bluuebunny/crossref_metadata_2025 huggingface dataset:
Regional Brain Metabolic Response to Lorazepam in Subjects at Risk for Alcoholism
Authors: Volkow Nora D. , Wang Gene‐Jack , Begleiter Henri , Hitzemann Robert , Pappas Naomi , Burr Gail , Pascani Katherine , Wong Christopher , Fowler Joanna S. , Wolf Alfred P.
Published: April 2006

The mechanisms underlying the blunted response to alcohol administration observed in subjects at risk for alcoholism are poorly understood and may involve GABA‐benzodiazepine receptors. The purpose of this study was to investigate if subjects at risk for alcoholism had abnormalities in brain GABA‐benzodiazepine receptor function. This study measured the effects of 30 μg/kg (iv) of lorazepam, on regional brain glucose metabolism using positron emission tomography and 2‐deoxy‐2[18F]fluoro‐d‐glucose in subjects with a positive family history for alcoholism (FP) (n= 12) and compared their response with that of subjects with a negative family history for alcoholism (FN) (n= 21). At baseline, FP subjects showed lower cerebellar metabolism than FN. Lorazepam decreased whole‐brain glucose metabolism, and FP subjects showed a similar response to FN in cortical and subcortical regions, but FP showed a blunted response in cerebellum. Lorazepam‐induced changes in cerebellar metabolism correlated with its motor effects. The decreased cerebellar baseline metabolism in FP as well as the blunted cerebellar response to lorazepam challenge may reflect disrupted activity of benzodiazepine‐GABA receptors in cerebellum. These changes could account for the decreased sensitivity to the motor effects of alcohol and benzodiazepines in FP subjects.
Evaluation of the Effect of Alcohol Consumption on Erythrocyte Lipids and Vitamins in a Healthy Population
Authors: Simonetti P. , Brusamolino A. , Pellegrini N. , Viani P. , Clemente G. , Roggi C. , Cestaro B.
Published: April 2006

There is epidemiological evidence that a moderate consumption of alcohol could reduce coronary heart disease. To corroborate this statement and to see how the consumption of red wine affects phospholipid and fatty acid patterns and antioxidant status, a survey was conducted on 58 adult males (20–75 years old). A questionnaire was used to discover their medical history, various constitutional and life‐style factors, food habits, and nutrient intake; and the type and amount of alcoholic intake were investigated by means of a questionnaire.

Subjects were divided into two groups of nondrinkers and average drinkers (mean 46.5 ± 4.4, range 30.2–63.4 g/day), and the effect of alcohol was made on the following variables: γ‐glutamyltranspeptidase, apolipoprotein Al, apolipoprotein B, total and high‐density lipoprotein‐cholesterol, triglycerides, and antioxidant vitamins were determined in plasma; and phospholipids the fatty acids of phosphatidylcholine (PC) and phosphatidylethanolamine total cholesterol, α‐tocopherol, β‐carotene, and retinol were determined in red blood cells (RBCs). There were no significant differences between the two groups in protein, fat, carbohydrate, retinol equivalent, a‐tocopherol content, and cholesterol/saturated fat index of their diet. Analysis of the plasma levels of biochemical variables–adjusted for age, smoking (number of cigarettes/day), and body mass index– showed a significant increase of γ‐glutamyltranspeptidase and apolipoprotein Al concentration in the average drinkers compared with nondrinkers. Plasma α‐tocopherol and retinol levels were also significantly higher in average drinkers. In the latter group, ANCOVA demonstrated a lower percentage of sphingomyelin in RBCs, with a lower sphingomyelin/PC ratio. This group also differs from the nondrinkers in RBC monounsaturated fatty acids (increased 18:1n9 and 16:1 n7 in PC) and polyunsaturated fatty acids (increase of 20:4n6 and 22:6n3 in phosphatidylethanolamine). These differences suggest that membrane fluidity may change in relation to alcohol intake.
Depression of an Inhibitory Reflex, the Masseteric Silent Period, in Recovering Alcoholics
Authors: Vernon Cynthia E. , Hirsch Judith A. , Bishop Beverly , Cowan Richard B. , York James L.
Published: April 2006

Because inhibitory deficits may contribute to motor incoordination of alcoholics, we proposed that the duration of the masseteric silent period (SP), an inhibitory reflex, might be shorter in alcoholics (ALs) than in nonalcoholics (NAs). To test this hypothesis, we measured the SP in a racially mixed group of 12 ALs and 12 NAs matched for age (31–49 years) and sex. All subjects were normotensive, had full dentition, and reported no major medical problems. Sensory and motor conduction velocities of the anterior tibialis, ulnar, and medial nerves were measured for each subject, and were not different in ALs and NAs. Jaw jerk and SP were evoked by tapping the chin manually with a rubber hammer containing a circuit to trigger the oscilloscope display of the masseter EMGs. Averaged mean latencies and durations of the SPs were not significantly different between the right and left masseters. SP latencies were significantly (0.7 msec) shorter in ALs than NAs (p < 0.01). The mean SP duration for ALs (13.9 ± 1.6 msec) was also significantly shorter than that of the NAs (24.4 ± 2.4 msec;p < 0.001). Results support the hypothesis that chronic alcoholism may interfere with inhibitory mechanisms in the CNS

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Alcohol Modulation of Immune Function: Clinical and Experimental Data
Authors: Roselle Gary A. , Mendenhall Charles L , Chedid Antonio , Moritz Thomas E. , Gartside Peter ,   the Veterans Affairs Cooperative Study Groups 119 and 275
Published: April 2006

