bluuebunny/crossref_metadata_2025 huggingface dataset:
Initial Sensitivity and Tolerance to Ethanol in Mice Genetically Selected for Diazepam Sensitivity
Authors: Gallaher Edward J. , Gionet Susanne E.
Published: April 2006

The benzodiazepine (BZ) receptor is coupled with a GABA‐receptor chloride‐ionophore complex. The BZs augment the GABA‐induced increase in chloride conductance, which leads to postsynaptic inhibition. This effect is believed to be responsible for antianxiety, sedative, muscle relaxant, and anticonvulsant effects, but the mechanisms underlying these behavioral effects are poorly understood. Various other sedative‐hypnotics, including ethanol and barbiturates, interact with this system, probably contributing to their behavioral effects. We have recently conducted a selective breeding program to develop lines of mice which are diazepam‐resistant (DR) and sensitive (DS) (Gallaher EJ, Hollister LE, Gionet SE, Crabbe JC. Psychopharmacology, 93:25–30, 1987); when tested for the duration of rotarod impairment after 20 mg/kg diazepam the DR line was impaired for 71 ± 13 min compared with 200 ± 18 min in the DS line. In the current study we tested mice from the DR and DS lines to determine if BZ sensitivity generalized to ethanol. DS mice became ataxic with lower brain ethanol concentrations, and recovered at later times and with lower blood ethanol concentrations, than did DR mice, indicating that sensitivity differences did extend to ethanol. Following a series of sequential doses over 5 to 6 hr DS mice developed minimal rapid tolerance, whereas DR mice developed considerable tolerance. By the end of the day DS mice were therefore much more sensitive to ethanol than were DR mice; this difference was greater in males than in females. High dose ethanol toxicity was studied by assaying brain ethanol concentrations at the cessation of respiration; no differences were found between lines or sexes.
Effects of Ethanol in Vivo and in Vitro on Stimulated Phosphoinositide Hydrolysis in Rat Cortex and Cerebellum
Authors: Gonzales Rueben A. , Crews Fulton T.
Published: April 2006

The effects of ethanol on phosphoinositide (PI) hydrolysis in rat cortex and cerebellum were studied to determine if this signal transduction mechanism is a pharmacological site of action for ethanol. In addition PI responses in young adult (8 months old) and old (22 months old) rats were compared to investigate the possible interaction between chronic ethanol treatment and aging on stimulated inositide metabolism. Fischer 344 rats were maintained on a nutritionally complete liquid diet containing sucrose or et hanol for 5 months. PI hydrolysis in prelabeled cortical or cerebellar slices was determined by measuring the release of [3H]inositol phosphates in the presence of 8 mM LiCI. Neither chronic ethanol nor aging altered maximal PI responses to carbachol or submaximal responses elicited by 20 mM KCI or 30 μM A23187. The glutamate‐induced response was slightly reduced in the aged rats. Concentration‐effect curves for norepinephrine (NE)‐stimulated PI hydrolysis were similar in sucrose‐ and ethanol‐treated cortex and cerebellum. Ethanol in vitro inhibited NE‐stimulated PI hydrolysis in cortical but not cerebellar slices. The ethanol‐induced inhibition of the NE‐stimulated PI response was not altered by aging or chronic ethanol treatment. These results suggest that aging or chronic ethanol treatment do not cause large changes in the responsiveness of most PI‐linked receptors, and thus, any deficits caused by these conditions may not be due to functional changes in receptor‐mediated PI hydrolysis.
Motor Performance in Detoxified Alcoholics
Authors: York James L. , Biederman Irving
Published: April 2006

Detoxified male and female alcoholics (aged 20–49 years) and agematched controls performed a series of 15–8ec target‐tapping tasks in which they alternatively marked two target strips with a felt marker as rapidly and as accurately as possible. Consistent with ‘Fitts’ Law (Fitts PM: J Exp Psych 47981–391, 1954), a highly linear relationship between movement time and task difficulty was observed in all four groups. Overall, the alcohdis were slower and made more errors than the controls, although the pattern of deficit differed for males and females. Accuracy, but not speed, was impaired in male alcoholics. The production of undershoot errors was increased more in alcoholics than nonalcoholics in targets of narrower width, whereas the production of overshoot errors was increased more in alcoholics as target separation decreased. Female alcoholics displayed impairment in speed of movement, but not accuracy. However, both alcoholic groups displayed elevated error rates for the more difficult targets. It is thus possible that detoxified alcoholics might mimic the speed functions of nonalcoholic individuals at the occasional cost of an erroneous response at a difficult target.
Ethanol‐induced Growth Inhibition: The Role of Cyclic AMP‐dependent Protein Kinase
Authors: Pennington Sam
Published: April 2006

Growth retardation is the single most common deficit observed in infants exposed to ethanol in utero, and the molecular mechanisms responsible for this growth inhibition are a focus of ongoing research. Several lines of research have suggested that ethanol‐induced changes in the adenylate cyclase‐protein kinase cascade may be involved in this process. Using an embryonic chick model, it was demonstrated that ethanol exposure during early development caused increases in cellular prostaglandin E2 and cyclic AMP levels that were inversely correlated with brain weight. Paradoxically, basal adenylate cyclase and protein kinase catalytic activities, assayed in vitro, were not altered by ethanol dosing. Ethanol exposure did suppress the responsiveness of brain adenylate cyclase to exogenous PGE2. Furthermore, ethanol treatment significantly lowered the brain cytoplasmic levels of cyclic AMP binding protein
Early Motor Development and Cerebral Cortical Morphology in Rats Exposed Perinatally to Alcohol
Authors: Norton Stata , Terranova Paul , Na Yol Joong , Sancho‐Tello Maria
Published: April 2006

