bluuebunny/crossref_metadata_2025 huggingface dataset:
Lower Serum Thyroxine Levels in Rats following Prenatal Exposure to Ethanol
Authors: Hannigan John H. , Bellisario Ronald L.
Published: April 2006

Fetal alcohol syndrome (FAS) is noted for poor growth, developmental delays, and mental retardation. In animals, prenatal alcohol exposure alters anatomical, physiological, and neurochemical maturation and produces behavioral changes similar to those in children. Since thyroid hormones are critical trophic factors for normal somatic and neural maturation, and since fetal thyroid hormones are profoundly affected by acute maternal ethanol administration, we hypothesized that postnatal effects of prenatal alcohol exposure may be related to abnormal thyroid hormone development. We report here that young rats exposed to alcohol in utero have significantly lower serum total thyroxine (T4) concentrations than normal and pair‐fed control rats. The results suggest prenatal ethanol exposure may compromise thyroid development in ways not attributable to undernutrition or developmental delays alone. Lowered total T4 levels may be a teratogenic outcome of prenatal alcohol exposure, which could contribute to impaired growth, altered neural organization, and behavioral dysfunction.
Alcohol and Drug Use by College Males as a Function of Family Alcoholism History
Authors: McCaul Mary E. , Turkkan Jaylan S. , Svikis Dace S. , Bigelow George E. , Cromwell Christina C.
Published: April 2006

Family history of alcoholism increases the risk for development of alcoholism in male offspring. The present questionnaire study examined self‐reported alcohol and drug use in 744 college males as a function of DSM‐IllR alcohol dependence diagnoses in first‐ and/ or second‐degree biological relatives. Substance use was most prevalent and most frequent in students with both first‐ and second‐degree alcohol‐dependent family members, was intermediate in students with only first‐degree affected relatives, and was least in students with no affected relatives. Students with both first‐ and second‐degree alcohol‐dependent relatives reported: more alcohol, marijuana, sedative, and cocaine ingestion; a younger age at first alcohol intoxication and first marijuana use; experience with less commonly used drugs; and more personal substance‐related problems as well as more family mental health care. These data have significant prevention implications for targeting at‐risk youth.
Alterations in the Regulatory Properties of Hepatic Fatty Acid Oxidation and Carnitine Palmitoyltransferase I Activity after Ethanol Feeding and Withdrawal
Authors: Guzmán Manuel , Castro José
Published: April 2006

The effects of prolonged ethanol feeding on the regulatory properties of both hepatic fatty acid oxidation and carnitine palmitoyltransferase I activity (CPT‐I) were studied in rats fed a high‐fat diet containing 36% of total calories as ethanol (ethanol group) or an isocaloric amount of carbohydrate (control group). Prolonged ethanol feeding progressively decreased CPT‐I activity and increased enzyme sensitivity and sensitization to inhibition by malonyl‐CoA in liver mitochondria. Similarly, long‐term ethanol feeding progressively increased the sensitivity of CPT‐I, as well as that of fatty acid oxidation, to inhibition by 4‐hydroxyphenylglyoxylate. Short‐term addition of ethanol or acetaldehyde to the incubations markedly increased the sensitivity of CPT‐I to inhibition by malonyl‐CoA in a subsequent assay in hepatocytes isolated from ethanol‐treated rats, but not in cells from control animals. This effect may be mediated by the ethanol‐ or acetaldehyde‐induced increase of intracellular malonyl‐ CoA levels. The present results show that ethanol feeding to rats leads to profound alterations in the regulatory properties of hepatic CPT‐I, which seem to be determinant for the decreased capacity of fatty acid oxidation by the liver in this state. Nevertheless, all the above‐mentioned alterations of the fatty acid oxidative system were reversible, disappearing after 2 to 4 days of ethanol withdrawal.
Behavioral and Subjective Effects of Ethanol: Relationship to Cerebral Metabolism Using PET
Authors: de Wit H. , Metz J. , Wagner N. , Cooper M.
Published: April 2006

This study examined the effects of ethanol on regional cerebral metabolic rate using positron emission tomography (PET). The study explored the relationship between the mood‐altering effects of ethanol and its effects on regional cerebral glucose utilization (CMRglu) in eight healthy male volunteers. In the first phase of the study, the subjects participated in a behavioral preference procedure conducted in a recreational environment to determine their responses to ethanol (0.5 g/kg) in a naturalistic setting. They then participated in three PET sessions, receiving at three to seven day intervals, in counterbalanced order, placebo, 0.5 g/kg or 0.8 g/kg ethanol. PET scans were conducted using a PETT‐VI scanner with F‐18‐2‐fluoro‐2‐deoxyglucose (FDG) as the tracer. The mood‐altering effects of ethanol were measured in both the naturalistic and the PET phases of the study. Ethanol produced comparable effects on mood in the naturalistic and the PET settings (i.e., increases in positive mood). The lower dose of ethanol produced variable effects on whole brain and regional CMRglu across subjects. There was some suggestion that certain regional metabolic changes after ethanol were correlated with subjective responses to the drug. The higher dose of ethanol decreased whole brain CMRglu in most subjects. All regions were affected about equally. It was concluded that the mood‐altering effects of ethanol are not related in a simple manner to regional changes inCMRglu.
Oxysterols and Alcoholic Liver Disease
Authors: Ryzlak Maria T. , Fales Henry M. , Russell William L. , Schaffner Carl P.
Published: April 2006