In both animal and human studies, ethanol seems to modulate host immune function. In a variety of animal studies, ethanol has been shown to decrease lymphocyte function and number. In human studies of patients with alcoholic hepatitis, these abnormalities were also seen with specific correlation with protein malnutrition. Hepatic pathological lesions were also correlated with lymphocyte subset infiltration. However, peripheral blood lymphocytes did not correlate consistently with hepatic histopathology.
CYP2E1 and ALDH2 Genotypes and Alcohol Dependence in Japanese
Authors: Iwahashi Kazuhiko , Matsuo Yoshinori , Suwaki Hiroshi , Nakamura Kazuhiko , Ichikawa Yoshiyuki
Published: April 2006

The genotypes of the CYP2E1 and ALDH2 loci of alcoholic (alcohol dependence) and nonalcoholic (healthy) Japanese were investigated to examine the relationship between the polymorphism of CYP2E1 (C1/C2) and ALDH2 (ALDH2*1/ALDH2*2), and the susceptibility to alcoholism. There was no significant difference in C2 gene frequency between alcoholics (0.19) and nonalcoholics (controls) (0.20), whereas there was a significant difference in ALDH2 allele frequency, suggesting that, in Japanese, the C2 genotype of CYP2E1 may have nothing to do with the risk of developing alcohol dependence. However, theALDH2*1 allele may influence drinking behavior and the development of alcohol dependence. Furthermore, racial interethnic differences in the frequency of the mutated allele of the CYP2E1 gene (CJ were found, like the ALDH2 gene. Japanese healthy controls showed a significantly higher frequency of the C2 allele than did Swedish healthy controls (0.05; reported by Persson et al., FEBS Lett. 319:207‐211,1993).
Behavioral Dysfunction and Cognitive Efficiency in Male and Female Alcoholics
Authors: Nixon Sara Jo , Tivis Rick , Parsons Oscar A.
Published: April 2006

This study was conducted to examine the role of childhood behavioral disorders (CBDs) and residual attention deficit disorder (AD‐DRT) in alcohol‐related cognitive dysfunction in male and female subjects. Alcoholic (n = 44 females, 56 males) and control (n = 40 females, 40 males) subjects completed assessments that included measures of CBDs, ADDRT, and cognitive and psychosocial functioning. Cognitive tests were specifically designed to assess efficiency in function. As expected, alcoholics were inferior to controls in their cognitive efficiency [F(1,171) = 10.43, p = 0.0015]. Alcoholics reported more CBDs [F(1,161) = 12.02, p = 0.0007], regardless of sex. They also reported more ADDRT [F(1,173) = 44.12, p = O.OOOl] than did controls. There were also sex [F(l,173) = 13.31, p = 0.0004] and group by sex effects [F(1,173) = 3.93, p = 0.051. Female alcoholics reported more ADDRT symptoms than any other group. Regression equations conducted to clarify the relation between group, sex, CBDs, ADDRT, and cognitive efficiency indicated that the best predictor of cognitive efficiency was group classification (alcoholic versus control). That is, although symptoms of behavioral disorders were reported significantly more frequently by both male and female alcoholic subjects, these symptoms could not account for the cognitive impairment observed in either sex.
Low Dose of Ethanol Suppresses Mismatch Negativity of Auditory Event‐Related Potentials
Authors: Jääskeläinen Iiro P. , Lehtokoski Anne , Alho Kimmo , Kujala Teija , Pekkonen Eero , Sinclair John David , Näätänen Risto , Sillanaukee Pekka
Published: April 2006

The acute effect of a low dose of ethanol (0.5 g/kg) on attention and auditory event‐related potentials (ERPs) was investigated in 10 social drinkers using a single‐blind, placebo‐controlled cross‐over design. A dichotic listening task, in which the subjects were instructed to attend selectively to stimuli to one ear while ignoring stimuli to the other, was used. The amplitudes of N1, P2, and the mismatch negativity (MMN) were significantly diminished by alcohol. The latencies of the MMN and N2b were also significantly increased after alcohol ingestion. The novel finding of the significant (>60% reduction in amplitude) suppression of the MMN can be interpreted as indicating disturbed preconscious detection of acoustic changes outside the scope of attention. Because this is a prerequisite to an attentional shift, the MMN suppression may be related to increased risk for accidents after alcohol ingestion. The same dose of alcohol that suppressed the MMN left intact selective attention and conscious “target” detection, as reflected by the processing negativity and P3 deflections, thus suggesting that the automatic functions of human information processing are more sensitive to alcohol than the controlled, attentional functions.
Relationships between Socioeconomic Status and Drinking Problems among Black and White Men
Authors: Jones‐Webb Rhonda J. , Hsiao Charng‐Yi , Hannan Peter
Published: April 2006

We sought to examine the relationships between socioeconomic status and drinking problems within the Black and White male populations. A two‐way interaction of social class with race/ethnicity, and with drinking consequences and alcohol dependence symptoms was hypothesized among drinkers.

Drinking problems were regressed on social class, race/ethnicity, age, alcohol consumption, and drinking settings. Social class was based on a composite of respondent's income, education, and main wage earner's occupation. Two types of drinking problems were analyzed: drinking consequences and alcohol dependence symptoms.

Our hypothesis was partially confirmed. Interactions of social class with race/ethnicity and with drinking problems were observed. Less affluent Black men reported greater numbers of drinking consequences and total drinking problems than less affluent White men; the reverse was true for affluent Black and White men. Results suggest that the relationships between socioeconomic status and drinking problems may vary by race/ethnicity.
Late‐Onset Seizures in Alcohol Withdrawal
Authors: Mayo‐Smith Michael F. , Bernard Donald
Published: April 2006

Purpose: To describe the clinical characteristics of alcohol withdrawal seizures in patients treated with a standardized protocol of short‐acting benzodiazepines.

