bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Prenatal Ethanol Exposure on Hippocampal Ionotropic‐Quisqualate and Kainate Receptors
Authors: Martin David , Savage Daniel D. , Swartzwelder H. Scott
Published: April 2006

Previous studies from our laboratories have shown that the consumption of moderate quantities of ethanol by rat dams during pregnancy reduces N‐methyl‐d‐aspartate (NMDA) agonist receptor binding and NMDA‐mediated electrophysiological responses in the hippocampal formation of adult offspring. We hypothesized that prenatal ethanol exposure would produce similar effects on receptor number and agonist‐mediated responses of two so‐called “non‐NMDA” subtypes of glutamate receptors, the ionotropic‐quisqualate (RS)‐α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (AMPA)‐sensitive and the kainate‐sensitive receptors. Sprague‐Dawley rats were fed either a liquid diet containing 3.35% ethanol, an isocalorically matched liquid diet, or lab chow ad libitum throughout gestation. No significant differences between offspring from these three groups in the agonist concentration‐response curves for either AMPA‐induced or kainate‐induced depolarization of hippocampal CA1 pyramidal neurons were observed. Furthermore, no significant differences in the density of [3H]‐AMPA or [3H]‐vinylidene kainic acid binding sites in any of the apical dendritic field regions of dorsal or ventral hippocampal formation were observed between the groups. These results indicate that the ionotropic quisqualate and kainate receptors, located in the apical dendritic field regions of the principal hippocampal neurons, are not affected by the same degree of prenatal ethanol exposure, which is known to reduce NMDA receptor binding and function in these same regions.
Effect of Ethanol on Lipoprotein Secretion in Two Human Hepatoma Cell Lines, HepG2 and Hep3B
Authors: Tam Shui‐Pang
Published: April 2006

The two human hepatoma cell lines, HepG2 and Hep3B, have been demonstrated to metabolize ethanol efficiently even in the absence of alcohol dehydrogenase. By using specific metabolic inhibitors, it was found that the microsomal ethanol‐oxidizing system (MEOS) plays a significant role in ethanol metabolism in these two cell lines. There is a strong positive correlation between the rates of ethanol metabolism and the total cytochrome P‐450 levels in the hepatoma cells. The involvement of the cytochrome P‐450 system was further supported by the induction of aniline p‐hydroxylase activity after ethanol treatment. However, the 3‐ to 4‐fold elevation in aniline p‐ hydroxylase activity was not accompanied by an increase in cytochrome P450IIE 1 mRNA level. Exposure of HepG2 and Hep3B cells to ethanol resulted in an increase of accumulation of apoA‐l (15%‐45% over control) in a dose‐dependent manner (from 5 to 50 mM) of ethanol over a 24‐hr period. All other major apolipoproteins which included apo CII, apo CHI and apoE, with the exception of apoB, were not affected by these treatments. At a concentration of ethanol of 25 mM or greater, accumulation of apoB, VLDL and LDL triglyceride were increased by 20% to 25% over the control level. Elevation of HDL cholesterol (40%‐70% over control) was observed when the cells were exposed to an ethanol concentration of ≥10 mM. Metyra‐pone, which inhibited the MEOS, was capable of blocking the induction of apoAl caused by ethanol treatment.
Age and Ethnicity among Hospitalized Alcoholics: A Nationwide Study
Authors: Booth B. M. , Blow F. C. , Cook C. A. L. , Bunn J. Y. , Fortney J. C.
Published: April 2006

Little is known about the broad‐scale demographic characteristics of low income or indigent alcoholics in public hospital systems. The purpose of the study was to examine issues relative to age, race/ethnicity, and marital status for a large group (n= 62,829) of alcoholic men receiving inpatient care in Department of Veterans Affairs (VA) medical centers nationally. Subjects were VA inpatients completing alcoholism treatment (n= 27,562), in brief alcohol detoxification or short intervention (n = 9,322), or hospitalized for primary diagnoses other than alcoholism but with a secondary diagnosis of alcohol dependence syndrome (n= 25,945). Minority alcoholics were significantly younger than Caucasian alcoholics. Hispanic and African‐American men, as well as older alcoholics, were significantly less likely to complete treatment or attend detoxification and more likely to be hospitalized for other primary diagnoses. Native Americans, however, were most likely to complete alcoholism treatment. Results suggest that members of some minority groups and elderly alcoholics seek inpatient care for diagnoses other than alcoholism and that, as a result, such individuals may need targeted interventions to encourage them to seek alcohol‐specific care.
Family History, Alcohol Use and Dependence Symptoms among Young Adults in the United States
Authors: Harford Thomas C. , Parker Douglas A. , Grant Bridget F.
Published: April 2006

Drawing upon data from the National Longitudinal Survey of young adults, this paper examines the effects of family history of alcoholism and current alcohol use by the young adults. A multivariate analysis of the data from the study indicates that there are both main and interaction effects of family history and current alcohol use on dependence symptoms among the young adults.
Circadian Variation in Plasma Homovanillic Acid Level During and After Alcohol Withdrawal in Alcoholic Patients
Authors: Sano Hidenori , Suzuki Yasuo , Ohara Koichi , Yazaki Rie , Ishigaki Tatsuya , Yokoyama Toshito , Ohara Kenshiro
Published: April 2006

