bluuebunny/crossref_metadata_2025 huggingface dataset:
Altered Sleep Physiology in Chronic Alcoholics: Reversal with Abstinence
Authors: Williams Harold L. , Rundell O. H.
Published: February 2008

Somnograms obtained from recently abstinent chronic alcoholics reveal gross disruption succinctly described as “fractured” sleep. Sleep onset is delayed and the rhythmic properties of the sleep pattern are markedly disturbed with numerous brief arousals and changes of sleep stage. Excessive stage 1 and stage rapid eye movement sleep are present while the high voltage slow wave sleep is markedly reduced or absent. With continued sobriety (9 mo or more) the sleep stage percentages tend to return to normal levels, but the disruption of the sleep pattern persists after as much as 21 mo of abstinence.
Common Genetic Mechanisms in Alcoholism and Psychiatric Disorders: Negative Evidence From a Study of Ethnic Group Patients
Authors: Galdi Joe , Bonato Roland R.
Published: February 2008

Alcoholism in the male relatives of patients with various (nonalcoholic) psychiatric disorders is consistently elevated above population risk. Over the years, this finding has given rise to theories which propose that some forms of alcoholism are attributable to the pleiotropic expression of genes underlying these disorders. This mechanism was tested in the fathers of patients from ethnic groups associated with culturally suppressed alcohol abuse where it was predicted that decreased alcoholism would be substituted for by increased psychiatric disorder. Results, however, failed to support such a mechanism. Other explanations of this elevated alcoholism were considered.
Specific Memory Deficits Associated with Prolonged Alcohol Abuse
Authors: Riege Walter H. , Holloway Judith A. , Kaplan David W.
Published: February 2008

The relationship between age, education, length and amount of heavy drinking, and performance on five memory tasks was investigated in 54 chronic alcoholics and 18 age‐matched controls. Alcoholics with less than 12 yr of heavy drinking differed reliably from long‐term (13–22 yr) and extended long‐term drinkers (>23 yr) in recognition memory for visual patterns when scores were corrected for age. Compared with controls, both groups of long‐term drinkers were deficient on the visual, auditory, and Faces recognition tests. Age and education of alcoholics accounted for part of performance differences; length of alcohol abuse, however, predicted reliably the decline in memory scores on all but the tactual test. The profile of memory performances seemed to decrease linearly with increasing age and length of alcohol abuse.
Comparison of Clients Completing Inpatient Alcoholism Treatment with Clients Who Left Prematurely
Authors: Welte John W. , Hynes Gerard , Sokolow Lloyd , Lyons Joseph P.
Published: February 2008

Those clients who completed inpatient alcoholism treatment are shown to have a better outcome than those who dropped out or were terminated, even after correcting for poorer original prognosis. Financial status, time since last employment, social stability, and age prove to be significant predictors of reason for leaving treatment.
Properties of Cerebral Polyribosomes and Membranes of the Rough Endoplasmic Reticulum after Ethanol Dependence in Rats
Authors: Fleming Eugene W. , Tewari Sujata
Published: February 2008

Effects of physical dependence upon ethanol on the polyribosomal properties and the reconstitution of the rough endoplasmic reticulum (RER) of the brain has been examined. The purified free polyribosomes (polysomes), membrane‐bound polysomes, and a fraction of RER membrane that has been stripped of polysomes were isolated from rat brain. RNA yields, amino acid incorporation activities, and electron micrographs established the purity of stripped membranes, but no differences were detected following the ethanol treatment. For the polyribosomal fractions, the stability of the mRNA/ribosomal complex was decreased after ethanol dependence as was the in vitro translation of endogenous mRNA. In the reconstitution reaction, the incubation of membranes from ethanol‐treated animals with either source of purified bound polysomes resulted in higher yields of protein than when control membranes were used. The above results suggest that ethanol dependence affects the properties of both the RNA and membrane components of the RER of brain.
Lipid Peroxidation in Alcoholic Liver Disease in Humans
Authors: Suematsu Toshihiko , Matsumura Takakatsu , Sato Nobuhiro , Miyamoto Takashi , Ooka Teruji , Kamada Takenobu , Abe Hiroshi
Published: February 2008

The lipoperoxide level in liver as well as serum in alcoholic patients was measured by using the thiobar‐bituric acid method. Heavy drinkers with deposition of fat in liver had a significantly (p < 0.001) higher level of hepatic lipoperoxide examined in about 7 days after abstinence than did nonalcoholic individuals with histologically normal liver. Of these heavy drinkers, cases with a remarkably high level of liver lipoperoxide showed a high incidence of hepatic cell necrosis. The hepatic lipoperoxide level was correlated with the serum lipoperoxide level in these heavy drinkers (r = 0.750, p < 0.001). In chronic alcoholics, high levels of serum lipoperoxide were usually observed on admission, and a significant positive correlation was found between the serum lipoperoxide level and serum GOT activity (r – 0.541, p < 0.01). After a 2‐wk abstinence, the levels of serum lipoperoxide decreased, which was associated with improvement of liver function tests. These results suggest a possible involvement of lipid peroxidation in alcohol‐induced liver damage in humans.
Cerebrospinal Fluid GABA and Cyclic Nucleotides in Alcoholics with and without Seizures
Authors: Goldman Gerald D. , Volicer Ladislav , Gold Barry I. , Roth Robert H.
Published: February 2008