A new theory is presented implicating oxidative cholesterol metabolism and oxysterols as possible factors in the development of alcoholic liver disease. Our present studies have revealed the accumulation of cholesta‐3,5‐dien‐7‐one, 13.05 ± 2.75 μg/g (n = 8), and cholesta‐4,6‐dien‐3‐one, 2.26 ± 0.88 μg/g (n = 8) in fatty alcoholic liver, as compared wiht controls, 0.21 ± 0.12 μg/g (n = 7) and 0.3 ± 0.33 μg/g (n = 7), respectively. Acetaldehyde at 1 to 6 micromolar concentration in the blood and tissues of alcoholics cannot account for the extent of tissue damage, nor can it adequately explain liver steatosis characterized by accumulation of cholesterol and fatty acids and their esters in the liver of alcoholics known for their poor dietary habits. Oxysterols may be the primary cause for the development of alcoholic liver diseases and damage to accessory tissues.

Significantly lower levels of 7‐ketocholesterol in fatty liver, 6.8 ± 3.5 μg/g (n = 8), as compared with control, 36.85 ± 22.25 μg/g (n = 7), may be responsible for the increased cholesterol content of the alcoholic liver due to the inhibitory properties of this sterol on HMG‐CoA reductase in cholesterol biosynthesis.
Genotyping of Mitochondrial Aldehyde Dehydrogenase Locus of Native American Indians
Authors: O'Dowd Brian F. , Rothhammer Francisco , Israel Yedy
Published: April 2006

Using the polymerase chain reaction to amplify genomic DNA from hair roots, we have examined the mitochondrial aldehyde dehydrogenase (ALDH2) genotypes of 28 individuals from the South American Mapuche Indians. We have determined that individuals from this population previously reported to lack (ALDH2) activity do not show the presence of the inactive (ALDH22) allele frequently found in Orientals.
Esophageal Motor Disorder in Alcoholics: Result of Alcoholism or Withdrawal?
Authors: Keshavarzian A. , Polepalle C. , Iber F. L. , Durkin M.
Published: April 2006

Both acute and chronic ethanol consumption may cause esophageal dysmotility. In order to systematically evaluate the effect of ethanol on esophageal motility, we studied esophageal motility in 13 healthy subjects before and following acute intravenous administration of 0.8 g/kg ethanol and in chronic alcoholics within 6 hr of their last drink (n= 6) and following 24 to 48 hr of abstinence when signs of withdrawal were present (n= 13). Withdrawing alcoholics were also restudied after intravenous administration of 0.8 g/kg ethanol. Ethanol transiently decreased lower esophageal sphincter pressure (LESP) and inhibited LES relaxation in all control subjects; this inhibitory effect of ethanol on LESP in alcoholics was significantly less, indicating the development of tolerance. Ethanol moderately decreased esophageal contraction amplitude (ECA) in 10 of 13 controls and prolonged duration of contractions in all but had no effect on velocity of esophageal contractions. In contrast, ECA was significantly elevated in both groups of alcoholics, but this was significantly more marked in withdrawing alcoholics. Ethanol infusion returned ECA toward normal values in withdrawing alcoholics. Abnormal motility was noted in three intoxicated alcoholics and 10 (77%) withdrawing alcoholics. This included nutcracker esophagus in five and hypertensive LES in two. These data indicated that (1) esophageal motor dysfunction is common in alcoholics; (2) acute ethanol administration decreases LESP and esophageal contraction amplitude, whereas chronic ethanol consumption and withdrawal from ethanol increases ECA. This suggests development of a compensatory mechanism in chronic alcoholics leading to high pressure esophageal contractions during withdrawal.
Late versus Early Onset Problem Drinking in Older Men
Authors: Atkinson Roland M. , Tolson Robert L. , Turner John A.
Published: April 2006

Age at onset of problem drinking was studied in 132 older men (age 60 years and older) admitted to a VA geriatric alcoholism outpatient treatment program. Demographics, alcohol history, self reported psychological status, special treatment, and treatment compliance variables were tested for association with onset age. Late onset (defined as onset of the first alcohol problem at or after age 60) was not uncommon, occurring in 15% of the sample (29% of patients age 65 or older). Compared to earlier onset cases, late onset alcohol problems were milder and more circumscribed, and were associated with less family alcoholism and greater psychological stability. Late onset patients were also more compliant with outpatient treatment requirements; however, treatment program variables were better predictors of compliance than onset age.
Inpatient Treatment of Employed Alcoholics: A Randomized Clinical Trial on Hazelden‐Type and Traditional Treatment
Authors: Keso Lauri , Salaspuro Mikko
Published: April 2006

The first randomized clinical trial on the Hazelden‐type of treatment showed that this AA‐oriented treatment for alcoholism can result in significant improvement in drinking behavior as compared to a more traditional form of treatment.

One hundred forty‐one employed alcoholics were randomized to either Hazelden‐type treatment (N= 74) or to traditional‐type treatment (N= 67). The treatment groups were highly comparable. The bimonthly follow‐up lasted one year.

According to the COPES‐questionnaire (short form), the treatment at the Hazelden‐type institute was significantly more involving, supportive, encouraging to spontaneity and oriented to personal problems than at the traditional‐type institute. In accordance the treatment drop‐out rate was 7.9% at Hazelden‐type institute and 25.9% at traditional‐type institute (p < 0.02). The participation in outpatient treatment was significantly better after the Hazelden‐type treatment.