Specific tests of early motor development and cerebral cortical morphology were studied in rats born from alcohol‐fed mothers, pair‐fed mothers, and ad libitum controls (either liquid or pellet diets). Liquid Bio‐Serv diets were used. Alcohol feeding began on day 5 of pregnancy and ended on day 10 postpartum. The weight gain of the pups after birth was drastically reduced compared with pair‐fed and other control groups; however, removal of the alcohol on day 10 postpartum resulted in an upswing of the growth curve that paralleled control groups. Between days 2 and 21 (postnatal) three behavioral tests of motor function were performed. Righting reflex (time for an animal to return to all four feet after being placed on its dorsum) was slightly delayed but the delay was not significant. Negative geotaxis time for an animal to rotate 180° from a head‐down position on an inclined plene), and reflex suspension (time an animal maintained its grip on a crossbar) were significantly delayed (˜2 days) in offspring from alcohol‐fed mothers. In the frontal cortex the offspring of alcohol‐treated mothers, a marked decrease (˜25%) in thickness of Lamina VI was found while the other Lamina (I‐V) were less altered. There results indicate that the effect of alcohol on the frontal cortex is related to a significant delay in motor development of reflex suspension and negative geotaxis since both of these require frontal integration.
Temporal Pattern of Alcohol Consumption in the United States
Authors: Arfken Cynthia L.
Published: April 2006

Alcohol is a major risk factor for many causes of injuries. A preliminary assessment at alcohol's involvement in specific causes of injuries must take into account when people are drinking. This study quantified the weekly and diurnal rhythm of alcohol consumption for the general U. S. population using data collected in a national survey. The data showed a strong temporal pattern consisting of more drinking on weekends with dally peaks in the early evening and troughs in the early morning. The national temporal drinking pattern was positively correlated (0.22 to 0.56) with national temporal patterns of motor vehicle accidents, a cause of injury commonly associated with drinking.
Detection and Localization of Immunoreactive Alcohol Dehydrogenase Protein in the Rat Testis
Authors: Yamauchi Masayoshi , Potter James J. , Mezey Esteban
Published: April 2006

Alcohol dehydrogenase in the testis metabolizes ethanol and a variety of physiological substrates such as dihydrotestosterone and vitamin A. Studies of the localization of enzyme activity in the testis have revealed its presence in either interstitial cells or seminiferous tubules alone or in both places. The purpose of this study was to detect and localize immunoreactive alcohol dehydrogenase in the testis. The testis enzyme had similar antigenicity than the liver enzyme as demonstrated by double immunodiffussion and inhibition titration using antibody to the liver enzyme. The concentration of immunoreactive enzyme protein was 1.7 ± 0.1 μg/mg of cytosol protein in the testis as compared with 9.3 ± 0.3 μg/mg of cytosol protein in the liver. Isoelectric focusing revealed eight isoenzyme bands. Only the three bands with the highest isoelectric points precipitated with antibody to liver alcohol dehydrogenase. By immunohistochemistry using this antibody, the enzyme was localized principally to the Leydig cells which are also the site of steroidogenesis. The presence in the seminiferous tubules of isoenzymes of lower isoelectric point, which do not react with the antibody to the liver enzyme, can not be excluded.
Effect of Ethanol Dose on Low density Lipoproteins and High Density Lipoprotein Subfractions
Authors: Hojnacki Jerome L. , Cluette‐Brown Joanne E. , Mulligan John J. , Hagan Stephanie M. , Mahony Kathleen E. , Witzgall Susan K. , Osmolski Thaddeus V. , Barboriak Joseph J.
Published: April 2006

Male squirrel monkeys were fed increasing caloric percentages (0, 12, 24, and 36%) of ethanol (ETOH) substituted isocalorically for carbohydrate as part of a chemically defined liquid diet to assess how alcohol dose modifies plasma lipoproteins and liver function. A separate group of primates was used to define the dose at which elevations in plasma apolipoprotein B first occurred and to measure plasma alcohol levels. ETOH caused a dose‐related, linear increase in high density lipoprotein (HDL) cholesterol which was primarily the result of increments in coronary protective HDL2 cholesterol. HDL2 total mass (lipid + protein) followed the pattern of HDL2 cholesterol. Animals fed the 12% regimen had plasma ETOH levels of approximately 49 mg/dl, the lowest low density lipoprotein (LDL) cholesterol, and the highest HDL2/HDL3 cholesterol ratio. Significant elevations in apolipoprotein B first appeared at 18% ETOH while higher doses (24 and 36%) caused increases in LDL cholesterol and HDL3, reduced HDL2/HDL3 ratios, and plasma alcohol levels of 142 and 202 mg/dl, respectively. Liver function tests were normal for all animals. Our results indicate that while a moderate ETOH caloric intake (12%) produces an antiatherogenic lipoprotein profile (↓ LDL/HDL, ↑ HDL2/ HDL3), any coronary protection afforded by continued increases in HDL2 at higher doses may be attenuated by concurrent atherogenic alterations (↑ LDL cholesterol, ↑ aplipoprotein B).
Impaired Lymphocyte Proliferative Response to Mitogen in Alcoholic Patients. Absence of a Relation to Liver Disease Activity
Authors: Mutchnick Milton G. , Lee Horchang H.
Published: April 2006

