not affected by preincubation of the cell membrane or Golgi transport vesicles with 0 to 120 mM ethanol, but was inhibited when the p85 phosphatidylinositol 3‐kinase was incorporated into the membrane before incubation with Golgi transport vesicles. The fusion of Golgi transport vesicles with the apical membrane and generation of lysophosphatidylinositol 3‐phosphate and arachidonate was inhibited with EGTA or after depletion of ATP from cytosol. Results of these studies provide evidence that phosphatidylinositol 3‐kinase and phospholipase Aj activities are crucial for the final step of exocytotic transport. The process consists of two stages. First, the p85 subunit of phosphatidylinositol 3‐kinase is involved in the specific association of the vesicle with membrane receptor, and that is followed by phospholipase A2‐specific lysophospholipid generation, perturbation of the membranes, and fusion of the transport vesicle membrane with the apical membrane. Addition of ethanol to the in vitro transport system decreased production of Golgi transport vesicles, but had no effect on their association with apical membrane or fusion with the membrane.
Ethanol Exposure Potentiates fosB and junB Expression Induced by Muscarinic Receptor Stimulation in Neuroblastoma SH‐SY5Y Cells
Authors: Ding Wei‐Qun , Fried Ulrik , Larsson Christer , Ailing Christer
Published: May 2006

Muscarinic receptor stimulation and activation of protein kinase C cause an increase in fosB and junB transcripts in human neuroblastoma SH‐SY5Y cells. In this study, the effect of long‐term ethanol exposure on these events was investigated. Carbachol‐stimulated fosB and junB expression was elevated in ethanol‐exposed cells compared with control cells. The potentiation was time‐ and dose‐dependent on ethanol. Preincubation with muscarinic antagonists or protein kinase C inhibitor demonstrated that the carbachol‐stimulated increase in fosB and junB mRNA levels was primarily mediated via M1 receptors and dependent on the activity of protein kinase C in both control and ethanol‐exposed cells. Long‐term ethanol exposure did not influence the expression of fosB and junB induced by activation of protein kinase C with phorbol ester. These results demonstrate that the muscarinic receptor‐stimulated fosB and junB expression is sensitive to ethanol exposure in SH‐SY5Y cells, suggesting that these genes participate in the regulation of neuronal function in response to chronic ethanol treatment.
Free Methionine Supplementation Limits Alcohol‐Induced Liver Damage in Rats
Authors: Parlesak Alexandr , Bode Christiane , Bode J. Christian
Published: May 2006

Alcohol feeding to rats that were submitted to a jejunoileal bypass operation has been shown to result in liver damage being comparable with alcohol‐induced liver disease in man. In the present study, a striking effect of free methionine consumption on histological liver injury, triglyceride accumulation, and energy‐rich nucleoside content in the liver of rats with a jejunoileal bypass is demonstrated. The animals obtained 0, 30, and 120 mg of methionine in the control group and 0,30,120, and 240 mg in the alcohol‐fed group per day and per kilogram of body weight for 12 weeks. Methionine was found to strongly improve the alcohol‐induced histological changes in the liver. Triglyceride content of the liver was found to decrease in a dose‐dependent manner with increasing methionine ingestion (from 255 ± 20.7 to 49.7 ± 6.1 μmol/g of protein in the control group and from 233 ± 17.3 to 42.1 ± 7.2 μmol/g of protein in the alcohol group). Hepatic adenosine triphosphate content increased significantly with higher methionine consumption (13.5 ± 0.8 vs. 26.9 ± 2.8 μmol/g of protein in the control group and 11.9 ± 1.4 vs. 20.5 ± 2.5 μmol/g of protein in the alcohol group), whereas no differences were found in the protein and DNA content of the liver. These results underscore the impairment of the transmethylation/transsulfuration pathway in the development of alcohol‐induced liver diseases.
Effects of Acute and Chronic Doses of Naltrexone on Ethanol Self‐Administration in Rhesus Monkeys
Authors: Boyle A. E. L. , Stewart R. B. , Macenski M. J. , Spiga R. , Johnson B. A. , Meisch R. A.
Published: May 2006

The effects of acute and chronic administration of intramuscular naltrexone (0.1, 0.3, 1.0, and 3.0 mg/kg) on oral ethanol (8%) self‐administration were examined. Naltrexone (1.0 mg/kg) effects on the self‐administration of ethanol concentrations ranging from 0.5 to 8% (w/v) were also investigated. Rhesus monkeys with substantial histories of drug and ethanol drinking served as subjects. During daily 3‐hr sessions, monkeys were presented with ethanol solutions, concurrently available with water, under fixed‐ratio reinforcement schedules. Naltrexone decreased the consumption of ethanol (g/kg). Biphasic temporal effects were observed within sessions. Naltrexone dose‐dependently decreased the number of ethanol deliveries by a maximum of 56% (n= 18; 3 monkeys × 6 sessions) during the first hour of the session. During the second and third hours, however, ethanol intake recovered such that maximum decreases over the 3‐hr session were ∼27% (n= 18), and the mean decrease was 16% (n= 18). Often marked tolerance was observed, such that the effects of acute naltrexone administration were greater than effects after chronic administration. The self‐administration of low ethanol concentrations (≤2% w/v) was increased in several monkeys, by up to 340%, after naltrexone pretreatment. In summary, the effects of naltrexone on ethanol self‐administration, in drug‐ and alcohol‐experienced rhesus monkeys, are not characterized by unitary decreases in measures of ethanol self‐administration. Rather, differential naltrexone effects were a function of experimental parameters, including the dose and number of naltrexone injections, the ethanol concentration, and the time point of measurement.
How Do Physicians Define “Light,”“Moderate,” and “Heavy” Drinking?
Authors: Abel Ernest L. , Kruger Michael L. , Friedl John
Published: May 2006