Methods: Grand ma1 seizures were prospectively identified in a cohort of 1044 patients consecutively admitted to an inpatient alcohol detoxification unit at a Veterans Affairs Medical Center. All patients received a 72‐hr structured taper of oxazepam with additional oxazepam given without limit in amount and duration in response to alcohol withdrawal symptoms.

Results: Eleven seizures occurred for an overall rate of 1.1%. All were single grand ma1 seizures. Seizures occurred from 52 to 306 hr after admission, with a mean of 122 hr (5 days). A consistent relationship between the seizures and the cessation of oxazepam was noted, with peak incidence occurring 12–48 hr after the last oxazepam dose. In no case did recurrent withdrawal symptoms or delirium tremens develop after the seizure. Patients with seizures were slightly older, more likely to have had withdrawal seizures before (50% vs. 13%, p = 0.03), and had a more severe withdrawal course than controls.

Conclusions: Seizures continued to occur at a low but measurable rate in alcohol withdrawal treated with a short‐acting benzodiazepine. Clinical characteristics of the seizures are different from that classically described in untreated patients, with the seizures being closely related to the cessation of oxazepam rather than the cessation of alcohol.
Drinking Patterns and Health Status in Smoking and Nonsmoking Alcoholics
Authors: York James L. , Hirsch Judith Ann
Published: April 2006

Alcoholics who smoked also reported that they drank more frequently and consumed more alcohol on drinking occasions than alcoholics who did not smoke, a practice that resulted in a substantially greater lifetime alcohol consumption in the smokers. Smoking alcoholics also consumed more cigarettes and reported more smoking‐related physical symptoms than social drinkers who smoked. The heart rates (HRs) of smoking and nonsmoking alcoholics were similar and both exceeded the HRs for the smoking social drinkers by ∼13 beats/min (bpm) in males and by ∼7 bpm in females. Surprisingly, correlations between HR and lifetime alcohol consumption were higher and slopes were steeper in controls than in alcoholics. HRs in a subset of the male alcoholics fell only ∼3 bpm after 24 weeks of abstinence, but changed no further over an additional 24‐week period. Taken together, the findings suggest that HRs may have been higher in this group of alcoholics before the onset of alcohol abuse and that alcohol intake contributed only slightly to the high HR.
Insulin Signaling in Chick Embryos Exposed to Alcohol
Authors: Pennington Sam N. , Shibley Ivan A. , Koochek Keyvan , Gavigan Michael D. , Monaghan John M. , Sandstrom Lorraine P. , Morgan J. Lee
Published: April 2006

Although insulin is known to be an important generator of regulatory signals during fetal growth and development, neither the immediate nor long‐term effects of alcohol (ethanol) on insulin action are well understood. In the rat, fetal exposure to alcohol has been shown to be correlated with a subsequent abnormal response to a glucose load In the neonate and adult. Further, fetal hypoplasia secondary to maternal alcohol consumption is correlated with decreased placental glucose transport and with a lowering of the glucose levels in fetal tissues. However, the fetal effects of alcohol cannot be completely overcome by glucose/caloric supplementation, suggesting that factors other than glucose transport are involved. Using an embryonic chick model that negates the factors of matemal/placental metabolism and transport, the current study found that fetal alcohol exposure markedly increased insulin binding in developing tissue, but had little effect on the binding of the insulin‐like growth factors. Competitive binding experiments revealed a marked increase in insulin receptor numbers, but no change in binding affinity as a result of the alcohol exposure. Basal uptake of 2‐deoxyglucose by fetal tissue was lowered by alcohol exposure, but incubation with exogenous porcine insulin (1 ± 10 ‐7 m) resulted in a significant increase in glucose uptake by the alcohol‐exposed embryos. The increases in insulin binding and in insulin‐dependent glucose uptake notwithstanding, exogenous insulin could not induce normal levels of ornithine decarboxylase activity in embryonic cells previously exposed to alcohol. Furthermore, insulin treatment seemed to inhibit growth in alcohol‐exposed whole embryos. Molecular changes in the insulin signaling cascade occurring as the result of alcohol exposure included an increase in specific phosphotyrosine content that was markedly decreased following insulin stimulation. The decrease in phosphotyrosine content did not seem to involve the insulin receptor substrate‐1:phosphoinositol‐3 (PI‐3) kinase complex, because alcohol‐treated embryos had significantly elevated basal PI‐3 kinase activity that was not altered by insulin exposure. In summary, alcohol‐induced growth suppression in the chick embryo is associated with several changes in insulin signaling and thus data suggest that this important mitogenic pathway is impaired as the result of fetal alcohol exposure.
Gonadal Hormones and Aggression‐Maintaining Effect of Alcohol in Male Transgenic Transforming Growth Factor‐α Mice
Authors: Hilakivi‐Clarke Leena , Goldberg Richard
Published: April 2006