The proportion of those abstinent (admitted ethanol consumption, O g/day; gammaglutamyl transferase, and mean cell volume were normal) was higher at Hazelden‐type institute during the last (8–12 months) follow‐up period (26.3% vs. 9.8%, p= 0.05). Fourteen percent of the Hazeldon‐type institute patients and 1.9% of the traditional‐type institute patients stayed abstinent during the whole 1‐year follow‐up period (p < 0.05). The differences for the corresponding rates for controlled drinking (admitted ethanol consumption less than 40 g/day, GGT, and MCV normal) were in the same direction but did not reach statistical significance. Thus the Hazelden‐type treatment obtained better results in 1‐year abstinence rate than a more traditional‐type treatment.
Attributes of an Alcohol‐sensitive and an Alcohol‐insensitive Transient Potassium Current in Aplysia Neurons
Authors: Treistman Steven N. , Grant Alan J.
Published: April 2006

We describe two subtypes of transient potassium current, IA, found in two identified cells within the nervous system of Aplysia. These subtypes of IA are differentially sensitive to ethanol, since the decay of current is significantly slowed in the presence of ethanol in one cell, while IA is unaffected by ethanol at the same concentrations in the other cell. In this paper, we examine a number of parameters including temperature sensitivity of these different IAS. While both currents fulfill the criteria for being called IA, they are significantly different with respect to the kinetics of activation and inactivation, as well as recovery from inactivation. They do not differ significantly in the temperature sensitivity of a number of measured parameters, suggesting that ethanol and temperature do not act as a common locus; e.g., by affecting a bulk lipid membrane fluidity. In light of recent work describing the molecular biology of channels underlying IA, it is reasonable to assume that these IA subtypes reflect different underlying channels. This system may be useful for understanding the relationship of channel structure and function to ethanol action.
A Comparison of Sensitivity to Oxotremorine and Muscarinic Receptors in LS and SS Mice
Authors: Collins Allan C. , Campbell Stephen M. , Romm Elena , Marks Michael J.
Published: April 2006

Several studies have suggested that ethanol interacts with muscarinic cholinergic systems in the brain. In order to assess whether muscarinic systems regulate sensitivity to ethanol, the effects of oxotremorine pretreatment on sensitivity to ethanol were determined in the long‐sleep (LS) and short‐sleep (SS) mice, which were selectively bred for differential sensitivity to ethanol. In addition, the relative sensitivity of these two lines to intraperitoneally (ip) injected oxotremorine and total muscarinic receptors, as measured by quinuclidinyl benzilate (QNB) binding, M1 receptor subtypes, as measured by pizenzepine (PZ) binding, and ratios of high and low agonist affinity were measured in seven brain regions. SS mice were more sensitive to oxotremorine‐induced increases in sensitivity to ethanol but the LS mice were more sensitive to the effects elicited by ip oxotremorine injection. Because the effects of oxotremorine were blocked by scopolamine but not by methylscopolamine, it is likely that the effects of oxotremorine that were measured are centrally mediated. QNB binding did not differ between the LS and SS mice except for cortex where the SS mice exhibited slightly larger numbers. The mouse lines did not differ in the number of M1 receptors or in ratio of high to low affinity agonist sites. Therefore, it does not seem likely that differences in receptor numbers are important in regulating the differential sensitivities of the LS and SS mice to oxotremorine or ethanol. Differences in receptor coupling processes may be critically involved.
Neuropsychological Deficits in Fetal Alcohol Syndrome and Fetal Alcohol Effects
Authors: Conry Julianne
Published: April 2006

A clinical sample of 19 school‐aged native children diagnosed with fetal alcohol syndrome (FAS) or fetal alcohol effects (FAE) was compared with age‐ and sex‐matched normal controls. Results on a battery of intellectual and neuropsychological tests indicated large and significant differences between alcohol‐affected children and controls. FAS differed significantly from controls on measures of intellectual abilities, while FAE did not; FAS mean scores on these measures were significantiy lower than FAE means. For neuropsychological measures, FAS were significantly poorer than controls on most measures, while FAE showed deficits compared with controls only on grip strength. The results suggest that neuropsychological measures would be a valuable supplement to intellectual measures for the purpose of assessing alcohol effects because they are less vulnerable than intellectual measures to the influence of cultural and educational experiences.
Alcohol and Secobarbital Effects as a Function of Familial Alcoholism: Acute Psychophysiological Effects
Authors: McCaul Mary E. , Turkkan Jaylan S. , Svikis Dace S. , Bigelow George E.
Published: April 2006

Previous research has demonstrated response differences following administration of alcohol between adult males with a positive (FHP) versus negative (FHN) family history of alcoholism. These response differences are thought to reflect differences in vulnerability to dependence on alcohol. Thus, the role of positive family alcoholism history in increasing risk of addiction to a variety of drug classes might be studied by determining whether FHP subjects show different responses to drug classes other than alcohol. This was done in the present study by determining dose‐effect functions for a variety of physiological (heart rate, skin conductance, skin temperature), subjective (analog mood and drug effect, Subjective High Assessment Scale), and psychomotor measures (hand tremor, body sway, Digit Symbol Substitution Test, eye‐hand coordination, and numeric recall) in FHP and FHN college‐aged males for secobarbital (0, 100, 200 mg by mouth) and ethanol (1g/kg). FHP and FHN subjects were matched on light‐to‐moderate drinking patterns, anthropometric dimensions, age, years of schooling, and drug use. At equivalent blood alcohol levels family‐history positive subjects reported greater effects of ethanol than did family‐history negative subjects on almost all subjective measures. Following the high dose of secobarbital, FHP but not FHN subjects showed elevated subjective effects; these effects were substantially less and were evident in fewer measures than following ethanol. In contrast to effects on the subjective measures, ethanol and secobarbital produced comparable impairment in both groups of subjects for most psychomotor responses. Group differences were not obtained on any physiological measures. These data suggest that subjects with a family alcoholism history demonstrate a unique subjective response to alcohol that may partially generalize to other drug classes.
Sons of Alcoholics Report Greater Hangover Symptoms than Sons of Nonalcoholics: A Pilot Study
Authors: Newlin David B. , Pretorius Mary Beth
Published: April 2006