Concanavalin A‐induced lymphocyte proliferation was studied in 25 patients with alcoholic hepatitis or compensated alcoholic cirrhosis. Nine alcoholics without evidence of liver disease were also evaluated. A nonlinear correlation equation, which was natural logarithmic, was applied to individual dose‐response proliferation curves and permitted comparisons between patient groups and controls. The proliferative response in all patient groups was significantly lower when compared to healthy controls and was independent of the presence or absence of liver disease. This suggests that some changes in immune function observed in alcoholics may be linked to the direct effect of alcohol on the immune system rather than to the associated liver disease. This suggests that some changes in immune function observed in alcoholics may be linked to the direct effects of alcohol on the immune system rather than to the associated liver disease.
Chronic Alcohol Treatment Results in Disturbed Vitamin D Metabolism and Skeletal Abnormalities in Rats
Authors: Turner Russell T. , Aloia Roland C. , Segel Leigh D. , Hannon Kathleen S. , Bell Norman H.
Published: April 2006

The effect of chronic alcohol consumption on the skeleton was Investigated in rats. The treated group received ethanol administered as 38% of caloric intake in a liquid diet (Sustacal) for 10 months. The control rats were pair weighted to the ethanol‐treated animals throughout the study; the growth curves of the two groups were the same. The controls were given the same liquid diet except that dextrin: maltose (3:1) was substituted isocalorically for ethanol. Ethanol‐treated rats did not differ from the pair‐weighted controls in mean serum calcium, phosphorous, or creatinine. In contrast, serum magnesium was reduced (p < 0.02) in alcohol‐treated rats. Ethanol treatment also resulted in changes in the serum concentrations of vitamin D metabolites serum 1,25‐hydroxyvitamin D3 was increased (p < 0.001), while serum 1,25‐dihydroxyvitamin D3 was decreased (p < 0.01). Tibial length was reduced in ethanol‐treated rats (p < 0.05) but there was no change in femoral length. Medullary area was Increased in tibial diaphyses from alcohol‐treated rats compared to weight matched control animals (p < 0.01), indicating a net increase in resorption. The cross‐sectional area of the tibial diaphysis of ethanol‐treated rats was the same as the matched controls. Trabecular bone was decreased in the tibial metaphysis of ethanol‐treated rats compared to the matched controls (p < 0.05) indicating a net loss of trabecular bone. Ethanol treatment did not have an effect on the organic weight of the femur but the ash weight was reduced (p < 0.02). These studies demonstrate that chronic alcohol treatment in rats results in disturbed vitamin D metabolism, a net increase in bone resorption and decreased mineralization of bone matrix.
Accuracy of Death Certificates in the Diagnosis of Alcoholic Liver Cirrhosis
Authors: Blake J. E. , Compton K. V. , Schmidt W. , Orrego H.
Published: April 2006

In 108 patients with alcoholic liver disease who died during a 10‐year follow‐up, the diagnoses from the liver biopsies were compared with that from the Death Certificates. Data show that the currently used ICD‐9 category of cirrhosis with or without mention of alcohol has a 47.2% chance of missing the diagnosis of cirrhosis. On the other hand when the mention of liver disease in the Death Certificate is used for the diagnosis of cirrhosis, the percentage of undiagnosed cirrhosis decreases to 19.4% (p < 0.0001)
Observer Variation in Assessment of Liver Biopsies of Alcoholic Patients
Authors: Bedossa P. , Poynard T. , Naveau S. , Martin E. D. , Agostini H. , Chaput J. C.
Published: April 2006

The aim was to construct a questionnaire analyzing pathological features possibly present in alcoholic liver disease, to assess its interobserver variation and to determine the influence of technical data on this variation. A total of 764 inpatients drinking 90 g (median) of pure alcohol per day for 25 years was observed; 402 patients were excluded because of associated nonalcoholic disease, refusal or contraindication to biopsy, leaving 362 patients included. Two pathologists independently analyzed each biopsy and completed a questionnaire including 41 items. Coefficient of concordance between observers was evaluated with the kappa statistic (κ). The prevalence of 14 lesions was low, equal to or under 10%, leading to a nonsignificant concordance. For the 27 remaining features, two had an almost perfect degree of concordance (κ > 0.81): presence of hepatocellular carcinoma and cirrhosis. Three had a substantial coefficient of concordance (κ > 0.61): fibrous septa, size of cirrhotic nodules, and liver cell regeneration. Nine had a moderate (κ > 0.41), 11 a fair (κ > 0.21), and two a slight (κ < 0.21) coefficient of concordance. In terms of final diagnosis of alcoholic liver disease the concordance was substantial for cirrhosis with acute alcoholic hepatitis (κ= 0.77), cirrhosis without alcoholic hepatitis (κ= 0.75), acute alcoholic hepatitis without cirrhosis (κ= 0.65) and normal liver (κ= 0.64). Concordance was moderate for steatosis (κ= 0.47) and slight for fibrosis alone (κ= 0.16). For technical data, there was a trend for a higher concordance for the plastic‐embedded biopsies than for the paraffin‐embedded (p < 0.08) and for the samples containing more than six portal tracts than for the smaller biopsy samples (p < 0.10). In conclusion interobserver variations suggest that assessment of liver biopsies in alcoholic liver disease has to be carefully performed, in duplicate using clear definitions and a simplified questionnaire, for clinical research.
Effect of Chronic Ethanol Treatment and Selective Breeding for Hypnotic Sensitivity to Ethanol on Intracellular Ionized Calcium Concentrations in Synaptosomes
Authors: Daniell Laura C. , Adron Harris R.
Published: April 2006