Cerebrospinal fluid levels of r‐aminobutyric acid (GABA) and cyclic nucleotides were measured in alcoholic and control patients. Alcoholics without seizures had higher GABA levels than either alcoholics with seizures or controls. Levels of cyclic AMP and cyclic GMP in cerebrospinal fluid of controls and alcoholics with and without seizures were not significantly different.
Association of Cerebral Infarction and Chronic Alcoholism: An Autopsy Study
Authors: Walbran Bonnie B. , Nelson James S. , Taylor John R.
Published: February 2008

Central nervous system (CNS) infarcts were present at autopsy in 10 of 23 alcoholic patients and in 9 of 36 nonalcoholic patients. There were more males than expected in the infarct population and in the alcoholic population. Male subjects comprised the entire population of alcoholics with infarcts. In addition, a history of alcohol abuse was present in every case of cerebral infarction dying before age 75. The incidence of cardiomegaly was increased among the alcoholics. There were no differences between alcoholics and nonalcoholics in the incidence of diagnosed hypertension, moderate‐to‐severe coronary atherosclerosis, or adult onset diabetes. However, CNS infarction was more likely to occur at an earlier age in alcoholics than in nonalcoholics. Excessive alcohol consumption may be a risk factor in the premature development of cerebrovascular disease in males.
Utilization of Medical Services by Alcoholics Participating in a Health Maintenance Organization Outpatient Treatment Program: Three‐Year Follow‐Up
Authors: Reiff Sidney , Griffiths Barbara , Forsythe Alan B. , Sherman Richard M.
Published: February 2008

In a cumulative 3‐yr follow‐up study of utilization of medical services by alcoholics participating in a health insurance maintenance organization (HMO) outpatient alcoholism treatment program, expenditures of 59 alcoholics were compared with those of 78 alcoholics who chose not to participate. Results show significant differences in dollar cost per patient per year between groups in inpatient expenditures (p = 0.03). When alcoholism clinic costs were excluded from combined inpatient and outpatient expenditures, significance was maintained over the 3 yr (p = 0.02). In combined inpatient and outpatient expenditures including alcoholism treatment costs, the dollar differential between groups was substantial but not statistically significant.
The Effect of Chronic Poisoning with Carbon Tetrachloride on Voluntary Consumption of Ethanol by Mice
Authors: Dole Vincent P. , Gentry R. Thomas , Ho Ann
Published: February 2008

Mice were chronically poisoned with carbon tetrachloride injected twice weekly, intraperftoneally, in doses of 0.05‐0.80 mg/g over 10 to 16 weeks. The poisoned animals, as compared to vehicle‐injected controls, showed marginally significant increases in voluntary consumption of ethanol in a three‐bottle choice (water, 10% and 20% ethanol continuously available), but not to a degree that could be considered alcoholic. The average daily intakes of ethanol remained within the range of variation for normal animals of this strain; there was no consistent shift in preference from 10% to 20% ethanol, and the distribution of drinking times within the 24‐hour cycle remained normal. The relevance of these findings to the clinical problem of alcoholism is that the appetite for alcohol, a potential hepatotoxin, persists despite serious damage to the liver.
The Adverse Effects of Ethanol upon Hypothalamic‐Pituitary‐Gonadal Function in Males and Females Compared and Contrasted
Authors: Thiel David H. Van , Gavaler Judith S.
Published: February 2008

The similarities and differences in the adverse effects of ethanol upon hypothalamic‐pituitary‐gonadal function of males and females are compared and contrasted. In addition, adverse effects upon gametes and the developing fetus are discussed.
Mechanism of Ethanol‐Induced Adrenal Stimulation
Authors: Cobb Charles F. , Thiel David H. Van
Published: February 2008

A historical review of studies addressing the adrenal cortical response to ethanol and the mechanisms thought to contribute to such responses is presented. Studies reviewed range from the earliest based upon crude bioassay techniques to more modern papers which have utilized highly specific radioimmunoassay techniques and isolated perfused rat adrenal glands. Evidence for both hypothalamic‐pituitary as well as direct adrenal stimulation is presented. Available evidence, however, would suggest that acetaldehyde rather than ethanol per se, is responsible for direct adrenal stimulation when it occurs.
Blood Pressure and Alcohol Intake in Heart Patients
Authors: Barboriak Peter N. , Anderson Alfred J. , Hoffmann Raymond G. , Barboriak Joseph J.
Published: February 2008

The association between alcohol consumption and blood pressure has been studied in 2025 male and 282 female patients undergoing diagnostic coronary angiography. The increase in amount of alcohol consumed correlated with higher systolic and diastolic blood pressure; this effect was especially pronounced in men over 50 years of age. The association was less marked in male patients under 50 years old, in women, and in patients on antihypertensive medication. Readings in the range of definitive hypertension were more prevalent among older patients consuming six or more drinks daily than in abstainers of the same age group.
The In Vivo Metabolism of Tertiary Butanol by Adult Rats
Authors: Baker Rodney C. , Sorensen Stephen M. , Deitrich Richard A.
Published: February 2008