We investigated alcohol‐induced hangovers among college men at high and low risk for alcoholism. Thirteen sons of alcoholics reported significantly (p < 0.001) greater hangover symptoms in the past year than 25 sons of nonalcoholics. The two groups reported comparable quantity‐frequency of recent drinking. To the extent that hangover represents an acute withdrawal syndrome to alcohol, this raises the question of whether sons of alcoholics are “dependence‐prone.”
Alcohol Abuse Among Grandsons of Alcoholics: Some Preliminary Findings
Authors: Harford Thomas C. , Grant Bridget F.
Published: April 2006

Drawing upon self‐reports of family history for alcoholism, the present study compared the level of alcohol abuse among grandsons of alcoholic maternal and paternal grandfathers. Although based on a small sample of grandsons (N= 29), the results indicated a significantly higher level of alcohol abuse among maternal compared with paternal grandsons.
Relationships between Neuropsychological Test Performance and Event‐Related Potentials in Alcoholic and Nonalcoholic Samples
Authors: Parsons Oscar A. , Sinha Rajita , Williams Harold L.
Published: April 2006

Are event‐related potentials and nonconcurrently measured neuropsychological test performance correlated? Sober male and female middle‐aged alcoholics and peer controls were administered an “oddball” event‐related potential (ERP) task and several hours later, a battery of neuropsychological (NP) tests. Alcoholics performed significantly poorer than controls on NP tests. Male alcoholics had significantly altered ERP responses (N1, NdA, and P3 amplitudes) but female alcoholics did not differ on any ERP variables from controls. A number of significant correlations between ERP and NP measures were present. The most consistent findings were positive correlations between perceptual‐motor (PM) tests and the P3 amplitude at Pz in both male and female alcoholics and in male alcoholics, a negative correlation between PM tests and P3 latency at Pz, findings similar to those seen in Parkinson patients. Significant correlations were most numerous in family history positive alcoholics. The results lead to two conclusions: first, Grant's postulation that sober alcoholics may manifest an intermediate duration organic mental disorder is supported; second, given the lack of ERP differences in the females, ERP measures should not be considered as being causally related to NP performance.
Comparison of the Self‐Administered Alcoholism Screening Test (SAAST) and the Khavari Alcohol Test (KAT): Results from an Alcoholic Population and Their Collaterals
Authors: Loethen Gary J. , Khavari Khalil A.
Published: April 2006

This study examined the reports of patients and their collaterals on drinking practices, as measured by the summary scale of the Khavari Alcohol Test (the annual absolute alcohol intake, AAAI) and alcohol related behavioral patterns, as assessed by the Self‐Administered Alcoholism Screening Test (SAAST). In‐ and outpatients from two Milwaukee area substance abuse treatment hospitals, and a number of their collaterals, participated in this study. Patients' and collaterals' responses on the AAAI and the SAAST were compared through the use of a paired t test. Results indicated no significant differences between patients' self‐reports compared with collateral reports, and demonstrated a direct relationship on the AAAI (two tailed p < 0.001) and SAAST (two‐tailed p < 0.001). Self‐reports of patients who volunteered collaterals compared with self‐reports of patients who did not volunteer collaterals also showed no significant differences on the AAAI or the SAAST, demonstrating consistency of reporting whether the patients believed their reports would be compared with information provided by a collateral or not. The AAAI and the SAAST corroborated in their diagnoses of patients as suffering from alcoholism (r = 0.515, p < 0.001). Multivariate analysis revealed no significant effect of demographic variables on either the AAAI or the SAAST. This study shows: (a) Impressive concordance between patient and collateral reports; (2) apparent intactness of memory, and little evidence of denial, as measured by the instruments; and (3) the efficacy of measures such as the AAAI and the SAAST, two vastly different scales measuring dimensions of alcoholism.
The Potentiating Effects of Ethanol on the Blue Light Depolarization of the Retinal Pigment Epithelium
Authors: Pautler E.L. , Beezley D.
Published: April 2006

The retinal pigment epithelium (RPE) is the site of two major effects of ethanol. In humans, ethanol produces a slow damped oscillation in the steady electrical potential of the eye, which is generated primarily by the RPE. It has also been shown that ethanol potentiates the reversible, depolarizing effect of blue light on the transepithelial potential (TEP) of the isolated RPE. The present study demonstrates that in addition to the depolarizing effect of blue light on the TEP, a secondary, compensatory potential arises, which functions to maintain the TEP. The magnitude of the secondary response varies somewhat among preparations. It appears that ethanol eliminates or reduces the secondary, compensatory potential change which results in a large depolarization of the TEP when the RPE is irradiated with blue light.