The effect of chronic ethanol treatment and of selective breeding for hypnotic sensitivity to ethanol on intracellular ionized calcium concentrations (Ca1) were examined in mouse whole brain synaptosomes. Following treatment with a liquid diet for 7 days, resting Ca1 and KCl‐stimulated increases in Ca1 were measured in synaptosomes isolated from chronic ethanol‐treated and pair‐fed animals. Ethanol (350–700 mm) increased resting Ca1 and reduced KCl‐stimulated increases in Ca1 in synaptosomes isolated from pair‐fed animals. Ethanol‐induced changes in Ca1 were reduced in synaptosomes isolated from chronic ethanol‐treated animals. The effect of ethanol on synaptosomal Ca1 in long‐sleap (LS) and short‐sleep (SS) mice, selectively bred for differential sensitivity to the hypnotic actions of acute ethanol, was also investigated. In the absence of ethanol, resting values of Ca1 and KCl‐stimulated increases in Ca1 did not differ between the two lines of mice. Ethanol (200–000 mm) increased resting Ca1 and reduced depolarization‐stimulated increases in Ca1 in both long‐sleep and short‐sleep mice to the same degree. Similarly, KCl‐stimulated increases in Ca uptake did not differ in synaptotomes isolated from whole brains and cortices of LS and SS mice, in the absence or presence of ethanol. These findings demonstrate that tolerance develops to the effect of ethanol on neuronal Ca1 following chronic treatment. However, sensitivity to the hypnotic action of ethanol is not related to changes in neuronal Ca1 in LS and SS mice.
Validity of Self‐Report in Alcoholism Research: Results of a Veterans Administration Cooperative Study
Authors: Fuller Richard K. , Lee Kelvin K. , Gordis Enoch
Published: April 2006

The validity of self‐report in alcoholism treatment research is controversial. Our recently completed Veterans Administration Cooperative Study evaluating the efficacy of disulfiram treatment for alcoholism provided an opportunity to assess the validity of self‐report. To assess treatment response, patients and household contacts were interviewed at seven scheduled points during the 1 year of follow‐up. Blood specimens also were obtained from the patients at these times and were analyzed for ethanol. Urine specimens were collected from the patients when they returned for routine outpatient treatment visits and were analyzed for ethanol. Eighty‐eight percent of the patient and/or collateral interviews were obtained at 6 months and 90% at 1 year. The mean number of blood and urine specimens collected per patient was 4.3 and 14.4, respectively. Outcome criteria included continuous abstinence during the year and total number of drinking days. Continuous abstinence: If we had had only the patients' self reports, we would have significantly underestimated the percentage of men who drank. By self‐report 58.7% (355/605) relapsed whereas the combination of self report, collaterals' reports, and laboratory tests indicated that 72.4% (438/605) drank (p < 0.001). Using Bayes' theorem, the conditional probability that a patient is continuously abstinent for 1 year when he so claims is 65%. Total drinking days: Of the 213 patient‐collateral pairs each of whom provided all seven scheduled interviews, 46.9% (100/213) agreed on the total number of drinking days during the year. However, the collaterals were three times more likely to report more drinking days than the patients; 40.4% (86/213) of the cohabiting contacts reported more drinking days compared to 12.7% (27/213) of the patients reporting more drinking days (p < 0.001). Furthermore, the collaterals reported more total drinking days (86.2 ± 8.7) than the patients (61.6 ± 7.5, p= 0.033). We conclude that self‐report is not a valid method for measuring treatment response in alcoholism treatment studies.
Further Studies on the Neurochemical Mechanisms Mediating Differences in Ethanol Sensitivity in LS and SS Mice
Authors: French Thomas A. , Max Masserano Joseph , Weiner Norman
Published: April 2006

Long‐sleep (LS) and short‐sleep (SS) lines of mice were selectively bred for differences in CNS sensitivity to ethanol with LS mice exhibiting much greater sensitivity to hypnotic doses of ethand (4.0–4.5 g/kg) than SS mice. The influence of peripheral and central catecholamine neuronal systems on ethanol sensitivity (sleep time) In LS and SS mice was examined following administration of reserpine, α‐methyl‐p‐tyrosine and 6‐hydroxydopamine. Ten days after a single dose of reserpine, tyrosine hydroxylase activity was increased in the brain and adrenal gland of LS mice but only in the brain of SS mice dative to unbeated mice. Brain catecholamine levels in the reserpine‐treated mice were 25–50% lower in both LS and SS mice compared to levels in untreated mice. These changes were associated with a 41% reduction In LS sleep time, but a 90% increase in SS sleep time. SS mice were also more suspceptible to the lethal effects of reserpine. The increased mortality of SS mice may relate to a greater degree of reserpine‐induced hypothemia and a slower rate of recovery of brain catecholamine levels. Neonatal LS and SS mice treated with 6‐hydroxydopnmine exhibited increased levels of catecholamines in the locus cereleus, decreaaed levels in the cerebellum and unchanged levels in the hypothalamus at 60 days of age. These changes were associated with a modest decrease (10%) in LS sleep time and a marked increase (200%) in SS sleep time. α‐Methyl‐p–tyrosine decreased brain catecholamine levels of both lines by 30–50% while LS sleep times were unchanged and SS sleep times were increased by 45%. These contrasting alterations in ethanol sensitivity in LS and SS mice following alterations in the levels of tyrosine hydroxylase activity or catecholamines suggest that catecholamine neuronal systems are involved in the differential response to ethanol. The results further suggest that catecholamine systems may be Important in antagonizing the depressant effect of ethanol in SS mice, whereas catecholamine systems in LS mice may not be activated to a significant degree to neutralize the depressant actions of ethanol.
The HK/MBD Questionnaire: Replication and Validation of Distinct Factors in a Nonclinical Sample
Authors: Sher Kenneth J. , Alterman Arthur I.
Published: April 2006