Alcohol withdrawal symptoms in alcoholics were objectively evaluated and classified into three groups according to the severity of their symptoms, and circadian variation in their plasma homovanillic acid (HVA) concentrations was determined at three different intervals after cessation of drinking. The subjects studied were 19 male alcoholic patients and five age‐matched healthy male volunteers. Circadian variation in plasma HVA was compared between each patient group and the control group by two‐way ANOVA. In the sympathetic overactivity (SO) group comprising nine patients and in the clouding of sensorium (CS) group comprising five patients, plasma HVA concentrations on the 2nd and 3rd day and on the 6th and 7th day after cessation of drinking were low but recovered almost normal levels on the 21st and 22nd postcessation day. The delirium tremens group (DT) comprising five patients, however, showed significantly higher plasma HVA than the control group except on the 6th and 7th postcessation day. The higher plasma HVA in the DT group indicates that there is some sort of preparatory state whereby dopamine metabolism is involved in the appearance of hallucinations at alcohol withdrawal and can possibly be used as a predictor of otherwise hardly predictable delirium tremens.
DSM‐III‐R and Proposed DSM‐IV Alcohol Abuse and Dependence, United States 1988: A Nosological Comparison
Authors: Grant Bridget F.
Published: April 2006

The purpose of the present study was to compare DSM‐III‐R and the proposed DSM‐IV (options 1 and 2) diagnostic criteria for alcohol abuse and dependence in representative sample of the United States general population. Alcohol abuse and dependence diagnostic categories were contrasted in terms of prevalence and overlap. The prevalences of DSM‐III‐R and DSM‐IV diagnoses of alcohol abuse and dependence combined were remarkably similar. However, disaggregation of abuse and dependence diagnoses showed that there were major discrepancies between the classification systems. Reasons for these discrepancies are discussed in terms of differences in the number of diagnostic criteria and the content of the DSM‐III‐R and DSM‐IV abuse and dependence categories, the requirement for physiological dependence in DSM‐IV classifications, the relationship between the abuse and dependence categories, and the impact of the duration criteria.
Brain Gray and White Matter Volume Loss Accelerates with Aging in Chronic Alcoholics: A Quantitative MRI Study
Authors: Pfefferbaum Adolf , Lim Kelvin O. , Zipursky Robert B. , Mathalon Daniel H. , Rosenbloom Margaret J. , Lane Barton , Ha Chung Nim , Sullivan Edith V.
Published: April 2006

Magnetic resonance imaging (MRI) was used to study in vivo the brains of 49 patients with chronic alcoholism, 3 to 4 weeks postwithdrawal, and 43 normal healthy controls, all right‐handed male veterans between the ages of 23 and 70 years. MRI scans were analyzed using semi‐automated procedure, which allowed the subcortical regions to be segmented into cerebrospinal fluid (CSF) and brain tissue and the cortical regions to be segmented into CSF, gray matter, and white matter. An age regression model was used to examine the effects of alcohol on brain structure, over and above that expected from the normal aging process. The alcoholics exhibited decreased tissue and increased CSF after correcting for aging. In the cortex, there was significant loss of both gray matter and white matter volume. In this sample of alcoholics, no particular cortical region was preferentially affected or spared. Furthermore, brain tissue volume loss increased with advanced age in the alcoholics. In this group of alcoholics there was no relationship between length of illness and age, i.e., the younger alcoholics had as heavy alcohol use histories as did the older alcoholics. Thus, the increased brain tissue loss with advanced age is interpreted as evidence for age‐related increase in brain vulnerability to chronic alcohol abuse.
Prolonged QT Interval in Alcoholic Autonomic Nervous Dysfunction
Authors: Yokoyama Akira , Ishii Hiromasa , Takagi Toshikazu , Hori Shingo , Matsushita Sachio , Onishi Shohei , Katsukawa Fuminori , Takei Izumi , Kato Shinzo , Maruyama Katsuya , Tsuchiya Masaharu
Published: April 2006

QT prolongation on electrocardiography is related to sudden cardiac death and is frequently found in alcoholics. We studied QT prolongation in relation to the function of cardiac autonomic nerves assessed by the coefficient of variation of the R‐R interval (CVRR) in three age‐matched groups of men: 32 alcoholics with autonomic nervous dysfunction (AN), 32 alcoholics without AN, and 32 healthy controls. The QTc, interval and CVRR were measured at rest on the 30th day of abstinence, when electrolyte imbalance had disappeared. Subjects with arrhythmia, conduction abnormality, cardio‐megaly, ischemic heart disease or diabetes mellitus were excluded. A CVRR of less than 80% of standard predicted value was judged to represent AN. In alcoholics, QTc, correlated negatively with the ratio of CV, to its standard value (r = ‐0.49, p < 0.0001). The incidence of QTc, prolongation was higher in alcoholics with AN (46.9%) than in alcoholics without AN (21.9%, p < 0.05). QTc prolongation was not observed in healthy controls. The QTc interval was significantly (p < 0.01) longer in alcoholics with AN (444 ± 20 msec) than in alcoholics without AN (426 ± 17) and in healthy controls (398 ± 18). These results suggest that alcoholism causes dysfunction of the autonomic nerves as well as worsening QT prolongation, and this may predispose such patients to sudden cardiac death.
Drinking Patterns and Problems: A Comparison of ER Patients in an HMO and in the General Population
Authors: Cherpitel Cheryl J.
Published: April 2006