Microelectrode studies reveal that ethanol hyperpolarizes both the apical and basal membranes of the RPE with a greater effect noted in the apical membrane. This would account for the corneal positive potential elicited by ethanol in the human eye. Brief exposures (2–3 min) of blue light, after administration of 0.5% ethanol, results in a large (25–30 mV) depolarization of both membrane potentials as compared with 3 to 5 mV in untreated tissue.

On the basis of our observations, it is hypothesized that some of the potentiating effects of ethanol in combination with other agents may result from an interference with a cellular adaptive response to impaired respiration rather than an additive effect on a common mechanism.
Formation of the 37KD Protein‐Acetaldehyde Adduct in Liver During Alcohol Treatment is Dependent on Alcohol Dehydrogenase Activity
Authors: Lin Renee C. , Lumeng Lawrence
Published: April 2006

Protein‐acetaldehyde adducts (protein‐AAs) are formed in vivo during chronic alcohol ingestion. These protein‐AAs reported thus far include a 37KD protein‐AA in liver cytosol, cytP450IIE1‐AA in hepatic microsomes, hemoglobin‐AA, and serum protein‐AAs. It has been postulated that acetaldehyde or perhaps a reactive acetaldehyde radical generated by the microsomal ethanol oxidizing system (MEOS or cytP450IIE1) explains the formation of the cytP450IIE1‐AA. The source of acetaldehyde responsible for the formation of the cytosolic 37KD protein‐AA has not been determined. In this report, we have examined the effects of pyrazole (an ADH inhibitor) and cyanamide (an aldehyde dehydrogenase inhibitor) on the formation of the 37KD liver protein‐AA in vivo and in vitro. It was found that feeding rats with an alcohol‐containing liquid diet supplemented with cyanamide enhanced while a diet supplemented with pyrazole completely abolished the formation of the 37KD liver protein‐AA. The liver of rats fed the pyrazole supplemented alcohol‐containing diet showed significantly higher content of cytP450IIE1 than that of rats fed the diet containing alcohol alone. On the other hand, feeding the cyanamide supplemented alcohol‐containing liquid diet did not further enhance the content of cytP450IIE1. Similarly, adding cyanamide to the culture medium enhanced while adding 4‐methylpyrarole inhibited the production of the 37KD protein‐AA by cultured hepatocytes even though the combination of alcohol and 4‐methylpyrazole increased the content of cytP450IIE1 2‐fold over that in control cells. These results demonstrate that the formation of the 37KD liver protein‐AA is dependent on ADH and not on MEOS.
Pattern and Duration of the Inhibitory Effect of Alcohol Administered Acutely on Suckling‐Induced Prolactin in Lactating Rats
Authors: Subramanian Marappa G. , Chen Xiao Guang , Bergeski Barbara A.
Published: April 2006

We have characterized the pattern and duration of the inhibitory effect of acute alcohol administration on suckling‐induced prolactin (PRL) release in the lactating rat. On day 2 of lactation, litters were adjusted to eight pups. On day 6, dams were implanted with an atrial catheter and experiments were conducted on day 10 of lactation. Pups were removed from the dams at 0800 hr. An extension tube filled with heparinized saline was attached to the catheter at 1300 hr. At 1400 hr, a preinfusion (PRE 0) blood sample was removed and was followed by infusion of saline (control) or alcohol in saline (0.5, 1.0, 2.0, 2.5 g/kg body weight doses) solutions. Following the removal of a postinfusion (POST 0) blood sample, pups were returned to the mother. Subsequent blood samples were obtained 10, 30, 60, 120, and 180 min after initiation of suckling. In separate groups, the effects of alcohol on basal PRL were studied by collecting blood samples PRE 0, POST 0 and 20,40,60,80,100, and 120 min following infusion of saline or alcohol in saline to lactating rats also separated from their pups for 6 hr.

Alcohol infusion did not after basal PRL. However, suckling‐induced PRL was inhibited at 10, 30, 60, and 120 min of suckling by alcohol administered at doses > 1.0 g/kg body weight. After 180 min of suckling, plasma PRL levels were comparable among groups. The suckling latency for the 2.5 g/kg body weight alcohol group was greater than for other groups, but the quantities of milk consumed during the 3‐hr suckling period were comparable. The blood alcohol clearance rates expressed as mg/kg/hr were 220 ± 16, 342 ± 18, and 385 ± 24 for 1.0, 2.0, and 2.5 g/kg/body weight doses, respectively. The growth rate of the pups are judged by the litter weight on days 2, 7, 14, and 21 of lactation, did not differ.