The metabolism of tertiary butanol has been considered to be limited to direct conjugation of the hydroxyl group. Therefore, the alcohol has been used to differentiate between the direct effects of ethanol and those caused by metabolism or metabolic products of ethanol. The in vitro oxidation of tertiary butanol has been reported, and in this report we describe the in vivo oxidation of tertiary butanol. Radiolabeled and stable isotope‐labeled acetone was recovered from animals treated with corresponding labeled t‐butanol. 14CO2 was also recovered from animals treated with [14C]t‐butanol.
Elevation of the Hemoglobin Al Fraction in Alcoholism
Authors: Hoberman Henry D. , Chiodo Sandra M.
Published: February 2008

The proportion of hemoglobin A1 was measured in 43 normoglycemic men and women admitted consecutively to an alcohol treatment center and in 41 healthy volunteers. On the average, the size of the fraction was significantly greater in the alcoholic patients than in the healthy subjects. The results of hemoglobin A1c determinations added independent evidence that this difference was not due to formation of any of the known glycosylated hemoglobins despite the fact that the alcohol‐related hemoglobin was found to cochromatograph with hemoglobin A1 c.

The size of the hemoglobin A1 fraction was unrelated to the presence or absence of alcoholic hepatitis, although most patients having abnormally high serum hepatic enzyme activities were also found to have abnormal elevations of the A1 fraction. However, some patients with normal serum enzyme activities were among those having the highest values of the A1 fraction, indicating that the latter was a more sensitive indicator of excessive alcohol intake than were hepatic enzyme activities.

The proportion of hemoglobin A1 in a patient followed over a period of 9 months rose to a maximum as the patient continued to drink. In a patient who abstained from drinking while under hospital care, the A1 fraction decreased towards normal with a half‐time of 11 days. These observations are interpreted as evidence that alcohol‐related hemoglobin is a product of a readily reversible reaction occurring at a maximal rate of 0.038 mm day‐1, about 4 times as rapid as is the formation of hemoglobin A1c.
Variation in Alcoholism Treatment Orientation: Differential Impact upon Specific Subpopulations
Authors: Lyons Joseph P. , Welte John W. , Brown Joseph , Sokolow Lloyd , Hynes Gerard
Published: February 2008

Treatment programs across the State of New York were studied to determine the differential impact of treatment orientations upon various types of alcoholism clients. 1340 patients from 17 alcoholism treatment programs were treated and followed up 3 and 8 months after treatment. The majority of the clients were categorized as either Behaviorally Impaired Drinkers (n=205) or Alcoholics (n = 814). Each of the treatment programs were classified according to either Peer Group, Rehabilitation Professional, or Medical Orientations. Three different outcome measures were examined: abstinence, amount of alcohol consumed at follow‐up, and improvement (life and drinking) at follow‐up. The generalizable conclusions were that females had significantly better outcome (78% abstinent) when treated according to a medical orientation. Male Behaviorally Impaired Drinkers had better outcomes when treated in Rehabilitation Professional Orientation (74% abstinent) and male alcoholics had the best outcome in Peer Group (60% abstinent), although male alcoholics achieved similar abstinence rates in Medical (59.5%) and Rehabilitation (55%) orientations.
Circadian and Genetic Effects on Ethanol Elimination in LS and SS Mice
Authors: Gilliam David M. , Collins Allan C.
Published: February 2008

Behavioral studies using mice have suggested circadian influences on response to ethanol. Studies examining possible circadian influences on ethanol elimination are ambiguous as to whether changes in elimination contribute to circadian variations in response. Therefore, the linear declines in blood alcohol concentrations (BACs) were assessed in long‐sleep (LS) and short‐sleep (SS) male mice at 0300, 0900, 1500, or 2100 hr following an intraperitoneal injection of either 2.5 or 4.1 g/kg ethanol. Overall mean BAC for LS mice was significantly higher than for SS mice at both ethanol doses. With the 4.1 g/kg dose, LS mean BAC was higher at 2100 hr than at 0900 hr. Both lines of mice exhibited faster elimination rates at 0300 and 0900 hr than at 1500 and 2100 hr. SS mice generally showed a more rapid decline in BAC than did LS mice at this dose. With the 2.5 g/kg dose, the rate of decline was faster at 0900 hr than at 2100 hr for both lines of mice. SS mice showed a significantly greater overall rate of decline than did LS mice. The line differences in blood alcohol concentration and elimination rate may have resulted from a change in the doses used to select these mice and may contribute to circadian influences on ethanol response.
Hospital Treatment of Alcoholism: A Profile of Middle Income Americans
Authors: Mendelson Jack H. , Miller Kenneth D. , Mello Nancy K. , Pratt Herbert , Schmitz Robert
Published: February 2008