We have characterized a new transgenic mouse model that offers the unique opportunity to study the biological mechanisms linking aggression to alcohol. In contrast to all other aggressive animal models, the male transgenic mice that overexpress transforming growth factor‐α (TGF‐α) maintain their highly elevated aggressive behavior following an alcohol administration. The transgenic mice also exhibit elevated plasma levels of 17β‐estradiol (E2). Animal data support the role of E2 in aggression and alcohol intake in males. Further, type 2 alcoholism is male‐limited, suggesting that gonadal hormones are important. We examined whether gonadal hormones play a role in the resistance to respond to alcohol in the resident‐intruder test of aggression among the male transgenic TGF‐α mice. As previously reported, alcohol had a biphasic effect on sham‐operated, nontransgenic controls: 0.6 g/kg increased and 2.0 g/kg inhibited their aggressiveness. Alcohol did not significantly reduce the high levels of aggression in the sham‐operated TGF‐α mice. Castration abolished the difference in aggressive behavior between the transgenic and nontransgenic male mice by reducing aggression. Alcohol did not increase aggressive behavior in these mice. Treatment with pellets releasing 0.25 mg E2 over a 60‐day period increased aggression in the castrated male TGF‐α mice and nontransgenic controls to the levels seen in intact male transgenic mice. Alcohol did not significantly alter aggressive behavior in the E2‐treated castrated mice. These findings suggest that gonadal hormones are linked to aggressive behavior and to the aggression‐altering effect of alcohol both in the transgenic and nontransgenic mice. In particular, high plasma levels of E2 may play a critical role in the failure of alcohol to alter aggressive behavior in aggressive male mice.
Equilibrative Adenosine Transport in Rat Hepatocytes after Chronic Ethanol Feeding
Authors: Wannamaker Victoria L. , Nagy Laura E.
Published: April 2006

Acute treatment of cells with ethanol in vitro inhibits adenosine uptake via equilibrative nucleoside transporters. After longer periods of exposure to ethanol in culture, rechallenge with ethanol no longer inhibits adenosine uptake. Herein, we have investigated the long‐term effects of ethanol consumption in vivo on equilibrative nucleoside transport. Rats were fed a liquid diet containing 35% of calories as ethanol (ethanol‐fed). Control rats were pair‐fed a liquid diet that isocalorically substituted maltose dextrins for ethanol. After 4 weeks of ethanol consumption, nucleoside transport was measured in isolated hepatocytes. Uptake of [3H]adenosine was lower in ethanol‐fed rats compared with control. Influx of the nonmetabolizable nucleoside analog, [3H]formycin B, was also decreased after ethanol feeding. However, neither the number of nitrobenzylthioinosine (NBMPR) binding sites or inhibition of adenosine uptake by NBMPR were affected by ethanol feeding. In controls, acute treatment of isolated hepatocytes with 100 itim ethanol inhibited [3H]adenosine uptake by 30–40%. However, in ethanol‐fed rats, acute challenge with ethanol did not inhibit [3H]adenosine uptake. These data demonstrate that long‐term ethanol feeding decreases equilibrative nucleoside transport in hepatocytes independent of a change in the number of nucleoside transporters and renders adenosine uptake insensitive to inhibition by ethanol.
Effect of Ethanol on Prostacyclin, Thromboxane, and Prostaglandin E Production in Human Umbilical Veins
Authors: Randall Carrie L. , Saulnier Jocelynn L
Published: April 2006

The purpose of this study was to determine the effects of ethanol on prostacyclin (PGE, prostaglandin E (PGE), and thromboxane (TXA2 production in perfused human umbilical veins.

PGI2, PGE, and TXA2 levels were measured from human umbilical veins perfused with either 25, 50, or 100 mM ethanol by radioimmunoassay of their stable metabolites. Alcohol content was measured by an enzymatic spectrophotometric assay. Data were analyzed by ANOVA and Fisher's Protected Least Significant Difference Test.

Ethanol decreased PGI2 production in a concentration‐dependent manner (p < 0.05). In a concentration of 25 mM, ethanol did not affect PGI2 production, whereas 50 mM decreased levels after 60 min of perfusion (p < 0.01). With 100 mM ethanol, PGI2 production was decreased after 15, 30, and 60 min of perfusion (p s < 0.05), and the TXA2/PGI2 ratio was significantly elevated at all time points (p < 0.01). Ethanol (100 mM) did not affect TXA2 or PGE production.

Reduction of PGl2 levels and the increase in the TXA2/PGI2 ratio seen after ethanol perfusion in umbilical veins may cause vascular disruption in the umbilical‐placental circulation. This may, in part, be a contributing mechanism to the teratogenic effects of ethanol.
Induction of HSP72 in Rat Liver by Chronic Ethanol Consumption Combined with Exercise: Association with the Prevention of Ethanol‐Induced Fatty Liver by Exercise
Authors: Trudell James R. , Lin Wei‐Qi , Chrystof Dale A. , Kirshenbaum Gary , Ardies C. Murray
Published: April 2006

Ethanol‐induced fatty liver in rats was attenuated by repeated running exercise, and the protective effect of exercise was associated with the synergistic expression of heat shock proteins (HSP72). Rats were placed in four groups of six. The two ethanol‐fed groups of rats received a liquid diet (Lieber‐DeCarli formulation) in which 36% of the calories were derived from ethanol. One group remained sedentary (S/E), whereas the other was trained to run on a rodent treadmill at a speed of 27 m/min, 1 hr/day, 5 days/week, for 7 weeks (R/E). Two other groups–one exercised as previously mentioned (R/C) and one sedentary (S/C)–received control‐liquid diets in which the ethanol was isocalorically substituted with a dextran/maltose mixture. The degree of fatty infiltration in liver sections stained with hematoxylin and eosin was graded on a 0–4 scale and the data analyzed by ANOVA on ranks. Ethanol significantly induced fatty infiltration in the S/E group, whereas fatty infiltration in the livers of the R/E group was not different from the S/C group. Electrophoresis and Western blotting of liver homogenates demonstrated that HSP72 was not expressed in either the S/C or S/E groups and was only slightly expressed in the R/C group. The combination of exercise and ethanol, however, resulted in an elevated expression of HSP72 in the R/E group. The content of HSP73 was unaffected by any treatment.
Role of Plasma Vasopressin in Changes of Water Balance Accompanying Acute Alcohol Intoxication
Authors: Taivainen Hanna , Laitinen Kalevi , Tähtelä Riitta , Kiianmaa Kalervo , Välimäki Matti J.
Published: April 2006