The data indicate that alcohol (administered acutely) does not affect the basal plasma PRL in lactating rats. In contrast, suckling‐induced PRL release is inhibited, and this inhibitory effect lasts approximately for 2 hr for the highest alcohol dose (2.5 g/kg body weight) employed. Further, it was also observed that a blood alcohol concentration of 65 mg/dl or greater is necessary to exert the inhibitory effect on suckling‐induced PRL release.
Acute Alcohol Ingestion Reduces Fatty Acid Extraction of the Heart, Liver, and Small Intestine
Authors: Carter Edward A. , Barli‐Kovach Martha , Elmaleh David , Livni Eli , Strauss H. William
Published: April 2006

Ethanol may have profound effects on both the distribution of perfusion and substrate utilization by the liver and heart due to its vasodilating properties and the generation of high levels of circulating acetate and lactate. Since fatty acids are highly extracted by the heart and liver under normal circumstances, changes in the relationship of perfusion/fatty acid uptake may be a sensitive indicator of both altered perfusion and changes in metabolic substrate availability. To test this hypothesis, studies were performed in rats fed 3.1, 6.2, and 9.3 g/kg doses of ethanol. Fatty acid uptake was estimated with a 3‐methyl substituted reagent with a chain length equivalent to 17 carbons. The methyl group in the three position prevented β oxidation and prolonged the residence of fatty acids in the tissue. Eighteen hours after acute alcohol administration, fatty acid uptake was reduced in the heart and the small intestine; in the liver uptake was increased or unchanged. Acute ethanol administration also resulted in increased perfusion, as indicated by enhanced uptake of 201thallium by the heart, liver, and small intestine. The fatty acid extraction of the heart, liver, and small intestine, defined as the concentration of fatty acid divided by the concentration of 201thallium, was markedly decreased by alcohol ingestion. These alcohol effects were dose‐dependent and temporally related. The data suggest that ethanol ingestion could potentially alter heart function during exercise or following a prolonged fast, when the heart relies primarily upon fatty acids extracted from the circulation to generated adenosine triphosphate (ATP).
Perspectives on the Pathophysiology of Fetal Alcohol Syndrome
Authors: Randall Carrie L. , Ekblad Ulla , Anton Raymond F.
Published: April 2006

Fetal alcohol syndrome (FAS) is a major known cause of fetal malformations and mental retardation. Prevention/intervention of FAS can only be achieved with identification of the mechanisms by which alcohol induces birth defects. The purpose of this paper is to discuss the data on possible mechanisms of FAS, and to give a number of suggestions for future research areas.
Ethanol Induced Morphologic Alterations During Growth and Maturation of Cardiac Myocytes
Authors: Adickes Edward D. , Mollner Teresa J. , Lockwood Susan K.
Published: April 2006

Alteration of growth and development of cells exposed to ethanol during embryogenesis contributes to dysmorphism. The mechanism(s) of these alterations remains an enigma. This paper describes studies of an in vitro cardiac myocyte model in which the major effort was to investigate growth and development parameters in an obligate interacting multicellular system. The well defined events of in vitro myogenesis allow for documentation or dysgenesis and altered growth in the presence of the teratogen, ethanol. The cells exposed to ethanol did not mature morphologically or functionally compared with controls. Increasing concentrations of ethanol appear to have a graded damaging effect. The greater the concentration of ethanol the more profound the dyssynchronous growth. The morphologic correlates were multinucleation, and alteration in the ultrastructural organization of cell‐cell contacts and myofilaments. Correlation of these findings with those observed in dysgenic muscle of human infants and rat pups exposed to ethanol in vtero, may provide at least a partial understanding of the teratogenic manifestation of ethanol in embryogenesis and organogenesis.
Dichotic Asymmetries in Aging and Alcoholic Subjects
Authors: Ellis Ronald J.
Published: April 2006

It has been suggested that certain cognitive changes found both with aging and with chronic alcoholism are accompanied by alterations in hemispheric functional asymmetries. One prevalent view states that these well‐delineated cognitive changes are directly related to a selective disruption of right hemisphere function. The present study tested this hypothesis using dichotic listening measures of functional asymmetry. Both alcoholics and older nonalcoholics evidenced patterns of cognitive preservation and impairment similar to those seen in patients with known right hemisphere dysfunction. Nevertheless, dichotic listening findings did not reveal any selective effect on the right hemisphere, as previously proposed. The dichotic studies supported the view that both hemispheres are affected by aging and alcoholism. Patients with right hemisphere lesions demonstrated characteristic and predictable changes in dichotic asymmetries, illustrating the reliability of the dichotic measures as indices of hemispheric function.
Antioxidant Protection Systems of Rat Lung after Chronic Ethanol Inhalation
Authors: Rikans Lora E. , Gonzalez Larry P.
Published: April 2006

The effect of chronic ethanol administration on pulmonary antioxidant protection systems was investigated in male Sprague‐Dawley rats exposed to room air or room air containing ethanol ethanol vapors for 5 weeks. Blood ethanol concentrations in ethanol‐exposed rats were usually between 200 and 300 mg/dl. Glutathione, vitamin E, and malondialdehyde concentrations were measured in lung homogenates, and antioxidant enzyme activities (catalase, glutathione peroxidase, Cu/Zn‐superoxide dismutase, glutathione reductase) were determined in the supernatant fractions. For comparison, the measurements were also made using liver fractions. Ethanol treatment increased the activities of catalase (117%) and Cu/Zn‐superoxide dismutase (25%) in lung but not in liver. Although chronic ethanol inhalation lowered hepatic glutathione (19%) and hepatic vitamin E (30%), there was no increase in malondialdehyde content in either liver or lung of ethanol‐exposed rats. The elevation of pulmonary antioxidant enzyme activities could be interpreted to mean that lung is a target for ethanol‐induced oxidative stress. However, as there was no loss of pulmonary GSH or vitamin E and no increase in malondialdehyde formation, it appears that long‐term ethanol exposure did not produce a significant degree of oxidative stress in rat lung.
The Generation of Cytotoxic T Lymphocytes Against Acetaldehyde‐modified Syngeneic Cell
Authors: Terabayashi Hidetaka , Kolber Michael A.
Published: April 2006