3,411 first admissions for alcoholism treatment to nine proprietary hospitals were studied with standardized questionnaire and diagnostic instruments. Despite the patients' relative economic and social stability, severe patterns of addictive alcohol use had developed and persisted for many years with a high incidence of alcohol‐related and intercurrent medical disorders which required prompt medical intervention. Although most patients had a personal physician, less than 9% of referrals for hospital treatment for alcoholism were made by physicians; most patients responded to television outreach programs, recommendations by former patients or were self or family referred. This survey shows that persons who are neither socially disadvantaged nor economically deprived may have severe alcohol‐related problems. Such patients constitute a significant challenge to the medical profession to develop strategies for early intervention and more efficacious treatment.
Prolonged Feeding of Ethanol to the Young Growing Guinea Pig: 1, The Effect on Protein Synthesis in the Afterloaded Right Ventricle Measured in Vitro
Authors: Schreiber Sidney S. , Evans Carole D. , Reff Francine , Rothschild Marcus A. , Oratz Murray
Published: February 2008

Newly weaned guinea pigs weighing approximately 300 g were fed normal laboratory diets with drinking water containing 5.5% ethanol as the sole source of liquid for periods of 8–11 weeks. Growth was continuous with this diet. After this period, hearts were removed from anesthetized animals and perfused for 3 hr in a perfusion system in which pressure may be induced in the right ventricle In the face of constant coronary flow. Protein synthesis, assayed from the incorporation of labeled lysine and phenylalanine, was compared to that in hearts from identically treated weight‐matched control animals who had been drinking water without ethanol. Protein synthesis in hearts from ethanoWrinking animals was decreased in the right ventricles exposed to normal pulmonary pressure, but was unchanged in the contracting but not working left ventricles. The data suggest that prolonged exposure even to low levels of ethanol in the growing animal may interfere with the cardiac protein synthetic response to the normal work stress.
Tolerance to Ethanol Hypothermia in Inbred Mice: Genotypic Correlations with Behavioral Responses
Authors: Crabbe John C. , Janowsky Jeri S. , Young Emmett R. , Kosobud Ann , Stack Julianne , Rigter Henk
Published: February 2008

Hypothermia was studied 5 min before, and 30 and 60 min after intraperitoneal administration of ethanol (3 g/kg) in 20 inbred strains of mice. Ethanol was given daily for 8 days, and temperatures were taken on Days 1, 3, 5, and 8. Tolerance was indexed by the reduction in hypothermia over days. There were large strain differences in baseline temperature, the hypothermic effect of ethanol, and in development of tolerance to hypothermia. Some strains of mice (DBA/1J, DBA/2N, MA/MyJ, and PL/J) did not develop tolerance to the hypothermic effect of ethanol. Initial sensitivity to the hypothermic effect of ethanol was significantly genetically correlated with tolerance development, indicating control of these responses by common genes. Ethanol‐induced changes in activity and ataxia, as well as blood ethanol concentrations, were also assessed. Although there were significant strain differences in activity reduction, ataxia, blood‐ethanol concentrations, and changes in these parameters during the course of chronic treatment, none of these variables could explain the genetic differences in hypothermic sensitivity and tolerance.
Acute Effect of Ethanol on Metabolite Concentrations of Dog Pancreas in Vivo
Authors: Guynn Robert W. , Kuo Y.‐J. , Shanbour Linda L.
Published: February 2008

Sections of dog pancreas were freeze‐clamped before and 1 hr after oral administration of 1 g/kg of ethanol in anesthetized, respirated, 24‐hr‐fasted animals, and multiple metabolites were determined in the perchloric acid extract of the frozen tissue. In spite of the fact that the pancreas contained little or no alcohol dehydrogenase activity (<0.01 lU/g of tissue), significant metabolite changes did occur. Although arterial oxygenation was constant and adequate (pO2= 100±7 mM Hg) there was a significant 1.7‐fold rise in L‐lactate and fall in the cytoplasmic free [NAD+]/[NADH] ratio from 719±87 to 453±88 after ethanol. Except for a tendency for L‐malate and L‐α‐glycerolphosphate to parallel the rise in L‐lactate, there was little consistent disturbance in the remainder of the glycolytic metabolites (glucose, glucose 6‐phosphate, pyruvate, 2‐ketoglutarate, citrate, 3‐phosphoglycerate, etc.) or in high energy intermediates and related compounds (ATP, creatine phosphate, AOP, Pi, creatine). There was, however, an unexpected and significant fall in the levels of the major transaminating amino acids, L‐glu‐tamate, L‐aspartate, and L‐alanine. The results can be only partially explained by an influence of blood‐borne metabolites and imply significant effects of ethanol on the metabolism of the pancreas in vivo not directly mediated through alcohol dehydrogenase. Evidence is presented suggesting that both L‐alanine and L‐aspartate aminotransferases are functioning near equilibrium in the pancreas in vivo.
Inhibition of Placental Amino Acid Uptake in Rats Following Acute and Chronic Ethanol Exposure
Authors: Henderson George I. , Patwardhan Rashmi V. , McLeroy Sandra , Schenker Steven
Published: February 2008