The purpose of this study was to compare drinking patterns and alcohol‐related problems and associations of these variables with casualties in an emergency room (ER) population and in the general population from which these patients come. A probability sample of patients seen in all three health maintenance organization (HMO) hospital ERs in one U.S. county (N= 986) and a household probability sample of those living in the same county who reported belonging to the HMO (N = 735) were interviewed. The ER sample was more likely to report consequences related to drinking, less likely to report feeling they should cut down on their drinking, and more likely to report greater use of the ER than the general population sample. Similar associations were found between injured and noninjured in the two samples. These data lend support for the generalizability of findings of associations of alcohol and causalities obtained from ER studies to the larger general population.
Regional Distribution of Low‐Km Mitochondrial Aldehyde Dehydrogenase in the Rat Central Nervous System
Authors: Zimatkin Sergey M. , Rout Ujjwal K. , Koivusalo Martti , Bühler Rolf , Lindros Kai O.
Published: April 2006

To clarify the regional capacity of the brain to oxidize biogenic aldehydes and ethanol‐derived acetaldehyde, a quantitative immunohistochemical study of the microregional and cellular expression of low Km mitochondrial aldehyde dehydrogenase (mALDH; EC 1.2.1.3) in the rat central nervous system was undertaken, using antiserum raised in rabbit against low‐Km aldehyde dehydrogenase purified from rat liver mitochondria. mALDH‐specific immunoreactivity (IR) was observed to various extent in the majority of structures in all brain and spinal cord areas. Staining was strong in the extranuclear cytoplasm of neuronal and glial cell bodies but less pronounced in their processes and terminals, the conducting tracts, white matter and neuropile and in blood vessels. Immunostaining density was 2 to 3 times higher in neuronal perikarya as compared with neuropile. mALDH‐positive neurons were found in all brain regions, being strongest in the inferior olive and hippocampus stratum pyramidale and weakest in substantia nigra. The percentage of morphologically identifiable ALDH‐positive neurons ranged from 40% in the arcuate hypothalamic nucleus to 88% in the cerebellar Purkinje cells. A comparison of the heterogeneous expression of mALDH in various rat CNS regions and cells, as observed in the present study, with the corresponding previously published distributions of the potential acetaldehyde‐producing enzymes ADH and cytochrome P450 2E1 indicates major differences, which may help in understanding potential acetaldehyde‐mediated CNS effects of ethanol. Knowledge of the regional distribution of high‐affinity aldehyde dehydrogenase should also throw light on the neurophysiological role of local regulation of the metabolism of biogenic aldehydes in the brain.
Alcohol Use and Dependence among Employed Men and Women in the United States in 1988
Authors: Harford Thomas C. , Parker Douglas A. , Grant Bridget F. , Dawson Deborah A.
Published: April 2006

This paper provides estimates of alcohol consumption and alcohol dependence among employed men and women in the United States. Data from the 1988 National Health Interview Survey indicate that the percentages of drinkers in white‐collar occupations are higher than the percentages of drinkers in blue‐collar occupations among both men and women; however, the men and women in blue‐collar occupations who drink have a higher average daily consumption than drinkers in white‐collar occupations. DSM‐III‐R criteria were used to classify respondents as alcohol‐dependent. Consistent with an earlier survey of employed adults in Detroit, the prevalence of alcohol dependence is highest in certain blue‐collar occupations (craftsmen, laborers, and service workers among men; machine operators, laborers, and service workers among women). Directions for further research on the occupational and drinking experiences of employed men and women are discussed.
Occupational Stress, Psychological Vulnerability and Alcohol‐Related Problems over Time in Future Physicians
Authors: Richman Judith A.
Published: April 2006

This paper elaborates the conceptual frameworks and major results to date from an ongoing longitudinal study of alcohol problems in male and female future physicians. A medical student cohort was surveyed at medical school entrance and in the 2nd and 3rd years of training. Relative to life span developmental orientations, a sizable proportion of premedical school problem drinkers “matured out” of their earlier patterns after entrance into occupational training roles. Relative to occupational selection versus stress perspectives, medical school problem drinkers were equally divided between those manifesting onset prior to the initiation of training versus those manifesting onset during medical training. Overall, both male and female problem drinking declined during the preclinical years (in contrast to premedical school levels) but manifested a trend in the direction of a reversal of the previous decline after the initiation of clinical training. The major psychosocial predictor of alcohol abuse during clinical training involved social‐relational deficits or narcissistic personality styles. Moreover, this relationship was mediated by social support deficits and patient care‐related stressors. This cohort is currently being re‐surveyed in the last year of medical school and will be followed again during residency training.
Minimization* of Workplace Alcohol Problems: The Supervisor's Role
Authors: Ames Genevieve , Delaney William
Published: April 2006

Based on findings from an ethnographic analysis of an assembly plant in a large manufacturing industry, this paper delineates a conceptual framework for “minimization” that proposes to explain the interactional processes leading to systemized weakening of alcohol problem awareness and action in the unionized workplace. In the course of 50 semi‐structured interviews and observations with union representatives and management, the role of the first‐line supervisor emerged as pivotal to minimization. Individual case studies from the ethnography and responses from a survey sample of 1000 employees are used to illustrate how goals and processes of the workplace culture impede forthright action and clear lines of decision making on alcohol issues.
The Workplace and Problem Drinking as Seen by Two Novices
Authors: Brief Arthur P. , Folger Robert G.
Published: April 2006