The major metabolic product of ethanol is acetaldehyde. It is highly reactive with proteins. In situ this modification is significant enough to generate an antibody response. Whether an effector cellular immune response can be generated against these acetaldehyde modified adducts on syngeneic cells is not known. In this paper we have demonstrated in the murine system that acetaldehyde modified splenic cells can generate cytotoxic T lymphocytes (CTL). These CTL are specific for the acetaldehyde modified syngeneic cells, and not acetaldehyde modified allogeneic cells. The ability of the CTL to lyse specific targets is dependent on the formation of stable acetaldehyde adducts. Cold target inhibition studies reveal that modified syngeneic cells can inhibit lysis as effectively as unmodified cells. Therefore, the present study lends support to the hypothesis that acetaldehyde modified cells can generate a cellular immune response and may do so in pathologic states.
Differential Effects of Norepinephrine on Phosphatidylinositol 4,5‐Bisphosphate Stimulated Hydrolysis in Brains of Mice Genetically Selected for Differences in Ethanol Sensitivity
Authors: Weiner Eric A. , French Thomas A. , Baker Rodney C. , Masserano Joseph M.
Published: April 2006

The effects of norepinephrine on phosphoinositide turnover were evaluated in five brain regions of the long sleep (LS) and short sleep (SS) mice. These mice were selectively bred for differences in central nervous system sensitivity to ethanol with the LS exhibiting much greater sensitivity to a hypnotic dose of ethanol than the SS, as determined by the ability of the mice to regain their righting reflex. Norepinephrine (10‐3 M, 10‐4 M, and 10‐5) significantly increased phosphoinositide turnover in the hippocampus, hypothalamus, locus ceruleus, cerebellum, and cortex within each line of mice. Basal and norepinephrine‐stimulated phosphoinositide turnover were significantly higher in the SS mice as compared with the LS mice in the cerebellum and cortex but not the other brain regions. Incorporation of 3H‐inositol into 3H‐phosphatidylinositols was not different between SS and LS mice in the cerebellum and cortex. The greater norepinephrine‐stimulated phosphoinositide turnover in the cerebellum and cortex of the SS versus the LS mice may contribute to the CNS sensitivity to ethanol in these two lines of mice. However, ethanol (500 mM) had no effect on basal or norepinephrine‐stimulated phosphoinositide turnover in any of the five brain areas examined in the LS and SS mice.
ABO Blood Group Differences in Bone Mineral Density of Recovering Alcoholic Males
Authors: Davidson Bert J. , MacMurray James P. , Prakash Ved
Published: April 2006

Since ABO blood group differences are associated with varying responses to many diseases, ABO blood type and bone density were studied in 39 recovering male alcoholics, comparing those with blood type O and non‐O. The type O subjects had significantly higher bone densities as measured by quantitative computed tomography of the vertebrae than the non‐O subjects (175.4 ± 8.5 and 140.7 ± 7.6, respectively, p= 0.004). There were no differences in age and indices of their alcoholism. Using multiple stepwise regression analysis, neither race nor maximal amount of alcohol consumed appeared to contribute to the differences in bone density. Only age, number of years of regular alcohol use and ABO blood type were determinants of the bone density differences. The ABO blood type contributed 20.3% to the differences in bone density (p= 0.001). The patients with non‐O blood type lost a significant amount of bone with advancing age (r=–0.76, p= 0.0001) while those with blood type O did not (r=–0.37, p=–0.11). We conclude that, although alcoholism is a factor in the development of osteopenia, in males the ABO blood group status plays a significant role in the maximal mineralization of the skeleton and the amount of bone resorption during ageing, independent of alcohol abuse.
Effect of Abstinence from Alcohol on the Depression of Glutathione Peroxidase Activity and Selenium and Vitamin E Levels in Chronic Alcoholic Patients
Authors: Girre C. , Hispard E. , Therond P. , Guedj S. , Bourdon R. , Dally S.
Published: April 2006

Glutathione peroxidase activity and selenium and vitamin E levels were measured in the plasma and erythrocytes of 25 chronic alcoholic patients without liver cirrhosis before and after 14 days of abstinence from alcohol, and compared with the levels in 25 sex‐and age‐matched healthy controls. Before abstinence, all three levels were shown significantly depressed in the alcoholic patients compared with the controls, in both plasma (80, 71, and 89% of control values) and erythrocytes (68, 70, and 83% of control values). After a 14‐day abstinence period with no dietary supplementation, a trend towards normalization was noted in erythrocyte (vitamin E and glutathione peroxidase 74 and 91% of control values respectively), in whole blood selenium (82%) and plasma in vitamin E (74%). However, plasma selenium and glutathione peroxidase values were lower than pre‐abstinence values (76% and 86% of control values respectively).