The effects of acute and chronic maternal ethanol consumption on in vitro placental uptake of a‐amino‐isobutyric acid (AIB), cycloleucine, L‐alanine (Ala), L‐leucine (Leu), and L‐lysine (Lys) were determined. Ethanol (4 g/kg, po) administered 2 hr prior to sacrifice, reduced (p < 0.05) placental villous net uptake of cycloleucine and Ala by 29%. Prior chronic ethanol consumption depressed (p < 0.05) placental uptake of AIB (38%), cycloleucine (45%), Ala (35%), Leu (25%), and Lys (34%). In vitro exposure of previously untreated villous fragments for 2 hr to 2 mg/ml of ethanol reduced (p < 0.05) the net uptake of AIB and cycloleucine by 24% and 31%, respectively, whereas the minimum concentration of acetaldehyde required to cause a significant inhibition was 310 for AIB and 465 μM for cycloleucine. Ethanol (3 mg/ml) had no effect on AIB or cycloleucine net uptake if sodium was omitted from the incubation media. The efflux of AIB (10‐6 M) and cycloleucine (10–6 M) from villous tissue was unaffected (p> 0.05) by either ethanol (3 mg/ml) or acetaldehyde (600μM) and obeyed first order kinetics. It was concluded that acute, and especially chronic, maternal ethanol consumption can depress the placental uptake of a variety of amino acids in the rat and, in the acute setting, the effect was on a sodium‐dependent system involved in amino acid influx into placental ceils.
Piracetam Reduces Alcohol Withdrawal in Mice without Potentiating Alcohol Sedative Effects
Authors: Serby Michael , Segamick David J. , Cordasco Donna Mandio , Rotrosen John
Published: February 2008

Piracetam reduced the intensity of withdrawal behavior in mice that had been exposed to ethanol for 4 days. However, in contrast to other antiwithdrawal agents, piracetam did not potentiate the sedative effects of acute ethanol administration. While the mechanism of action of piracetam is unknown, these findings suggest that piracetam elicits its antiwithdrawal effects by a mechanism differing from that of other agents.
The Feeding of Alcohol in Liquid Diets: Two Decades of Applications and 1982 Update
Authors: Lieber Charles S. , DeCarli Leonore M.
Published: February 2008

The technique of feeding ethanol as part of a totally liquid diet was invented two decades ago and its successful application for the intervening period is reviewed. This technique results in much higher ethanol intake than with conventional procedures. As a consequence, various complications observed in alcoholics were reproduced in animal models, including fatty liver, hyperlipemia, various metabolic and endocrine disorders, tolerance to ethanol and other drugs, physical dependence and withdrawal, the fetal alcohol syndrome and, in the baboon, liver fibrosis and cirrhosis. Variations of the liquid diet formulation are compared and three standardized basic formulas are being proposed for the rat: (1) a regular diet, comparable to the diet previously referred to as the “Lieber‐DeCarli Formula” and suitable for most experimental applications, particularly those intended to mimic the clinical situation in which the various effects of alcohol occur in the setting of liver changes characterized by a fatty liver; (2) a low fat diet comparable in all respects to the preceding diet but with a lower fat content, intended to minimize the hepatic changes; and (3) a high protein formula particularly useful in those circumstances in which an oversupply of dietary protein might be recommended (i.e., pregnancy and lactation).
The Interaction of Chronic Alcohol Consumption and Aging on Brain Structure and Function
Authors: Freund Gerhard
Published: February 2008

Cognitive performance declines moderately with normal aging and severely with pathological aging. A similar range of intellectual impairment has been described in association with prolonged alcohol consumption. It is doubtful that all types and degrees of alcohol‐associated impairments of cognitive function are attributable only to thiamin deficiency. Evidence from human and animal data indicates increasingly that alcohol per se has direct CNS toxic effects as well, and it is dangerous to suggest that adequate thiamin consumption alone would prevent all CNS toxic effects of chronic alcohol consumption.

If a direct role of ethanol in CNS toxicity is accepted, it becomes important to study the molecular basis of the behavioral impairment caused by both aging and alcohol abuse in order to develop rational treatment and prevention. An entire spectrum of relationships is possible between aging and alcohol‐related CNS changes. At the one end of the spectrum could simply be deficits additive at the behavioral level but caused by different molecular events. Conversely, molecular processes of biological aging could interact with molecular effects of ethanol, potentiating each other and culminating in an accelerated aging process. Many pathological mechanisms could lead to an irreversible loss of neuronal cell bodies. However, changes in peripheral cell processes, including the synapses, may be equally important in limiting interneuronal communications that result in behavioral deficits. Some changes could even be limited to a decrease of numbers or affinity of synaptic receptor molecules of a particular region. From the human and animal data reviewed, chronic ethanol consumption appears to increase some behavioral deficits caused by aging. What the exact interrelationships are at the molecular basis for the behavioral changes is not yet clear.
Examination of Alcoholics by Computed Tomographic (CT) Scans: A Critical Review
Authors: Wilkinson D. Adrian
Published: February 2008

Neuroradiological studies have consistently demonstrated that alcoholics have morphological abnormalities of cortical, ventricular, and cerebellar structures suggesting brain atrophy. This atrophy is weakly correlated with impaired psychological test performance. Because brain atrophy and intellectual impairment can also be found in normal aging it is necessary to compare alcoholics with age‐matched control subjects.

It is currently unknown if alcohol‐associated brain atrophy and intellectual impairment are the result of conditions preceding alcohol consumption or conditions only indirectly related such as head trauma or other associated diseases. Direct alcohol toxicity would be supported by quantitative alcohol‐atrophy dose‐response relationships and by a partial reversal of atrophy and functional impairment following abstinence from alcohol.