Based on a selective review of the occupational alcoholism literature, a number of difficulties with the research regarding the effects of the workplace on problem drinking were identified. The identification of these difficulties led to an alternative model being proposed. The alternative emphasizes interactions between predispositional factors and the workplace and does not advocate continuing to search for main effects of the workplace on problem drinking. The paper closes with 10 recommendations for future research.
Life Strains, Alienation, and Drinking Behavior
Authors: Seeman Melvin , Seeman Alice Z.
Published: April 2006

This paper examines the effect on drinking behavior of chronic strains deriving from on‐going work circumstances, and intermittent strains deriving from transitions imposed by life events: unemployment; economic strain; and stress experience (e.g., death in the family, serious illness, etc.). The respondent's personal resources for coping with these life strains are also examined by way of three measures of alienation: the sense of powerlessness, self‐esteem, and social integration. The interaction of situational strains and individual alienation is a primary focus. Regression and covariance analyses, using a sample of some 500 male respondents, indicate that (1) unemployment in itself is of relatively little consequence, (2) powerlessness is the most consistent predictor of alcohol use and abuse, and (3) the combination of stress experience and high powerlessness typifies those who are most vulnerable to high drinking quantity and drinking problems.
A Rating Scale for Assessment of Alcohol Withdrawal Psychopathology (AWIP)
Authors: Bokström Katarina , Balldin Jan
Published: April 2006

For patients in alcohol withdrawal, there are several scales designed to assess physiological disturbances, but there seems to be a lack of scales for assessment of psychopathology. To develop and evaluate a rating scale for psychopathology, items from the Comprehensive Psychopathological Rating Scale (CPRS) were selected, and patients meeting the DSMR‐III‐R criteria for alcohol dependence (303.90) were rated on these items. The patients were divided into two groups according to the length of time passed since their last period of alcohol consumption. The groups are referred to as the group (n= 53) in early withdrawal, rated daily during 1 week and the group (n= 13) in late withdrawal, rated once a week for 7 weeks. To justify inclusion in the new scale, items had to either indicate psychopathology in at least half of the patients in one of the groups in withdrawal, or be sensitive to changes over time at a 0.1% level of significance. Seventeen items fullfilled one of these criteria. The scale was tested for inter‐rater reliability in a new sample of patients (n= 30) in early withdrawal. Inter‐rater reliability, as well as internal consistency, was found satisfactory. This new scale, capable of identifying psychopathology and changes over time, may be used alone or together with physiological scales to identify subgroups of patients undergoing withdrawal.
Substance Use Disorder Diagnostic Schedule (SUDDS): The Equivalence and Validity of a Computer‐Administered and an Interviewer‐Administered Format
Authors: Davis Leo J. , Hoffmann Norman G. , Morse Robert M. , Luehr John G.
Published: April 2006

In order to evaluate the equivalence of interviewer‐administered and computer‐administered forms of the substance use disorder diagnostic schedule (SUDDS), both forms were presented to 100 substance‐dependent inpatients. An additional 101 psychiatric outpatients were administered one form or the other. For patients who received both forms of the SUDDS, the percentage agreement ranged from 96% for the classification of a lifetime diagnosis of alcohol abuse/dependence to 88% for the classification of current diagnosis of alcohol abuse/dependence (kappa coefficients ranged from 0.709 to 0.865). Overall agreement with a clinician diagnosis (validity) and the two forms of administration varied from 100% for computer‐generated diagnosis of current alcohol abuseldependence to 71% for computer‐generated lifetime diagnosis of drug abuseldependence, when stratified by number of symptoms reported. No consistent differences were found in the performances of the two forms of the SUDDS, and we conclude that they may be used interchangeably.
Effect of Fluoxetine on Alcohol Consumption in Male Alcoholics
Authors: Gorelick David A. , Paredes Alfonso
Published: April 2006

To test the effect of inhibiting serotonin uptake on voluntary alcohol intake, 20 alcohol‐dependent males were housed on a locked hospital ward with 60‐ml drinks of 97.5 proof alcohol available in a fixed interval drinking decision paradigm 13 times each day. After a 3‐day, single‐blind placebo baseline period, 10 subjects each received the serotonin uptake blocker fluoxetine (up to 80 mg po daily) or placebo double‐blind for 28 days. The fluoxetine group had a 14% lower alcohol intake during the 1st week only, associated with a lower proportion of requests for alcohol and less craving for alcohol (as rated by research staff). There were no significant effects in later weeks, nor any differences in scores on the Hamilton Depression and Anxiety Scales or the Hopkins Symptom Checklist.
Effects of Alcohol on Intrauterine Oxygen Tension in the Rat
Authors: Mitchell Jerald A. , Van Kainen Barbara R.
Published: April 2006