Acute alcohol intoxication causes diuresis presumably resulting from inhibition of vasopressin (also called antidiuretic hormone) release from the posterior pituitary gland. In contrast, in alcoholics during withdrawal from alcohol, vasopressin release is stimulated, resulting in water retention (antidiuresis) and dilutional hyponatremia. The purpose of this study was to evaluate the role of this triphasic response of vasopressin secretion to alcohol in normal persons. We studied eight healthy men who took part in two study sessions: one involving the ingestion of ethanol (1.2 g/kg of body weight) and the other the ingestion of the same volume of fruit juice during 3 hr from 6 to 9 PM. Starting at 6 AM the following morning, subjects were loaded with water (20 ml/kg of body weight within 15 min). During the first 3 hr of the study, ethanol intake increased diuresis, whereas from midnight to 6 AM, a phase of antidiuresis was obtained. Antidiuresis continued during water loading when the retention of water was 44 ± 6% during the alcohol experiment and 12 ± 4% during the control session (p < 0.05). During the alcohol‐induced diuresis, the plasma arginine vasopressin levels did not differ from the control experiment, but were higher during the phase of antidiuresis from 10 PM to 6 AM (p < 0.05‐<0.01). Also, after water loading at 8 and 9 AM, they were higher in the alcohol study than in the control experiment (p < 0.05). After alcohol ingestion, serum osmolality was higher than the corresponding control values from 8 PM to 2 AM (p < 0.01‐<0.001). After water loading at 9 AM, serum osmolality was slightly lower (p < 0.05) in the alcohol study than in the control study. During alcohol ingestion, urine was diluted; but, from midnight until the end of the experiment, it was more concentrated in the alcohol study than in the control study (p± 0.05‐<0.01). In conclusion, our results do not support the idea that the inhibition of vasopressin secretion is the only mechanism of alcohol‐induced diuresis. In contrast, stimulated vasopressin secretion explains, at least in part, antidiuresis and water retention that also follow alcohol intoxication in healthy persons.
Family History of Alcoholism and the Mediation of Alcohol Intake by Catalase: Further Evidence for Catalase as a Marker of the Propensity to Ingest Alcohol
Authors: Koechling U. M. , Amit Z. , Negrete J. C.
Published: April 2006

Earlier studies have suggested that catalase activity (CA) may represent a biological marker of alcohol intake in animals and in humans. An initial study was designed to rule out the possibility that CA is induced as a function of acute alcohol intake. Subjects (n= 80) were presented with either an alcohol (0.5 g/kg of body weight) or control solution, and asked to provide four 100‐μl blood samples at 0.0, 0.5, 2.0, and 24.0 hr. Results showed no differences in CA between individuals who had received alcohol, and controls, even when the effects of previous drinking history were covaried out. This lack of effect of acute alcohol intake on the possible induction of CA further supported the notion that CA may be a viable marker of alcohol intake, rather than the converse. In the second study, the relation between CA and alcohol intake was investigated in individuals with a family history (FH) of alcoholism (FH+), and in those without a family history of alcoholism (FH‐). Subjects (n= 607) completed the Michigan Alcoholism Screening Questionnaire, the MacAndrew Scale, and the Concordia University Alcohol Screening Questionnaire; answered questions concerning their FH for alcoholism; and provided a 100‐μl blood sample. Results showed that FH+ individuals had higher mean CA compared with FH‐ individuals. When individuals with FH+ were compared with those with FH‐, differences in the pattern of relation between CA and alcohol intake were observed. Although a significant relation between CA and alcohol intake was obtained for both FH‐ and FH+ individuals, this relation was significantly higher (p < 0.001) for individuals with FH+. Results from a multiple regression analyses suggested that CA in FH+ individuals made the highest single contribution to the variance, even after accounting for several additional variables. These results support the contention that CA may be a biological marker of the propensity of FH+ individuals to consume alcohol.
Brain Atrophy and Cognitive Function in Older Abstinent Alcoholic Men
Authors: Di Sclafani Victoria , Ezekiel Frank , Meyerhoff Dieter J. , MacKay Shane , Dillon William P. , Weiner Michael W. , Fein George
Published: April 2006

We used computer‐aided magnetic resonance image analysis and an age‐normed battery of neuropsychological tests to measure brain atrophy and cognitive function in 14 older abstinent alcoholic men and 11 older controls in the expectation that these subject groups would show the greatest and most persistent cerebral effects consequent to chronic alcoholism. The abstinent alcoholics exhibited cognitive impairments (primarily in memory and visual‐spatial‐motor skills) compared with the controls. In contrast, we found no difference in global cerebral atrophy between the groups, although two alcoholics had extensive atrophy compared with all other subjects. However, there was a stronger association between age and ventricular dilation in the alcoholic sample compared with controls. We conclude that a substrate other than magnetic resonance imaging‐detectable global atrophy must underlie the persistent cognitive impairments evident in the sampled alcoholics. Furthermore, if there are global atrophic changes in the brain associated with chronic alcoholism, these effects are not ubiquitous and/or may be reversible in most patients with sufficient abstinence.
Methanol in Human Breath
Authors: Taucher J. , Lagg A. , Hansel A. , Vogel W. , Lindinger W.
Published: April 2006