Although Tarter et al.'s (1977) HK/MBD questionnaire has been found useful in subtyping populations of clinical alcoholics, its potential utility in nonclinical populations has yet to be determined. The current study examined the family history, personality, and substance use/abuse correlates of Tarter et al.'s HK/MBD questionnaire and factor‐analytically derived subscales (Alterman and McLellan, 1986) in a nonclinical sample of 580 young, adult males. In addition, a factor analysis of the HK/MBD questionnaire was undertaken to assess the extent to which the factor structure determined on a clinical alcoholic sample replicates in a nonclinical sample. Results indicated that each of the HK/MBD subscales showed relatively unique patterns of correlations with the various personality measures employed suggesting that they are measuring separate constructs. Perhaps of greatest importance, the HK/MBD items that appear to be of greatest relevance for understanding substance use/abuse are those related to antisocial behavior. Finally, the factor structure of the HK/MBD questionnaire in the nonclinical sample was found to be quite similar to the structure obtained in a clinical sample. These results demonstrate the multidimensional structure of the HK/MBD questionnaire and the utility of using the more homogeneous subscales in research with both clinical and nonclinical samples.
Recent International Reductions and Increases in Liver Cirrhosis Deaths
Authors: Smart Reginald G.
Published: April 2006

This paper examines changes in liver cirrhosis death rates in 29 countries between 1974 and 1983 or the latest year available. Seven countries show a decline in death rates, six an increase, and the mining 17 show no clear significant trends. Changes were more common among countries with high rates of alcohol consumption and high rates of liver cirrhosis deaths. Limited evidence for a widespread amelioration in liver cirrhosis seems to exist.
Lack of Prenatal Testosterone Surge in Fetal Rats Exposed to Alcohol: Alterations in Testicular Morphology and Physiology
Authors: McGivern Robert F. , Raum William J. , Salido Eduardo , Redei Eva
Published: April 2006

Pregnant Sprague‐Dawley rats were administered a liquid alcohol diet (35% ethanol‐derived calories), a pair‐fed isocaloric diet, or dry food pellets beginning on Day 14 of gestation and continuing until parturition. Testosterone levels in male fetuses were measured on Days 17 through 20 of gestation. The normal surge of testosterone on Days 18 and 19 was present in controls, but notably absent in male fetuses exposed to alcohol. Light microscopic examination of the testes at birth revealed a reduction in the number of leydig cells in the alcohol exposed group and the presence of a large number of vacuoles in the seminiferous tubules. In vitro studies of fetal testes at 18 and 22 days of gestation revealed that this in utero alcohol exposure regimen produced a marked insensitivity to rat LH (10 ng/ml) stimulation of testosterone secretion compared to controls. The response to ethanol (160 mg/dl) in alcohol exposed testes was characterized by a long‐lasting suppression of testosterone compared to a large increase observed in control testes. No differences in anogenital distance were observed among the groups. Together, these data may explain some of the long‐term feminizing and demasculinizing effects on reproductive and nonreproductive sexually dimorphic behaviors observed in adult males prenatally exposed to alcohol.
Noninvasive Estimation of Blood Alcohol Concentrations: Ethanol Vapor Above the Eye
Authors: Giles H. G. , Sandrin S. , Saldivia V. , Israel Y.
Published: April 2006

The present study describes, in animals, a novel approach to the in vivo, noninvasive determination of alcohol in the body. The concentration of ethanol in vapor above the lacrimal fluid in the eye was analyzed in situ by the use of a fast (1‐min) gas sensor method developed previously for biological liquids. After an oral dose of 1 g/kg to 11 animals, eye vapor measurements and blood samples were obtained over 4 hr. The correlation of 61 blood ethanol concentrations obtained by the two methods yielded a correlation coefficient of 0.92 and a slope of 0.99. The metabolic rates of ethanol determined by gas chromatographic analysis of blood and by ethanol eye vapor analysis are virtually identical. The data suggest that ethanol eye vapor analysis may be an attractive, noninvasive method for the determination of ethanol in animals. The method is not subject to false high readings due to alcohol in the buccal cavity and thus might constitute an alternative to breath analysis in the human.

In a separate series, ethanol was determined by head space gas chromatography in samples of blood and lacrimal fluid while the animals were under ketamine anesthesia. The correlation of ethanol concentrations in blood and lacrimal fluid (r = 0.99) shows that ethanol is distributed in lacrimal fluid which comprises part of total body water.
Paternal Alcohol Exposure Affects Offspring Behavior but not Body or Organ Weights in Mice
Authors: Abel Ernest L. , Lee Julia A.
Published: April 2006

Male mice consumed liquid alcohol diets containing 20, 10, or 0% ethanol‐derived calories (EDC) for 56‐61 days. Animals fed the 10 and 0% EDC diets were pair‐fed to 20% EDC animals. A nontreated ad libitum group was included to assess the effects of pair‐feeding. After treatment, males were bred to nontreated females.

Litter size, birthweight, bodyweight at 21 or 55 days of age, and organ weights except for thymus were not affected by paternal alcohol ingestion. There was a dose‐related decrease in activity at 20 and 24 days of age in an activity chamber and a dose‐related decrease in serum testosterone levels at 55 days of age in male offspring sired by alcohol‐consuming males. Offspring sired by males consuming the 20% EDC diet also required fewer trials to learn a passive avoidance task and had longer latencies to reach the choice point in a T maze.
Use of an Objective Clinical Scale in the Assessment and Management of Alcohol Withdrawal in a Large General Hospital
Authors: Foy Aidan , March Susan , Drinkwater Vine
Published: April 2006

A modified version of the Clinical Institute Withdrawal Assessment Scale (CIWA) was used in the management of alcohol withdrawal in a general hospital. Patients who developed seizures or confusion were noted to score higher on the scale, even before these complications, than patients who remained uncomplicated (21.7 ± 1.2 compared to 15.6 ± 0.55).