The effects of alcohol on the availability of oxygen within the uterine lumen of rats were determined on Day 4 of pseudopregnancy. Intraluminal oxygen tension (pO2) was measured in vivo in anesthetized rats using a 22‐gauge polarographic oxygen sensor. Intrauterine pO2 was measured for 15 min before and after intravenous injection of alcohol (1.0 g/kg: 100% ethanol/saline, 1:2 v/v) or vehicle (physiological saline). Alcohol administration increased mean intrauterine pO2 (mm Hg) from a pretreatment level of 28.3 ± 2.8 to 38.7 ± 3.8 mm Hg (p < 0.05, n= 10) at 15 min postinjection. The rapid rise in oxygen tension was accompanied by increased frequency of fluctuation (peaks/hr) in intraluminal pO2 (prealcohol: 64.2 ± 8.8 vs. postalcohol 96.0 ± 7.7 peaks/hr; (p < 0.05, n= 10). Injection of saline did not alter any aspect of intrauterine pO2. During the period of measurement of luminal pO2, blood alcohol levels increased from 0 during pretreatment to 106 mg% within 10 min of injection. These results indicate that alcohol increases the availability of oxygen within the uterus during the time of endometrial sensitivity to deciduogenic stimuli and blastocyst implantation.
Selective Changes in GABAergic Transmission in Substantia Nigra and Superior Colliculus Caused by Ethanol and Ethanol Withdrawal
Authors: Peris Joanna , Coleman‐Hardee Mia , Burry Juliet , Pecins‐Thompson Melanie
Published: April 2006

One of ethanol's actions after acute exposure is anticonvulsant activity whereas withdrawal from chronic ethanol exposure increases convulsant activity. An increase in neuronal transmission in the GABAergic pathways from striatum to the substantia nigra (SN) and a decrease in GABAergic transmission from SN to superior colliculus (SC) both appear to play a major role in inhibiting seizure propagation. If this is the case, then the changes in seizure sensitivity caused by ethanol may be expected to affect GABAergic transmission in opposite ways in SN and SC. We measured the effects of in vitro ethanol on pre‐ and postsynaptic indices of GABA transmission using SN and SC tissue from both ethanol‐naive rats and rats given ethanol in their drinking water for 24 days and then withdrawn for 24 hr, a treatment that decreases seizure latency. While ethanol inhibited 3H‐ GABA release from slices of SC at low concentrations (20‐100 mM), much higher concentrations were required to inhibit release from SN (100‐500 mM). In fact, release from SN was increased by low concentrations of ethanol. Ethanol in vitro (20‐1000 mM) also inhibited specific binding of 35S‐TBPS to the GABAA receptor but this effect was similar in both potency and efficacy in SC and SN. Next, the in vitro effects of ethanol were measured in rats that had consumed an average of 9.8 g ethanol/kg body weight/day and were then withdrawn for 24 hr. Ethanol inhibition of 3H‐GABA release from SC was significantly less in ethanol‐treated rats compared to controls whereas the inhibitory effect of ethanol was increased in SN from ethanol‐treated rats. Additionally, the number of 35S‐TBPS binding sites was increased in striatum of ethanol‐withdrawn rats. There was no effect of ethanol withdrawal on number or affinity of binding sites in other brain regions. These data are consistent with the hypothesis that striatal GABA output is decreased during periods of increased seizure sensitivity. Thus acute ethanol increased release in SN and decreased release in SC, but when animals are sensitized to seizures by ethanol withdrawal, more inhibitory GABA receptors exist in striatum and release is decreased in SN and increased in SC.
Ethanol Stimulates Immunoreactive Endothelin‐1 and ‐2 Release from Cultured Human Umbilical Vein Endothelial Cells
Authors: Tsuji Shingo , Kawano Sunao , Michida Tomoki , Masuda Eiji , Nagano Kouichi , Takei Yoshiyuki , Fusamoto Hideyuki , Kamada Takenobu
Published: April 2006

The present study employed enzyme‐immunoassay to examine the effect of ethanol on endothelin‐1 and/or ‐2(ET1+2) release from human umbilical vein endothelial cells. Thirty minutes of exposure to ethanol increased the release of immunoreactive ET1+2 from cultured endothelial cells in a dose‐dependent manner. However, ethanol at concentrations of less than 400 mM did not induce any LDH release from the endothelial cells. Trypan blue exclusion test revealed that 400 mM solution of ethanol decreased the cell viability to 7.7%. Thus, ethanol was found to directly stimulate ET1+2 release from cultured human umbilical vein endothelial cells. This reaction of vascular endothelial cells against ethanol may be related to ethanol‐induced cardiovascular diseases such as hypertension, myocardial infarction and stroke, as well as fatal alcohol syndrome.
Differences in the Brain and Pituitary β‐Endorphin System between the Alcohol‐Preferring AA and Alcohol‐Avoiding ANA Rats
Authors: Gianoulakis C. , de Waele J. P. , Kiianmaa K.
Published: April 2006