Because of methodological difficulties inherent in neuroradiological research, data on the exact pathogenesis of abnormalities in alcoholics have not been produced. The design of such studies can be improved to increase the probability that the causes of brain atrophy will be elucidated.
Adult Rat Hepatocytes in Primary Culture. VI. Developmental Changes in Alcohol Dehydrogenase Activity and Ethanol Conversion during the Growth Cycle
Authors: Lad Pushkaraj J. , Shier W. Thomas , Skelly Harold , Hemptinne Bernard De , Leffert Hyam L.
Published: February 2008

Proliferation‐competent primary ‘monolayer’ cultures of adult rat hepatocytes that display a repertoire of differentiated functions have been characterized for growth state‐dependent expression of alcohol dehydrogenase activity (ADH; EC 1.1.1.1). Following hepa‐tocyte isolation and early during in vitro lag phase, ADH ‘per cell’ is equivalent to control adult liver tissue levels. Upon entry into and progression of logarithmic growth, ADH declines biphasically to about 2% of control levels (halftime rate, R[disappearance]= 3.4 and 7.4 hr; days 0‐is(halftime rate, R[disappearance]= 3.4and 7.4, respectively). increases biphasically as hepatocytes enter and remain in stationary phase (R[disappear]= 3.9 and 11.1 hr; days 6–10 and 10–14, respectively). Ultimately, control ADH is restored. Similar ‘U‐shaped’ curves occur when rates of conversion of [14C]ethanol into CHCI3:CH30H (2:1) extractable material are measured. By this criterion, 10‐ to 13‐day‐old hepatocyte cultures convert ethanol or [14C]acetate 10 times faster than stationary‐phase 3T3 fibroblasts' (3000 or 12,000 cpm/106 cells/24 hours versus 200 or 800 cpm/106 cells/24 hr, respectively). Both conversion processes in matured hepatocyte cultures depend on extracellular glucose levels unlike the nonhepatocyte system. Furthermore, depending on the growth state, [14C]ethanol conversion in hepatocyte cultures is inhibited up to 73% by 1 mil pyrazole, a specific ADH inhibitor. At higher initial ethanol levels (50 mil), pyrazole blockade is ineffective. The results indicate that, in this long‐term culture system, normal adult hepatocytes retain non‐ADH ethanol‐converting enzymes and pharmacologically‐sensitive ADH. Changes in the latter enzyme's activity levels in culture appear to simulate normal developmental changes in hepatic ADH in the intact animal.
Continuum versus Premature Aging Theories of Chronic Alcoholism
Authors: Cermak Laird S. , Peck Elizabeth
Published: February 2008

An attempt is made to differentiate, both theoretically and experimentally, the continuum theory from the premature aging theory of the chronic effects of alcohol on verbal information processing. It is argued that the continuum model necessitates a demonstration of differential ‘pattern’ of performance between alcoholics and normals in as much as alcoholic Korsakoff patients (at one end of the continuum) do demonstrate such patterns. Premature aging theories, on the other hand, need to demonstrate only subnormal performance by alcoholics relative to their contemporaries. Two experiments designed to assess these theories provided some evidence for premature aging but none for the continuum theory.
Effects of Ethanol and Temperature on Glucose Utilization in the In Vivo and Isolated Perfused Mouse Brain
Authors: Towell John F. , Erwin V. Gene
Published: February 2008

A [14C]2‐deoxy‐d‐glucose technique was used to investigate the effects of ethanol and temperature variation on the rate of glucose utilization in the isolated perfused mouse brain. Glucose utilization rates in six regions of the isolated perfused mouse brain at 37°C were similar to the rates in comparable regions of the in vivo mouse brain. The temperature dependence of the glucose utilization rate in the perfused mouse brain suggests that a change in the rate‐limiting step of cerebral glucose metabolism occurred between 28°C and 32°C. To investigate the possible involvement of temperature‐dependent membrane phase transitions, brain perfusions were performed with a medium containing ethanol which is known to increase membrane fluidity. Perfusion of the mouse brain with a fluid containing 87 mm ethanol (400 mg/dl) resulted in decreases in the glucose utilization rates at 37°C but not at 28°C. At 28°C, ethanol produced an increase in glucose utilization in the medulla‐pons and in the cerebellum of perfused brains. In vivo rates of cerebral glucose utilization in two lines of mice selectively bred for differences in ethanol‐induced sleep time indicated that no differences in basal metabolism or following a 4‐g/kg dose of ethanol existed between the two lines. Interpretations of ethanol's differential effects on cerebral glucose utilization rates in the isolated perfused mouse brain at 28°C and 37°C are presented along with a discussion of the apparent discrepancies observed when in vivo and perfused brains are treated with equivalent concentrations of ethanol.
Chromosomal Aberrations in Chronic Male Alcoholics
Authors: Badr Fouad M. , Hussain Farida H.
Published: February 2008