When the score was used as a guide for treatment, it was found that patients scoring >15 were at significantly increased risk of severe alcohol withdrawal if they remained untreated (RR, 3.72; 95% confidence interval, 2.85‐4.85). The higher the score the greater this relative risk. Some patients however, still suffered complicated withdrawals although their scores were low or they were apparently adequately treated.

It is concluded that the use of an objective clinical scale of alcohol withdrawal is valuable in a general hospital to identify those patients in early withdrawal who need sedation to avoid complication. There will however, be a small group of patients whose clinical course will be difficult to predict and further work is needed to determine the reasons for this.
Event‐related Brain Potentials in Individuals at High and Low Risk for Developing Alcoholism: Failure to Replicate
Authors: Polich John , Bloom Floyd E.
Published: April 2006

Event‐related brain potentials (ERPs) were used to compare young men having a positive paternal family history for alcoholism (FHP) with carefully matched control subjects having no family history for alcoholism (FHN). The P300 ERP component was obtained from all subjects (n= 10/group) with a complex auditory paradigm before and on two occasions after they received a placebo drink which they were told might contain alcohol. The procedures employed replicated those of a previous study1 in which FHP subjects showed diminished P300 potentials compared to FHN subjects under the placebo as well as ethanol consumption conditions—a finding which raised the possibility that the P300 ERP component might be a biological marker for subjects at high risk to develop alcoholism. No differences between the family history groups were obtained for the P300 or any other ERP component using the replication procedures. Both groups demonstrated a decrease in P300 amplitude across trial blocks in a similar fashion suggesting that habituation effects may have diminished the ERP response.
Impact of Depressive Symptomatology on Alcohol Problems in Women
Authors: Turnbull Joanne E. , Gornberg Edith S. L.
Published: April 2006

The association between the amount of depression manifest at time of an alcoholic woman's admission to treatment, the course of alcoholism and its consequences, and early psychosocial vulnerabilities was examined in a sample of women in treatment for alcoholism (n= 301). Two indices of depression, one reflecting low self‐esteem and the other current mood were constructed by factor analysis of interview items measuring depression (drawn from Center for Epidemiological Studies Depression scale, Diagnostic Interview Scale, and Personal Attributes Questionnaire). Both depression indices were associated with earlier age of onset and earlier loss of control. Binge drinking was associated with current mood, while daily/weekend drinking was associated with low self‐esteem. Both measures were associated with the consequences of alcoholism. An examination of alcoholic women's background revealed that there are some influences in the early family environment that are associated with increased levels of depression in alcoholic women.
The Preoccupation with Alcohol Scale: Development and Validation
Authors: Leonard Kenneth E. , Harwood Margaret K. , Blane Howard T.
Published: April 2006

The purpose of the present study was to develop a psychometrically sound measure of preoccupation with alcohol in a group of young, heavy drinking men and to examine some correlates of this drinking style. A brief Preoccupation with Alcohol Scale (PAS) was derived that exhibited substantial internal consistency. Data from a sample of the 67 males indicated that higher PAS scores were significantly related to alcohol consumption and frequency of intoxication within many different contextual circumstances. The PAS was also related to alcohol problems after controlling for average daily alcohol consumption and frequency of intoxication, suggesting that scores on the PAS are related to, but not redundant with, level of alcohol consumption. Results from a cross‐validation sample provided additional support for these findings. The authors suggest that a preoccupation with alcohol may be a cognitive‐behavioral risk factor for the development of severe alcohol problems and alcoholism.
Role of Alcohol‐induced Hypothermia in Mediating the Teratogenic Effects of Alcohol in C57BL/6 J Mice
Authors: Randall Carrie L. , Anton Raymond F. , Becker Howard C.
Published: April 2006

The purpose of this study was to determine the role of alcohol‐induced maternal hypothermia in the teratogenic actions of alcohol. C57BL/6J mice were administered an acute dose of alcohol (5.8 g/ kg orally) or isocaloric sucrose on day 10 of gestation. One half of each group was placed for 6 hr in an incubator set at 32°C and the other half was housed in the incubator at room temperature (22°C). As expected, acute prenatal alcohol exposure at this time of gestation was associated with decreased birth weight and an increase in limb and kidney malformations. The significant alcohol × environmental temperature interaction on these dependent variables indicated that the teratogenic insult was not attenuated, but was in fact even greater for the 32°C/alcohol group. An absence of a main effect of environmental temperature indicated that the 32°C environment, per se, was not teratogenic. Thus, maternal hypothermia is probably not an etiological factor in animal models of fetal alcohol syndrome. Moreover, antagonism of alcohol‐induced maternal hypothermia exacerbates the teratogenic actions of alcohol observed at room temperature.
Changes in Erythrocyte Enzyme Activities during Erythrocyte Aging in Alcoholism
Authors: Mezey Esteban , Rhodes Deborah L.
Published: April 2006