Using proton transfer reaction‐mass spectrometry for trace gas analysis of the human breath, the concentrations of methanol and ethanol have been measured for various test persons consuming alcoholic beverages and various amounts of fruits, respectively. The methanol concentrations increased from a natural (physiological) level of ∼ 0.4 ppm up to ∼ 2 ppm a few hours after eating about 1/2 kg of fruits, and about the same concentration was reached after drinking of 100 ml brandy containing 24% volume of ethanol and 0.19% volume of methanol.
Hepatitis C Virus in Alcoholic Patients with and without Clinically Apparent Liver Disease
Authors: Coelho‐Little M. E. , Jeffers L. J. , Bernstein D. E. , Goodman J. J. , Reddy K. R. , de Medina M. , Li X. , Hill M. , La Rue S. , Schiff E. R.
Published: April 2006

A high prevalence of antibodies to the hepatitis C virus (anti‐HCV) has been demonstrated among patients with alcoholic liver disease, whereas the prevalence of HCV viremia in these patients remains uncertain. The aims of this study were to determine the prevalence of anti‐HCV in alcoholic patients both with and without clinically apparent liver disease and to determine the presence of HCV RNA in those patients who tested positive for anti‐HCV by RIBA II (Chiron Corporation, Emeryville, CA). One hundred male patients consecutively admitted to an alcoholic rehabilitation program were included. Group 1 was comprised of 40 patients with clinically apparent liver disease. Group 2 was comprised of 60 patients without clinically apparent liver disease. Anti‐HCV was performed by a second‐generation ELISA assay and confirmed by RIBA II. HCV RNA was performed by Quantiplex assay (Chiron Corporation) and a nested reverse transcriptase‐polymerase chain reaction. No significant differences were found between the two groups with regards to age, quantity and duration of alcohol intake, or accepted risk factors for HCV. The overall prevalence of anti‐HCV in our patients was 23%, with 43% of these in group 1 and 10% in group 2. HCV RNA tested positive in 94% of the anti‐HCV‐positive patients in group 1 and in 67% of the anti‐HCV‐positive patients in group 2. These data suggest that HCV infection is an important cofactor in the pathogenesis of liver disease among alcoholic patients.
Style, Consumption, and Problem Drinking: A Measurement Model
Authors: Yu Jiang
Published: April 2006

Yu and Williford (J. Drug Issues 22:75–90,1992) report from a structural study that drinking style is the best predictor of problem drinking. This study further examines a measurement model on drinking style, alcohol consumption, and problem drinking. Four measures are specified for drinking style, three for alcohol consumption, and two for problem drinking. The maximum‐likelihood procedure through the LISREL program is used to reproduce the observed correlations by allowing correlations among systematic measurement errors. Strong associations are noted among drinking style, alcohol consumption, and problem drinking. The analysis suggests that the style of drinking should be included in research on problem drinking. Implications of the findings and future research issues are discussed.
Carbohydrate‐Deficient Transferrin as a Marker of Alcohol Abuse: Relationship to Alcohol Consumption, Severity of Liver Disease, and Fibrogenesis
Authors: Niemelä Onni , Sorvajärvi Katja , Blake Joan E. , Israel Yedy
Published: April 2006

Carbohydrate‐deficient transferrin (CDT) measurements have been widely examined as a marker of excessive alcohol consumption, yet the information on the sensitivity of this method has remained controversial. In addition, little is known of the relationship of this marker and the severity of alcoholic liver disease (ALD). To clarify these Issues, we analyzed serum samples from 373 alcohol abusers, including 200 problem drinkers with no apparent liver pathology, 173 patients with clinical or morphological evidence of ALD, and 42 healthy controls. CDT was analyzed by anion‐exchange chromatography followed by radioimmunoassay. At a specificity of 100%, the sensitivity of CDT was 36% in problem drinkers reporting a mean of 710 ± 80 (mean ± 2SE) g of ethanol/week, as compared with the sensitivities of 44% and 35% for γ‐glutamyltranspeptidase (GGT) and mean corpuscular volume (MCV), respectively. In a subgroup of problem drinkers (n= 51) with the highest ethanol intakes (1160 ± 180 g of ethanol/week) and severe dependence, the sensitivity of CDT increased to 64%, compared with 55% for GGT and 39% for MCV. In ALD, the CDT values were significantly higher than in the alcoholics with nonliver pathology. However, when such patients were classified according to the clinical, laboratory, and morphological severity of liver disease, CDT was found to be primarily elevated in those with the early stage of ALD, such that there was a significant negative correlation between CDT and the combined morphological index of disease severity (rs= ‐0.315, p < 0.05). ALD markers of fibrogenesis were elevated more frequently than CDT, showing significant positive correlations with the indices of disease severity. Current data indicates that, although CDT concentration correlates with the amount of alcohol consumed, it lacks diagnostic sensitivity in alcohol abusers consuming < 100 g of alcohol per day, thus hampering its use as a screen for consumption in community samples. The finding that CDT is increased in an early phase of ALD may prove to be of diagnostic value.
Alcohol Ingestion Impairs Host Defenses Predisposing Otherwise Healthy Mice to Pneumocystis carinii Infection
Authors: D'Souza Nympha B. , Mandujano Jose F. , Nelson Steve , Summer Warren R. , Shellito Judd E.
Published: April 2006

Pulmonary infection with Pneumocystis carinii, an opportunistic pathogen, is associated with a variety of immunosuppressive states, Including human immunodeficiency virus infection. We hypothesized that alcohol ingestion might compromise host defenses against this pathogen and, in an immunocompromised host, increase the severity of infection. This hypothesis was tested in both acute and chronic ethanol‐treated normal and CD4+ T‐cell‐depleted mice challenged with P. carinii organisms.