The content of pro‐opiomelanocortin (POMC) mRNA was determined in the hypothalamus, as well as in the anterior and intermediate lobes of the pituitary gland of the alcohol‐preferring AA and alcoholavoiding ANA rats under basal conditions. In addition the content of β‐endorphin‐like immunoreactivity (β‐EPLIR) was measured in nine brain regions, the anterior and intermediate lobes of the pituitary gland and the serum. The content of β‐EPLIR was significantly higher in the septum and significantly lower in the amygdala, and periaqueductal gray matter of the AA rats, while there was no significant difference between the AA and ANA rats in the arcuate nucleus plus median eminence, nucleus accumbens, caudate, hippocampus, and cortex. HPLC analysis indicated no significant differences in the relative proportions of non‐acetyl and acetyl forms of β‐endorphin peptides in the hypothalamus, distinct brain regions, and anterior and neurointermediate lobes of the pituitary gland, between the AA and ANA rats. The content of POMC mRNA but not of β‐EPLIR was significantly higher in the hypothalamus and neurointermediate lobe of the AA rats, while the content of both β‐EPLIR and POMC mRNA were significantly higher in the anterior pituitary of the AA than of the ANA rats. Thus, there are genetically determined differences in the pituitary and brain β‐endorphin system between the AA and ANA rats, which may be important in controlling the differences in the voluntary ethanol consumption exhibited by these animals.
The Rate of Ethanol Absorption is Influenced by Corticosterone in Long‐Sleep and Short‐Sleep Mice
Authors: Minnick Sharon A. , Wehner Jeanne M.
Published: April 2006

Ethanol was administered by intragastric (IG) injection and absorption was measured in long‐sleep (LS) and short‐sleep (SS) mice under various conditions that alter levels of adrenal steroids. In naive mice, LS mice absorbed ethanol more quickly than SS mice. Ethanol absorption was slower in both lines of mice after adrenalectomy (ADX). Short‐term inhibition of corticosterone synthesis had no effect on ethanol absorption in either line of mice. The effect of ADX was most pronounced in SS mice at 24 hr after surgery and at 168 hr after surgery in LS mice. Therefore, the effects of various steroid replacements were examined at these times. At 24 hr after ADX, ethanol absorption was replaced to SHAM‐operated values in SS mice receiving corticosterone treatments. Likewise, in LS mice at 168 hr after ADX, corticosterone implants reversed the effects of ADX while dexamethasome was ineffective. These results support a role for corticosterone in regulation of gastric ethanol absorption and suggest that the lack of repeatability for pharmacokinetic measures of ethanol absorption and metabolism in previous human and animal studies may relate to environmental impact on stress responses.
A Recombinant Inbred Strain Analysis of Sleep‐Time Responses to Several Sedative‐Hypnotics
Authors: Wehner Jeanne M. , Pounder June I. , Parham Christie , Collins Allan C.
Published: April 2006

The results of previous studies suggested that the sleep‐time differential between long‐sleep (LS) and short‐sleep (SS) mice decreases for a series of sedative‐hypnotic drugs as lipid solubility increases. Using the LS × SS recombinant inbred (RI) strains, we have tested whether this relationship arises because of common genetic influences on the sleep‐time responses or was simply a fortuitous difference between LS and SS mice. Mice were sleep‐time tested after intraperitoneal injections of a variety of sedative‐hypnotic drugs that vary in lipid solubility including alcohols, barbiturates, chloral hydrate, and urethane. Sleep‐time values from each of these drugs were compared with ethanol‐induced sleep times in the LS × SS RI strains. Significant genetic correlations were observed between ethanol‐induced sleep time and those responses elicited by butanol, propanol, and chloral hydrate, but not by pentobarbital or secobarbital. When the partition coefficient (log P) values were compared with the genetic correlations, a significant relationship (r=–0.85) was observed. These data suggest that common genes mediate sedative‐hypnotic reactions to ethanol and some drugs resembling it in log P value, and that anesthetic agents with low lipid solubility may be working through different mechanisms than drugs with greater lipid solubilities.
Alcohol, Nitric Oxide, and Neurotoxicity: Is There a Connection?—a Review
Authors: Lancaster Francine E.
Published: April 2006

A hypothesis is presented to explain the influence of alcohol on glutamate generated excitotoxicity. Chronic alcohol exposure is reported to increase glutamate‐N‐methyl‐D‐aspartate (NMDA) receptors and calcium ion channel activity, resulting in the neurotoxicity and seizure activity associated with alcohol withdrawal in certain persons. Recent information indicates that nitric oxide is responsible for the neurotoxicity associated with excessive glutamate stimulation of NMDA receptors. Thus, it is hypothesized that nitric oxide is involved in producing the neurotoxicity and cell disturbances associated with chronic alcohol exposure.
Predictors of Alcohol Abusers' Inconsistent Self‐Reports of their Drinking and Life Events
Authors: Toneatto Tony , Sobell Linda C. , Sobell Mark B.
Published: April 2006

Although considerable research supports the veridicality of alcohol abusers' self‐reports, all studies find that some proportion of self‐reports are inaccurate. Recently, a few studies have examined variables predictive of inaccurate self‐reports and found considerable intersubject variability. The present study examined predictors of alcohol abusers' inconsistent reports of life events and drinking using test‐retest reliability data from two questionnaires. Results indicated that inconsistent self‐reports were associated with the type (i.e., objective versus subjective) and amount (i.e., more drinking involvement at the first interview was associated with greater discrepant reports at the second interview) of information to be recalled. It appears that the nature of the questions asked may be as much or more of a contributing factor to inaccurate self‐reports as subject or setting factors, especially for individuals who report high levels of alcohol use, for whom special efforts may be necessary to gather valid self‐report data.
Autism in Fetal Alcohol Syndrome: A Report of Six Cases
Authors: Nanson J. L.
Published: April 2006