Our results point to a deficiency in the antioxidant defense system of chronic alcoholics before the occurrence of severe liver disease. This lack of protection against lipoperoxides is all the more important in circumstances like chronic alcohol consumption, in which lipid peroxidation is known to increase. However, the present study also demonstrated that during 14 days of a normal diet free of ethanol, a rapid trend occurred towards the normalization of the factors.
Cutaneous Vasomotor Sensitivity to Ethanol and Acetaldehyde: Subtypes of Alcohol‐Flushing Response Among Chinese
Authors: Yu Peter H. , Fang Chiung‐Yao , Dyck Lillian E.
Published: April 2006

A cutaneous test has been applied in examination of the flushing response to ethanol and acetaldehyde in 402 Chinese of Han ethnicity. Using this noninvasive method, five response subtypes have been observed: (A) fast flushing to both ethanol and acetaldehyde; (B) fast flushing only to ethanol but not to acetaldehyde; (C) slow flushing to ethanol only; (D) no response either to ethanol or to acetaldehyde; (E) vasoconstriction to ethanol, or to both ethanol and acetaldehyde. A total of 94% in subtype (A) are reported to be flushers, while only 25% was reported in subtype (D). Other physiological responses, such as tachycardia, dizziness, headache, drowsiness, and nausea are less frequent after alcohol ingestion. The recent history of consumption of alcohol of the subjects in different subtypes was also obtained. Although alcohol‐induced flushing is thought to be a deterrent factor to heavy consumption of alcohol, the frequency of drinking of alcoholic beverages was not found to be different between flushers and nonflushers.
Prenatal Alcohol Exposure and Language Development
Authors: Greene Tom , Emhart Claire B. , Martier Sue , Sokol Robert , Ager Joel
Published: April 2006

The effects of fetal alcohol exposure on language and speech acquisition were investigated in a cohort of socioeconomically disadvantaged urban children. Language development was assessed by instruments derived from the Expressive and Receptive Scales of the Sequenced Inventory of Communication Development (SICD) at 1, 2, and 3 years, and by indices constructed from a taped speech sample at age 2 years. Three indices of maternal drinking were supplemented with birth weight and a tally of craniofacial anomalies as early indicators of fetal alcohol damage. No statistically significant relationships were found between the alcohol and language indices after statistical control for confounding variables. The anomalies tally was marginally related to reduced language scores. The statistical significance of this relationship, depended, however, on a single child with the characteristics of fetal alcohol syndrome. The pattern of results suggested that the anomalies tally, and to a lesser extent birth weight, are more sensitive indicators of fetal alcohol exposure than subsequent language development.
Serum β‐hexosaminidase and α‐mannosidase Activities as Markers of Alcohol Abuse
Authors: Wehr Hanna , Czartoryska Barbara , Gorska Danuta , Matsumoto Halina
Published: April 2006

In 25‐alcohol‐dependent patients in whom detoxication treatment has been introduced serum total β‐hexosaminidase, thermostable β‐hexosaminidase, α‐mannosidase and γ glutamylotransferase (GGT) and serum high density lipoprotein (HDL) cholesterol were determined during alcohol withdrawal. The assays were also performed in a group of dependent individuals after a 1 month or longer period of abstinence. Marked increase in β‐hexosaminidase activity was observed in intoxicated patients. The activity decreased rapidly after the cessation of drinking, resembling the decrease in HDL cholesterol level in its dynamics. The α‐mannosidase activity rise was less pronounced and its normalization was slow, similar to the GGT activity normalization rate. The rise of ã‐hexosaminidase activity was mostly due to the thermostable component of the enzyme. Total β‐hexosaminidase or thermostable β‐hexosaminidase activity determinations appear to be simple and reliable markers of alcohol abuse.
Age‐Dependent Differences in the Thermoregulatory Response of the Immature Rat to Ethanol
Authors: Spiers Donald E. , Fusco Laura E.
Published: April 2006

Major improvement in the homeothermic ability of the rat occurs during the first 2 weeks of postnatal development. Changes in thermoregulatory responsiveness to a single injection of ethanol (EtOH) may occur during this period immature rats (2‐3, 8‐9, and 14‐15 days of age) were administered either saline or EtOH (2 or 4 g/kg BW ip) at thermoneutral ambient temperatures (Ta). In one experiment, metabolic rate (MR) and body temperatures (colonic and skin) were recorded for 1‐3 hr postinjection. A second experiment determined blood EtOH concentration in rats from the 3 age groups over an 8‐hr period following injection of EtOH. 4 g EtOH/kg produced few significant reductions in thermoregulatory function of 2‐3 day‐old rats, but decreased MR by 16% and colonic temperature by 0.5‐0.7OC in 8‐15 day‐old animals. 2 g EtOH/kg had no effect on 8‐9 day‐old rats, but reduced MR and colonic temperature in rats aged 14‐15 days. In every case, the hypothermic response to EtOH was correlated with a reduction in MR. Back and abdominal skin temperatures decreased with colonic temperature, and tail skin temperature indicated EtOH‐induced vasoconstriction in older rats. Blood EtOH concentrations were similar in the three age groups during the first 2 hr postinjection and did not explain differences in metabolic response. The magnitude and duration of thermoregulatory responsiveness to EtOH increases with age in the immature rat.
The Effects of Prenatal Alcohol Use on the Growth of Children at Three Years of Age
Authors: Day N.L. , Robles N. , Richardson G. , Geva D. , Taylor P. , Scher M. , Stoffer D. , Cornelius M. , Goldschmidt L.
Published: April 2006

In this prospective study of substance use during pregnancy, women were interviewed in their 4th and 7th prenatal months, and women and children were assessed at 24 hr, 8, 18, and 36 months post‐partum. Data are presented on the outcome of 519 children at age 3. At 3 years, children who were exposed prenatally to alcohol were smaller in weight, length, and head circumference. They also had an increased number of minor physical anomalies. These effects were found even after controlling for nutritional and environmental factors. The persistence of growth effects at age 3 suggests that children exposed to alcohol prenatally may have a diminished capacity for growth.