Aldehyde dehydrogenase, glucose‐6‐phosphate dehydrogenase, and pyruvate kinase activities were determined in erythrocytes of various ages, separated by Percoll gradient centrifugation, in 13 alcoholic patients and eight control subjects. The total erythrocyte activities of all three enzymes were not affected by alcoholism, however, the youngest cells of alcoholics had a decreased aldehyde dehydrogenase activity, while both glucose‐6‐phosphate dehydrogenase and pyruvate kinase activities were increased. The depression of aldehyde dehydrogenase activity not only persisted, but became more marked after 2 weeks of abstinence, while the enhanced activities of the two other enzymes returned to normal. These observations suggest that chronic alcohol ingestion suppresses aldehyde dehydrogenase in the bone marrow, while it enhances other erythrocytic enzymes.
Effect of Prenatal Exposure to Ethanol on the Development of Cerebral Cortex: I. Neuronal Generation
Authors: Miller Michael W.
Published: April 2006

Prenatal exposure to ethanol causes profound disruptions in the development of the cerebral cortex. Therefore, the effect of in utero ethanol exposure on the generation of neurons was determined. Pregnant rats were fed a liquid diet in which ethanol constituted 37.5% of the total caloric content (Et) or pair‐fed an isocaloric control diet (Ct) from gestational day (GD) 6 to the day of birth. The time of origin of cortical neurons was determined in the mature pups of females injected with [3H]thymidine on one day during the period from GD 10 to the day of birth. The brains were processed by standard autoradiographic techniques.

Ethanol exposure produced multiple defects in neuronal ontogeny. The period of generation was 1‐2 days later for Et‐treated rats than for rats exposed prenatally to either control diet. Moreover, the generation period was 1‐2 days longer in Et‐treated rats. The numbers of neurons generated on a specific day was altered: from GD 12‐19 significantly fewer neurons were generated in Et‐treated rats than in Ct‐treated rats, whereas after GD 19 more neurons were born. The distribution of neurons generated on a specific day was disrupted; most notable was the distribution of late‐generated neurons in deep cortex of Et‐treated rats rather than in superficial cortex as they are in controls. Cortical neurons in Et‐treated rats tended to be smaller than in Ct‐treated rats, particularly early generated neurons in deep cortex. The late‐generated neurons in Et‐treated rats were of similar size to those in Ct‐treated rats despite their abnormal position in deep cortex. Neurons in Ct‐treated rats tended to be rounder than those in Et‐treated rats which were more polarized in the radial orientation. A proliferation index, which was based on the amount of autoradiographic signal over each labeled neuron, indicated that an additional, late surge in proliferative activity occurred in Et‐treated rats on GD 20‐21. The amount of [3H]thymidine incorporated each day was determined by biochemical analyses. In Ct‐treated rats, incorporation increased to a maximum on GD 17 and decreased thereafter. In Et‐treated rats, there were two maxima, the first on GD 18 and the second on GD 20. These data fully support the findings of the autoradiographic analyses.

The present data show that neuronal generation is profoundly affected by ethanol. Such disturbances result from ethanol‐induced abnormalities in neuronal proliferation and migration.
4‐Methylpyrazole: A Controlled Study of Safety in Healthy Human Subjects after Single, Ascending Doses
Authors: Jacobsen Dag , Sebastian C. Simon , Blomstrand Rolf , McMartin Kenneth E.
Published: April 2006

4‐Methylpyrazole (4‐MP), an inhibitor of alcohol dehydrogenase, is a possible future drug for the treatment of methanol and ethylene glycol intoxications and the severe ethanol‐disulfiram reaction. Therefore a placebo‐controlled, double‐blind, single‐dose, randomized, sequential, ascending‐dose “Phase I study” was performed in healthy volunteers in order to determine the tolerance of 4‐MP at dose levels of 10 (n= 4), 20 (n= 4), 50 (n= 4), and 100 mg/kg (n= 3). Along with each dose group, there were two placebos except with the 100 mg/kg group where there was only one placebo. In the 10 and 20 mg/kg group there were no side‐effects in any subject. At the 50 mg/kg level, three out of four subjects experienced slight to moderate nausea and dizziness from 0 to 2.5 h after dosing. In the 100 mg/kg group all three subjects reported side‐effects like nausea, dizziness, and vertigo, that were short‐lived in two subjects, but lasted up to 30 h in one subject The study was stopped after evaluation of the latter subject, so fewer subjects were completed in this last group. Despite these subjective side‐effects, there were no significant changes in objective clinical parameters like pulse, blood pressure, body temperature, or blood and urine chemistries. We conclude that at a single dose of 4‐MP (10–20 mg/kg) producing plasma levels within a probable therapeutic range, no side‐effects were attributed to 4‐MP.
Tolerance to Ethanol and Cross‐Tolerance to Pentobarbital by Isolated Hearts from Chronic Alcoholic Rats
Authors: Segel Leigh D.
Published: April 2006