This paper reports on six children who all fulfill the criteria for fetal alcohol syndrome and have a history of maternal alcohol abuse during pregnancy, and who also fulfill the criteria for diagnosis of autism. Their behavior and natural history is compared with eight contrast FAS children, of similar ages and functional levels, who were free of autistic behaviors. The autistic FAS children were all moderately or severely retarded. Autistic behavior has not been commonly associated with prenatal alcohol exposure. Clinicians need to be aware of this potential dual diagnosis so that appropriate educational and treatment resources can be employed.
Family History as a Predictor of Alcohol Dependence
Authors: Dawson Deborah A. , Harford Thomas C. , Grant Bridget F.
Published: April 2006

The effects of various levels of positive family history of alcoholism on the probability of past year alcohol dependence were investigated using a general population sample of 23,152 drinkers 18 years of age and older. Forty percent reported a positive family history. After adjustment for age, race, gender, and poverty and compared with persons with a negative family history, the odds of alcohol dependence were increased by 45% among persons with alcoholism in second or third degree relatives only, by 86% among those with alcoholism in first degree relatives only, and by 167% among those with alcoholism in first and second or third degree relatives. The effects of family history did not vary among population subgroups as defined by age, race, gender, and poverty.
Sensation Seeking, Stress Reactivity, and Alcohol Dampening Discriminate the Density of a Family History of Alcoholism
Authors: Finn Peter R. , Earleywine Mitchell , Pihl Robert O.
Published: April 2006

Data collected from 95 nonalcoholic men who had either a multigenerational (MFH), unigenerational (UFH), or negative family history (FHN) of alcoholism were subjected to a discriminant function analysis to determine how well a set of variables differentiated between the family history groups. The data‐set comprised personality measures (sensation seeking scales, neuroticism, and extroversion), measures of cardiovascular reactivity to unavoidable shock, and measures of the cardiovascular reactivity‐dampening effects of alcohol. The discriminant analyses correctly classified 62% of all subjects, 75% of MFH subjects, 47% of UFH subjects, and 63% of FHN subjects. A canonical discriminant function analysis revealed one significant dimension (canonical variable) that differentiated between family history groups. The high density (MFH) family group scored positively on this dimension, while the UFH and FHN groups had negative mean scores on this variable. A MFH of alcoholism was characterized by a pattern of increased sensitivity to the cardiovascular reactivity‐dampening effect of alcohol, cardiovascular hyperreactivity to unavoidable shock when sober, and the personality characteristic of experience seeking, which is associated with a desire for novel and unconventional experiences.
Chronic Ethanol Treatment Induces H2O2 Production Selectively in Pericentral Regions of the Liver Lobule
Authors: Misra Uma K. , Bradford Blair U. , Handier Jeffrey A. , Thurman Ronald G.
Published: April 2006

Chronic treatment with ethanol damages pericentral regions of the liver selectively, and reactive oxygen species such as H2O2 may be involved in the mechanism of hepatotoxicity. To test this idea, the effect of chronic treatment with ethanol on rates of H2O2 production was measured in tissue cylinders isolated from periportal and pericentral regions of livers from ethanol‐treated rats. Rates of hydrogen peroxide production, assessed from the oxidation of methanol to formaldehyde by catalase‐H2O2, were similar in tissue cylinders isolated from periportal regions in control and ethanol‐treated rats. In contrast, rates of H2O2 production were over 4‐fold higher in tissue isolated from pericentral regions of livers from ethanol‐treated than control animals (1.7±0.5 vs. 0.4 ±0.3 nmol/min/mg protein, respectively). Rates of H2O2‐generating acyl CoA oxidase activity were equivalent in tissue cylinders from periportal regions of livers from both groups (approximately 2 nmol/min/mg protein), but were over 2‐fold higher in tissue cylinders from pericentral regions of livers from ethanol‐treated rats than from controls. In contrast, catalase activity was increased nearly 2‐fold in homogenates from both periportal and pericentral regions by ethanol treatment while glutathione peroxidase activity was decreased significantly in both regions. These data demonstrate that ethanol increases H2O2 generation in pericentral regions of the liver lobule in part by elevating rates of peroxisomal β‐oxidation of acyl CoA compounds and are consistent with the hypothesis that local increases in H2O2 production may be involved in the mechanism of ethanol‐induced hepatotoxicity.
Isolation and Identification of Phytoestrogens from Beer
Authors: Rosenblum E. R. , Campbell I. M. , Van Thiel D. H. , Gavaler J. S.
Published: April 2006

Two estrogenic substances of plant origin have been identified in beer using gas chromatography/mass spectrometry. These phytoestrogens, daidzein and genistein, have previously been shown to be biologically active in animals. Confirming the presence of biologically active phytoestrogens in beer and their possible presence in other beverages, suggests that there may be clinically significant effect related to sustained exposure to phytoestrogens contained in alcoholic beverages.
The Effects of Maternal Ethanol Consumption on Lactational Transfer of Immunity to Trichinella spiralis in Rats
Authors: Steven William M. , Stewart George L. , Seelig Leonard L.
Published: April 2006