A group of 23 male heavy drinkers was studied cytogenetically, and the results were compared with those obtained from a control group of 50 non‐drinkers. The data are based on karyological analysis of dividing lymphocytes in 72‐hr blood cultures. Alcoholics revealed a significantly higher frequency of numerical and structural chromosomal aberrations. Chromosome rearrangements were observed only among alcoholics. The most frequent exchange type was dicentrics (0.02 per cell, constituting 65.1% of the total exchanges), followed by reciprocal translocations (0.005 per cell), and pericentric inversions (0.002 per cell). The significance of the presence of these types of chromosomal aberrations in the blood of alcoholics is discussed in terms of its prevalence and association with known syndromes and diseases. The possible effects and/or interactions of other factors such as duration of alcohol abuse, drugs, and smoking were also emphasized.
Alcohol Consumption and the Diet‐Heart Controversy
Authors: Barboriak Joseph J. , Gruchow Harvey W. , Anderson Alfred J.
Published: February 2008

The effectiveness of dietary changes as a means of reducing blood lipid levels and ultimately controlling the development of coronary heart disease has been debated for many years. The possible effects of alcohol consumption on blood lipids were usually not considered. Our findings indicate a significant positive correlation between the extent of coronary artery occlusion and total plasma cholesterol levels and a negative association between the coronary occlusion and high density lipoprotein (HDL) cholesterol. Since moderate alcohol consumption increases the HDL cholesterol levels, one can also postulate that it affects coronary artery lesions. The attenuating effect of alcohol on the coronary occlusion was negated by sporadic drinking of large amounts of alcohol. In evaluating the possible effect of alcohol on coronary artery disease, it is also necessary to consider its addictive potential as well as other untoward sequelae of alcohol consumption such as hypertension, damage to the myocardium, and increased prevalence of malignancies.
The Hypothalamic‐Pituitary‐Adrenal Axis in Alcoholics
Authors: Fuente Juan R. de La , Rosenbaum Alan H. , Morse Robert M. , Niven Robert G. , Abboud Charles F. , Jiang Nai‐S. , Schatzberg Alan F.
Published: February 2008

The hypothalamic‐pituitary‐adrenal axis of a group of patients suffering from alcoholism was studied by determining their plasma corticosteroid levels and urinary‐free cortisol excretion before and after administration of 2 mg of dexamethasone. The patients were recently abstinent from alcohol and were found to be in a hypersecretory state. However, the axis appeared to be intact because they were able to suppress when steroid was given exogenously.
Deficiencies of Clinical Trials of Alcohol Withdrawal
Authors: Moskowitz Gail , Chalmers Thomas C. , Sacks Henry S. , Fagerstrom Richard M. , Smith Harry
Published: February 2008

Eighty‐one therapeutic trials of alcohol withdrawal were found that have been published in English since 1954; controls were randomized in 29 (RCTs). Two thousand three hundred thirteen patients were randomized. Variable pretreatment description prevented estimates of delirium tremens and convulsion prevalence, but only four deaths were reported. Endpoints were thus entirely subjective in these moderately ill patients. Protocol quality of the RCTs was graded by a previously developed system for evaluating adequacy of descriptions, blinding, and essential measurements. Mean score obtained was.49 ±.03 (1 se). (A perfect paper would score 1.00.) Data presentations and statistical analyses scored.18 ±.03. There was little evidence of improvement of scores over time. Papers lacked confidence intervals, proper handling of dropouts, and ade quate details of side effects. In five RCTs, six comparisons showed that benzodiarepines are clearly superior to placebo (p >.001), but conclusions about comparisons with other drugs were not possible. In none of eight “negative” comparisons was the probability of a type II error (β) considered. Discovery of more effective syptomatic agents or methods of reducing the death rate will require more rigid protocols and analyses as well as larger studies to allow the use of more critical endpoints such as occurrence of delirium tremens, convulsions, or death.
Male Sexual Dysfunction as Related to Alcohol Consumption: A Pilot Study
Authors: Mandell Wallace , Miller Connie M.
Published: February 2008

Personal interviews were conducted with 44 male volunteers consecutively admitted to outpatient treatment in a county alcoholism program. Fifty‐three per cent of the subjects were still drinking minimally or in moderation at the time of the interview. Quantity, frequency, and duration of drinking, from onset of regular drinking to present, were related to sexual dysfunctions. During heavy drinking, 59% of patients experienced erection dysfunction, 48% repotted ejaculation incompetence, and 84.4% had experienced at least one kind of sexual dysfunction.
Human Blood Acetaldehyde Levels: With Improved Methods, a Clearer Picture Emerges
Authors: Lindros Kai O.
Published: February 2008

New reliable methods for the determination of acetaldehyde in human blood, either from separated plasma or from acidprecipitated whole blood, demonstrate that the blood of healthy Caucasians contains at most only extremely small amounts of acetaldehyde (>1 μM) after moderate alcohol intoxication. On the other hand, among about 50% of the Japanese population ethanol ingestion results in elevated blood acetaldehyde levels (10–50 μM) with consequent unpleasant cardiovascular responses such as facial flushing and tachycardia, apparently because of a lack of one of the acetaldehyde‐oxidizing aldehyde dehydrogenase isozymes.