Normal and CD4+ T‐cell‐depleted mice were given an intraperitoneal injection of ethanol or saline 0.5 hr before P. carinii challenge and killed 3 hr later for bronchoalveolar lavage. Acute alcohol treatment decreased significantly tumor necrosis factor (TNF) activity and the number of polymorphonuclear leukocytes (PMNLs) recovered in the lavage in response to the pathogen. Depletion of CD4+ T‐cells did not potentiate the effect of alcohol on the early inflammatory response to the pathogen any further. In normal animals, in vivo interferon (IFN)‐γ pretreatment augmented significantly the P. carinii‐ stimulated lung TNF response and PMNL recruitment. However, IFN‐γ pretreatment prevented the alcohol‐induced suppression of TNF secretion without affecting the PMNL recruitment. The effect of chronic alcohol consumption on the severity of infection was studied in long‐term, alcohol‐fed normal and CD4+‐depleted mice challenged with P. carinii organisms. Lung histopathology showed that P. carinii infection was present in >60% of the alcohol‐fed mice and in none of the controls. Also, a significantly higher number of PMNLs were recovered in the lavage fluid of alcohol‐fed mice with persistent infection. There was no difference in lavage fluid and cell culture supernatant TNF and reactive nitrogen intermediates release between the two groups. CD4+ T‐cell depletion did not alter significantly the effect of alcohol on any of the aforementioned parameters.

We conclude that chronic alcohol ingestion alone induces immunosuppression sufficient to permit pulmonary infection with P. carinii. One possible mechanism for the adverse effects of alcohol on host defenses against P. carinii may be through suppressed host release of cytokines including TNF‐α and IFN‐γ.
In Utero Ethanol Exposure Retards Growth and Alters Morphology of Cortical Cultures: GM1 Reverses Effects
Authors: Laev Heljo , Karpiak Stephen E. , Gokhale Vinayak S. , Hungund Basalingappa L
Published: April 2006

Ethanol, a developmental neurotoxin, alters plasma membranes'physicochemical properties affecting embryogenesis, cell migration, differentiation, and synaptogenesis. In a previous study using a model for fetal alcohol effects, GM1 ganglioside treatment was shown to reduce ethanol‐induced accumulation of endogenous GM1 and fatty acid ethyl esters in rat fetuses. The present study was initiated to define further the in utero effects of ethanol and the capacity of GM1 treatment to ameliorate such effects. Wistar dams were exposed to ethanol (intragastrically) on gestation day (GD) 7 and GD8 and GD13 and GD14. GM1 ganglioside (10 mg/kg, im) was given 24 hr before ethanol administration. Cortical cultures were derived from GD15 and GD20 fetuses. GM1, which is highly localized on the cellular plasma membrane outer surface of CNS cells, was used as a marker molecule to assess cell integrity. Cholera toxin/ antitoxin/fluorescence immunohistochemistry was used to localize GM1. Results indicate that the brief in utero exposure to ethanol affected cell growth and morphology. A marked retardation of cell development and arborization was observed as early as 24 hr after plating. Ethanol‐exposed cells evidenced considerably altered GM1 localization. Such alterations likely reflect losses of membrane integrity. These in utero ethanol‐induced pathologies are remarkably diminished in cultures derived from ethanol‐exposed fetuses of dams treated with GM1.
Chronic Prenatal Ethanol Exposure Alters the Normal Ontogeny of Choline Acetyltransferase Activity in the Rat Septohippocampal System
Authors: Swanson Douglas J. , King Michael A. , Walker Don W. , Heaton Marieta B.
Published: April 2006

In animal models of fetal alcohol syndrome (FAS), the hippocampus has been shown to be especially sensitive to the effects of prenatal ethanol exposure, exhibiting neuronal loss and alterations in neuritic process elaboration. We have characterized the influence of chronic prenatal ethanol treatment (CPET) on the postnatal expression of choline acetyltransferase (ChAT) In the hippocampus and the septal area that contains neurons that provide the primary cholinergic innervation to the hippocampus. On gestation days 1–22, pregnant rats were either fed an ethanol‐containing liquid diet, pair‐fed a calorically equivalent sucrose‐containing diet, or given rat chow ad libitum.

In Chow control animals, the ontogenetic progression of ChAT activity in the septal area and hippocampus was characterized by a significant period of upregulation during the 2nd and 3rd postnatal weeks, exhibiting an approximate 5‐fold increase (septal area) and 7‐fold increase (hippocampus) by postnatal day 21 (P21). At P14, ethanol exposure reduced septal and hippocampal ChAT activity levels, compared with those of pair‐fed offspring. ChAT activity reached control levels by P21 in ethanol‐exposed pups, suggesting that the earlier decline in activity may reflect a delay in the ontogenetic upregulation. In addition, there was a trend toward increased septal and hippocampal ChAT activities at P1 and P7 in both liquid diet groups. This liquid diet‐stimulated increase may mask the effects of ethanol on early postnatal ChAT expression in the septohippocampal system.

The results suggest that prenatal ethanol exposure may influence factors that regulate the developmental expression of ChAT in the septohippocampal system. In addition, we found a close relationship between the effects of CPET on litter birthweight and subsequent postnatal body and brain weight measures, but not between litter birthweight and ChAT activity from individual animals. This may imply that the influence of ethanol exposure on ChAT activity is independent of its effects on postnatal brain or body growth. Such an observation of neurochemical dysfunction in the absence of morphological indices frequently used to diagnose alcohol‐related deficits could have potential clinical significance, both in the diagnostic and therapeutic realms.
Low‐Density Lipoprotein Reconstituted with Fatty Acid Ethyl Esters as a Physiological Vehicle for Ethyl Ester Delivery to Intact Cells
Authors: Bird David A. , Szczepiorkowski Zbigniew M. , Trace Vickie C. , Laposata Michael
Published: April 2006