Transient immunity to the intestinal parasite Trichinella spiralis can be transferred from the mother to the neonate during lactation. The goal of this study was to determine whether maternal ingestion of ethanol during pregnancy and lactation inhibited expression of anti‐T. spiralis immunity in nursing pups. Groups of female rats were infected with 1000 T. spiralis L1 larva, mated, and fed either ethanol‐containing or isocaloric liquid diets and maintained on diets through pregnancy and lactation or were fed the liquid diets for 30 days before T. spiralis infection, mated, and maintained on diets through pregnancy and lactation. Pups were challenged orally with 200 T. spiralis larva at 14 days postdelivery (preweaning period) or 21 days postdelivery (postweaning period) and were sacrificed either 3 or 8 days after respective challenge. Intestinal worm counts and serum titers of anti‐T. spiralis IgG antibodies were determined for each pup. No difference in the number of intestinal worms between pups of ethanol‐treated and pair‐fed dams that received ethanol diet after T. spiralis infection was observed in the preweaning period. This was also true of pups from the dams sacrificed at 3 days after challenge in the postweaning period. However, similar pups sacrificed at 8 days after challenge showed significantly higher worm counts (decreased immunity) relative to their pair‐fed controls. Pups of dams that received ethanol containing diet 30 days prior to T. spiralis‐infection showed significantly higher numbers of intestinal worms relative to pair‐fed pups at both the preweaning and postweaning periods.

The dams receiving ethanol after T. spiralis‐infection and their pups showed significantly lower titers of specific IgG antibodies than pups of pair‐fed control animals during the preweaning period. Dams fed ethanol diet prior to T. spiralis‐infection and their suckling pups were not different from pair‐fed animals in serum IgG antibody levels at the preweaning or postweaning period. These results showed that maternal ethanol consumption can adversely influence the transfer of lactational immunity to T. spiralis in suckling neonates. This effect was greatest when ethanol was administered to the dam prior to infection of the dam with T. spiralis. The depression of lactational immunity was not completely related to alterations in specific anti‐bodies but could be associated with defects in Cell mediated immune responses.
Lactation and Prolactin Release in Foster Dams Suckling Prenatally Ethanol Exposed Pups
Authors: Subramanian Marappa G.
Published: April 2006

The effect of prenatal ethanol exposure on lactation was studied employing prenatally ethanol‐exposed pups transferred to foster dams following parturition. During pregnancy, from day 8 to term, dams consumed either standard laboratory chow (ad libitum control), or liquid diets containing 0%, 17.5%, or 35% ethanol derived calories (EDC). To equilize caloric intake, the 0% and 17.5% EDC groups were pair‐fed to rats in 35% EDC group. Following delivery, pups born to dams fed with laboratory chow (control) or liquid diets containing 0, 17.5, or 35% EDC were adjusted to eight per litter and transferred to foster dams, which had been fed laboratory chow and water ad libitum throughout pregnancy. Foster dams were implanted with an atrial catheter on day 3 of lactation. On days 6 (early lactation) and 10 (midlactation), following separation of litters from dams for a 6‐hr period, a baseline blood sample was removed via a catheter extension. Pups were weighed and returned to the dams. Subsequent blood samples were obtained 10, 30, 60, 120, and 180 min after initiation of suckling. Suckling latency and the amount of milk consumed during the 3‐hr suckling were also determined. Litters were weighed on days 2, 6, 10, and 21.

The prolactin surge in foster dams in response to suckling by prenatally ethanol‐exposed pups was not altered on day 6 of lactation. On day 10, after the initial rise, suckling‐induced prolactin was amplified in dams suckled by prenatally ethanol‐exposed pups. This may be due to either a compensatory neuroendocrine mechanism in the foster dams for adequate milk secretion in response to the poor suckling or to the shorter but more frequent suckling episodes by prenatally ethanol‐exposed pups. On day 6 suckling latency for the 35% EDC group was greater compared to control and 17.5% EDC groups and the amount of milk consumed was lower for this group on both days 6 and 10. Pups prenatally exposed to 35% EDC diet weighed less up to weaning. These results demonstrate the continued nursing difficulty experienced by offspring and the persistence of suckling‐deficits in pups caused by prenatal ethanol exposure.
Effects of Alcohol Feeding on Synthesis and Secretion of Apolipoproteins by Regenerating Rat Sciatic Nerve
Authors: Lin Renee C. , Miller Barbara A. , Mei Margaret H. , Ochs Sidney , Lumeng Lawrence
Published: April 2006

The amounts of apolipoprotein (apo) E and A1 released into the culture medium were examined in the regenerating nerves distal to a crush site following chronic alcohol feeding. Cultured minced segments of regenerating nerves taken from rats fed an alcohol‐containing liquid diet for 5 weeks released only 50% of apoE but nearly 200% of apoA1 when compared with rats pair‐fed with a control diet. The extent of decrease in medium apoE corresponded to the decrease of apoE mRNA in the nerve. Thus, chronic alcohol ingestion affects apoE synthesis of regenerating nerves by changing its mRNA level. On the other hand, apoA1 mRNA remained undetectable in regenerating and intact nerves whether the rats were fed alcohol or not. Furthermore, the amount of apoA1 released by the regenerating nerve into the culture medium was not significantly larger than that present in the nerve tissue prior to incubation. Therefore, it is most likely that apoA1 released by the injured nerve originated from the bloodstream and the increase in apoA1 content seen in the crushed nerve of alcohol‐fed rats is due to an enhanced permeability of the nerve‐blood barrier. Since the burst of apolipo‐proteins in the injured nerve is likely to play a role in nerve regeneration, the perturbation of apolipo‐protein contents in regenerating nerves by chronic alcohol consumption may contribute to the pathogenesis of alcoholic neuropathy.