Although widely used, terms associated with consumption of alcohol–such as “light,”“moderate,” and “heavy”—are unstandardized. Physicians conveying health messages using these terms therefore may impart confusing information to their patients or to other physicians. As an initial attempt to assess if informal standardization exists for these terms, the present study surveyed physicians for their definitions of such terms. Physicians operationally defined “light” drinking as 1.2 drinks/day, “moderate” drinking as 2.2 drinks/ day, and “heavy” drinking as 3.5 drinks/day. Abusive drinking was defined as 5.4 drinks/day. There was considerable agreement for these operational definitions, indicating there is indeed an informal consensus among physicians as to what they mean by these terms. Gender and age did not influence these definitions, but self‐reported drinking on the part of physicians was a factor. We also asked physicians for their opinions regarding the effects of “light,”“moderate,” and “heavy” drinking on health in general and specifically on health‐related implications for pregnant women, and whether they felt their patients shared these beliefs.
Moderate Alcohol Consumption and Estrogen Levels in Postmenopausal Women: A Review
Authors: Purohit Vishnudutt
Published: May 2006

This report reviews the literature to evaluate association between moderate alcohol consumption and estrogen levels in healthy postmenopausal women. Of the eight studies available in literature on postmenopausal women who were not on estrogen therapy, two analyzed urine samples and six analyzed blood samples for estrogen levels. Of the two urine sample studies, only one reported positive association (p < 0.05) between alcohol consumption and estrogen (estrone and estradiol) levels that increased by 16 to 20%. Of the six blood sample studies, only two– one in American women and one in European women–reported significant increases (p < 0.05) in estradiol levels in response to alcohol consumption. In the American women study, estradiol levels increased only with wine and not with beer or whiskey. In the European women study, estradiol levels increased in Danish and Portuguese women, but not in Spanish women. Thus, further studies are required to establish correlation between moderate alcohol consumption and estrogen levels in postmenopausal women. Of the two studies on postmenopausal women who were on estrogen replacement therapy, one administered estradiol through transdermal patch (0.15 mg) and one orally (1 mg/ day). In both studies, blood estradiol levels were measured after administering a single dose of ethanol orally (0.7–0.75 g/kg of body weight). Estradiol levels were increased by 22 and 300% in the transdermal patch and oral studies, respectively. These results suggest that alcohol consumption may increase blood estradiol levels in postmenopausal women who are on estrogen replacement therapy, and this may increase the risk of breast cancer.
Defective Intracellular Processing of Lactase‐Phlorizin Hydrolase Protein in Rats Prenatally Exposed to Ethanol
Authors: Estrada Gemma , Krasinski Stephen D. , Grand Richard J. , López‐Tejero M. Dolores
Published: May 2006

We have previously shown that fetal exposure to ethanol in rats produces both structural and biochemical abnormalities in absorptive enterocytes. Among the indicators of injury are derangements in the expression of lactase‐phlorizin hydrolase (LPH), which is an essential enzyme for the assimilation of milk. In an animal model of fetal alcohol syndrome, unsuckled newborn rats prenatally exposed to maternal ethanol revealed a 10‐ to 15‐fold increase in the number of LPH mRNA molecules per absorptive enterocyte, compared with controls (Estrada et al., Alcohol. Clin. Exp. Res. 20:1662–1668,1996). However, lactase activity per cell was similar in both groups. The aim of this study was to characterize the effect of prenatal exposure to ethanol on the processing of LPH mRNA and protein. RNase protection assays using 3′‐ and 5′‐directed antisense RNA probes revealed that the LPH mRNA from ethanol‐exposed pups is full length. However, metabolic labeling, followed by immunoprecipitation using an anti‐LPH monoclonal antibody, demonstrated a significant alteration in LPH protein processing. Intestinal explants from 21‐day ethanol‐exposed fetuses that were chased 30 min after a [35S]methionine pulse showed greater amounts of newly synthesized LPH precursors (205 and 220 kDa) and low molecular weight degradation products than controls. However, despite the increases in LPH precursor, the amount of 130 kDa mature LPH was similar in ethanol‐exposed and control explants. These data suggest an increase in intracellular degradation of LPH precursor in rats prenatally exposed to ethanol, which occurs before its insertion into the microvillus membrane. Biosynthesis of LPH appears to be upregulated at the transcriptional level, which overcomes the degradation of LPH precursor during processing.