The effects of ethanol and pentobarbital on the function of isolated working hearts from control and ethanol‐fed male Long‐Evans rats were studied. Hearts from ethanol‐fed animals (38% of calories; 10–12 months) exhibited functional tolerance to the cardiodepressive effects of 18–71 mM ethanol in the perfusing medium. Lett ventricular systolic pressure, peak relaxation rate, isovolumic pressure indexes, peak aortic flow rate, cardiac output, and stroke work of the control hearts were depressed to a greater extent than were those indexes of the alcoholic rat hearts during exposure to ethanol in vitro. Differences in the functional responses of controls and alcoholics were not the result of differences in energetics; myocardial O2 consumption, O2 supply‐to‐utilization ratio, and external work efficiency changed similarly in both groups of hearts during perfusion with ethanol. Cross‐tolerance of the alcoholic rat hearts to the in vitro cardiodepressive effects of pentobarbital was also apparent. Peak rate of left ventricular pressure development, peak aortic flow rate, isovolumic pressure indexes, and cardiac output of the control rat hearts were significantly lower than those indexes of the alcoholic rat hearts during perfusion with 0.5 MM pentobarbital. In addition, four of the seven control hearts could not be paced during pentobarbital perfusion using 3V electrical pulses; the pacing voltage had to be raised and right ventricular pacing used to maintain stable function of those hearts at a 321 beats/min pacing rate. Myocardial O2 consumption and O2 supply‐to‐utilization ratios of control and alcoholic rat hearts were similar, but external work efficiency was slightly higher in the alcoholics than in controls during pentobarbital perfusion. The data indicate that chronic ethanol consumption confers tolerance to ethanol and cross‐tolerance to pentobarbital which can be detected in whole heart function in an in vitro setting.
Dietary Tryptophan Reverses Alcohol‐induced Impairment of Facial Recognition But Not Verbal Recall
Authors: Westrick Edward R. , Shapiro Allan P. , Nathan Peter E. , Brick John
Published: April 2006

The present study demonstrates that alcohol‐induced memory impairment can be attenuated by pretreatment with an oral tryptophan supplementation. These results provide support for the role of a brain serotonin deficit in this impairment and highlight the impact a dietary manipulation can have on a complex behavioral process.
Disturbances in Na+ Transport Systems Induced by Ethanol in Human Red Blood Cells
Authors: Coca Antonio , Garay Ricardo
Published: April 2006

The effects of ethanol on fluxes catalyzed by four Na+ transport systems (ouabain‐sensitive Na+, K+ pump, bumetanide‐sensitive Na+, K+ cotransport system, Na+:Li+‐ countertransport and anion carrier) and on Na+ and K+ leaks were investigated in human red blood cells.

Ethanol concentrations higher than 32 my were required in order to significantly modify erythrocyte Na+ transport function. The observed changes can be summarized as follows: (a) stimulation of Na+ efflux through the Na+, K+ pump (by 21–32% at 160–400 mm) and Na+:Li+ countertransport (by 34–59% at 160–400 mmk (b) inhibition of outward Na+, K+ cotransport (by 23–34% at 160–400 mm) and LiCO3‐ influx through the anion carrier (by 17–21% at 64–400 mm); and (c) increase in Na+ and K+ leaks (by 13–16% at 64–400 mm).

The effects of ethanol on the Na+, K+ pump and Na+, K+ cotransport system resulted from changes in maximal rates of Na+ efflux (increased and decreased, respectively) without any significant effect on the apparent affinities for internal Na+.

Erythrocytes preincubated for 1 hr with 160 mm ethanol, washed and further incubated in flux media, recovered a normal Na+ transport function.

In conclusion, high concentrations of ethanol induced reversible perturbations of fluxes catalyzed by erythrocyte Na+ transport systems. The observed effects may reflect disturbances in Na+ transport function associated with severe intoxication.
Impact of Cirrhosis on the Neuropsychological Test Performance of Alcoholics
Authors: Tarter Ralph E. , Van Thiel David H. , Arria Amelia M. , Carra Joseph , Moss Howard
Published: April 2006

Alcoholics and nonalcoholics with biopsy‐proven cirrhosis were compared to each other and to a normal control group on a comprehensive battery of neuropsychological tests. No systematic differences were found between the two liver disease groups. These results indicate that a history of alcoholism does not substantially contribute to the manifest neuropsychological deficits beyond that due to a coexistent hepatic encephalopathy.
Plasma Carnitine in Alcoholism
Authors: Fuller Richard K. , Hoppel Charles L.
Published: April 2006

Carnitine is essential for the β‐oxidation of long‐chain fatty acids in the mitochondria and probably has a major role in modulating the acyl‐coenzyme A/reduced coenzyme A ratio in the matrix of mitochondria. Plasma carnitine concentrations are elevated in several conditions and reflect changes at the cellular level. We previously had reported elevated plasma carnitine in patients with alcoholic liver disease compared to healthy control subjects. In this study we measured plasma carnitine in a third group, alcoholic patients without overt liver disease. The alcoholic patients (n=20) had significantly elevated plasma long‐chain acylcarnitine (P<0.01) compared to 32 healthy men of identical age and significantly lower short‐chain (P<0.01) and long‐chain acylcarnitine (P<0.01) than 28 men with alcoholic liver disease. We conclude that alcoholism is another condition in which carnitine homeostasis is altered.
Effect of L‐Carnitine on Ethanol and Acetate Plasma Levels after Oral Administration of Ethanol in Humans
Authors: Adamo S. , Siliprandi N. , Dl Lisa F. , Carrara M. , Azzurro M. , Sartori G. , Vita G. , Ghidini O.
Published: April 2006

In a randomized double‐blind, cross‐over experiment, 0.5 g/kg of ethanol in the form of white wine and 3 g of L‐carnitine by intravenous infusion were administered to 15 healthy volunteers. Ethanol and acetate plasma levels and the urine concentrations of acetylcarnitine were determined. Administration of ethanol induced a significant increase of both plasma ethanol and acetate, lasting 6–8 hr. The concomitant administration of carnitine resulted in a significant decrease of plasma acetate, whereas plasma ethanol levels remained unmodified. Urinary acetylcarnitine content significantly increased following administration of ethanol plus carnitine, but not when L‐carnitine alone was administered. The resulting conclusion is that administered L‐carnitine might trap excess acetyls derived both from free acetate, formed by ethanol oxidation, and from acetyl coenzyme A, accumulated as a result of the ethanol‐induced decrease in the Krebs cycle flux.