Fatty acid ethyl esters (FAEEs), esterification products of ethanol and tatty acids, have been found selectively in the organs damaged by ethanol abuse, and on that basis have been implicated as contributors to ethanol‐induced organ damage. To directly assess the cytotoxic potential of FAEEs with intact cells in a physiological system, solubility must be achieved for these highly nonpolar lipids in aqueous medium. After ethanol ingestion, FAEEs can be found within low‐density lipoproteins (LDLs). Therefore, to achieve solubility with FAEEs bound to a naturally occurring lipid carrier, we developed a method for FAEE solubilization and delivery to cells in culture. We synthesized radiolabeled FAEEs and incorporated them into human LDL particles that bind to LDL receptors and deliver FAEEs to intact c ells. Ethyl palmitate and ethyl oleate were incorporated into LDLs yielding molar ratios of FAEEs to LDLs of 2,153 ± 249 and 4,208 ± 403, respectively. LDL reconstituted with FAEE had the same electrophoretic mobility on agarose gel electrophoresis as native LDL, Indicating that the reconstituted LDL (rLDL) was not oxidatively modified. Quantitative analysis of the solubilization of FAEEs in aqueous medium was investigated by adding FAEEs to tissue culture medium either directly or reconstituted in LDL at a concentration of 27 μM. The percentage of FAEE quantitated was 40.0 ± 2.5% and 89.3 ± 0.6% for FAEEs added directly and in rLDLs, respectively. After sterile filtration of these two media, the percentage of FAEE that remained was 11.8 ± 1.3% (direct addition) and 74.9 ± 1.3% (addition within rLDL), further demonstrating that the LDL particle did solubilize the FAEE. There was a linear relationship between the amount of rLDL in the medium and the amount of FAEE incorporated into the cells. Finally, native LDL (1:21 for rLDL:native LDL) was shown to decrease the uptake of ethyl oleate rLDL by HepG2 cells by 23.1 ± 3.1%, indicating the involvement of a receptor in rLDL uptake. Use of LDL reconstituted with FAEE as a solubilized form of the ester will permit in vivo and in vitro studies assessing the physiological and pathological roles of these potentially toxic ethanol metabolites.
Sucrose, Ethanol, and Sucrose/Ethanol Reinforced Responding under Variable‐Interval Schedules of Reinforcement
Authors: Files Forrest J. , Samson Herman H. , Brice Gary T.
Published: April 2006

Adding sweeteners to ethanol solutions is a common method of inducing rats to consume ethanol. However, it has usually been assumed that it is the sweet taste and/or the calories contained in the sweet solution that controls consumption. The present experiment examined the role of ethanol in controlling responding reinforced by ethanol or an ethanol/sucrose mixture compared with sucrose solutions of various concentrations. After initiation to self‐administer 10% (v/v) ethanol using the sucrose‐substitution method, rats were trained to respond under a concurrent VI 5″ VI 5″ schedule. During one condition, responding on one lever was reinforced by the presentation of 10% ethanol, and responding on a second lever was reinforced by water or one of the following sucrose solutions: 1 % (w/v), 1.5%, 2%, 2.5%, 3%, and 5%. During a subsequent condition, responding reinforced by a 10% ethanol/2% sucrose mixture was compared under the concurrent schedule with responding reinforced by water, 2%, 2.5%, 3%, 5%, or 10% sucrose (w/v). The results indicated that the ethanol or ethanol/sucrose mixture maintained more responding than did sucrose solutions that were sweeter. Data support the conclusion that, after initiation, the taste and/or pharmacological effects of ethanol had become an important component of the reinforcing stimulus independent of the sweetener.
Effects of Prenatal Ethanol Exposure and Stress in Adulthood on Lymphocyte Populations in Rats
Authors: Giberson Pamela K. , Weinberg Joanne
Published: April 2006

The present study was undertaken to assess the possible interactive effects of prenatal ethanol exposure and stress in adulthood on lymphocyte populations in rat offspring, and to examine differential vulnerability of males and females to these challenges. Male and female offspring from prenatal ethanol‐exposed (E), pair‐fed, and ad libitum‐fed control conditions were exposed to a 3‐week chronic intermittent stress regimen in adulthood. Animals were exposed to two of six different stressors daily, one each at random times in the morning and afternoon, with the same pair of stressors being repeated every 4 days. Following the 3‐week stress period, lymphocytes from four compartments (peripheral blood, spleen, thymus, and cervical lymph nodes) were analyzed for expression of differentiation antigens. Data demonstrate that, whereas a number of the effects of prenatal ethanol on lymphocyte populations appeared to be nutritionally mediated, the additional challenge of exposure to stressors differentially affected animals exposed to ethanol prenatally and appeared to have effects primarily in male offspring. Stressed E males had a greater reduction in the number of pan T‐cells in the thymus and peripheral blood, compared with nonstressed E males, but showed an increased peripheral blood pan T‐antigen expression. Stressed E males also had reduced numbers of peripheral blood CD4+ T‐cells and thymic CD4+CD8+ T‐cells, compared with controls. In addition, several effects of stress were observed in animals in all three prenatal treatment groups, including decreased numbers of lymph node pan T‐ and CD4+ T‐cells and decreased numbers of total peripheral blood lymphocytes in males, increased numbers of total splenic and thymic lymphocytes in females, and increased numbers of splenic CD8+ T‐cells, as well as a decreased ratio of CD4+:CD8+ T‐cells in the lymph node and spleen in both males and females. These findings indicate that, although exposure to chronic intermittent stress in adulthood may have marked effects on lymphocyte populations across all treatment groups, specific deficits in the immune system of fetal E animals may become apparent only when these animals are subjected to the additional challenge of stress. Moreover, male and female offspring may be differentially affected by the two challenges of ethanol and stress.