Elevated acetaldehyde levels may eventually occur also among intoxicated Caucasian alcoholics, primarily as a consequence of abuse‐induced loss of hepatic aldehyde dehydrogenase activity, but accentuated by an accelerated ethanol oxidation rate. The elevation is probably reversible, since no acetaldehyde IS seen In alcoholics after abstinence and hospital treatment. There is thus little evidence that an elevation of acetaldehyde could serve as a marker for predisposition for alcoholism.
Cognitive and Electrophysiologic Parameters during Ascending and Descending Limbs of the Blood Alcohol Curve
Authors: Pishkin Vladimir , Lawrence Betsy E. , Bourne Lyle E.
Published: February 2008

This study examined the effects of acute alcohol ingestion and prior success or failure upon cognitive performance of 40 healthy, nonalcoholic subjects, during both the ascending and descending limbs of the blood alcohol curve. Measures of physiological arousal were made with frontal/laryngeal electromyographic and skin conductance response level parameters. Major findings were: (1) cognitive performance was impaired by alcohol ingestion; (2) autonomic arousal was significantly greater after alcohol than after placebo; (3) number and amplitude of skin response were greater on the ascending than on the descending limb; (4) the anticipated effects of failure on cognitive performance were ameliorated by alcohol; and (5) differential effects of alcohol on the psychophysiological parameters were demonstrated.
Studies on the Differences in NaK‐ATPase and Lipid Properties of Liver Plasma Membranes in Long Sleep and Short Sleep Mice
Authors: Zysset Thomas , Sutherland Eileen , Simon Francis R.
Published: February 2008

Activity of NaK‐ATPase, the biochemical equivalent of the sodium pump, may be reguiated by several factors including hormones, drugs, and inheritance. To evaluate further the possibility of genetic control, we investigated hepatic NaK‐ATPase in mice selectively bred for differences in ethanol‐induced sleep time, designated long sleep (LS) and short sleep (SS). In SS mice, specific acitivity of NaK‐ATPase was 65% higher than in LS. Other plasma membrane enzymes were also increased in SS including alkaline phosphatase (176%), leucine aminopeptidase (115%), 5′‐nucleotidase (49%). In contrast, basal adenylate cyclase and insulin binding, sodium do‐decyl sulfate polyacrylamide gel electrophoresis patterns, and the cytosolic enzyme tyrosine aminotransferase were similar. Altered membrane lipid composition did not account for these differences since the cholesterol:phospholipid ratio and the enzyme activity response after addition of benzyl alcohol to membrane preparation were similar in both strains.

Kinetic analysis of NaK‐ATPase activity showed a similar Km, but Vmax was 60% increased in SS mice. Using sodium‐dependent binding of [γ32P]ATP, a comparable increase in enzyme units was demonstrated. Since half‐maximal ouabain inhibition was similar, differences in NaK‐ATPase isoenzymes are unlikely. Differences in NaK‐ATPase between LS and SS appear to be specific to the liver since activities were not different in kidneys and muscles. Induction of NaK‐ATPase with tri‐iodothyronine (T3) showed greater responses in LS (+53%) than in SS (+13%). These changes may relate to a post‐receptor abnormality, since malic enzyme, a thyroid‐responsive enzyme, was higher basally in LS mice, but similar to NaK‐ATPase, the response to T3 administration was blunted in SS mice.

To evaluate a possible link between NaK‐ATPase activity and resistance to the hypnotic effect of ethanol, we examined inbred strains of mice with shorter (C57BL/6J) and longer (DBA/2J) ethanol sleep times. In contrast to LS/SS mice, NaK‐ATPaae was higher In DBA and lower in C57. Our study adds an animal model of genetically controlled differences in NaK‐ATPase, which is localized only to the liver. Although there seems to be no relationship between the different NaK‐ATPase activity in LS and SS mice and their different response to ethanol, this model is of potential interest for the study of mechanisms leading to ethanol‐induced liver disease.
Inhibition of Testosterone Production by Rat Leydig Cells with Ethanol and Acetaldehyde: Prevention of Ethanol Toxicity with 4‐Methylpyrazole
Authors: Santucci L. , Graham T. J. , MD David H. Van Thiel.
Published: February 2008

The toxic effects of ethanol and acetaldehyde on testosterone biosynthesis were examined in vitro using isolated Leydig cells prepared from adult rat testes. The ability of methylpyrazole, an inhibitor of alcohol dehydrogenase, to prevent the toxic effects of ethanol on testosterone production was investigated. Ethanol was found to inhibit gonadotropin‐stimulated testosterone production in a dose dependent fashion. Concentrations of ethanol (25 mg/100 ml), one‐fourth the legal limit of intoxication in man, were shown to reduce testosterone levels by 44% as compared to the controls. Acetaldehyde at micromolar concentrations also inhibited testosterone biosynthesis. The addition of 4‐methylpyrazole to the culture medium prevented the toxic effects of ethanol as determined by testosterone production. These studies suggest that ethanol per se may not directly inhibit testosterone biosynthesis. Rather, it would appear that acetaldehyde, the first product of ethanol metabolism, may be responsible for the toxic effects of ethanol upon Leydig cells at least in vitro.
Evidence for a Direct Inhibitory Effect of Ethanol upon Gonadotropin Secretion at the Pituitary Level
Authors: Schade Robert R. , Bonner Gregory , Gay Vernon C. , Thiel David H. Van
Published: February 2008

Mixed rat pituitary cells harvested from pituitaries obtained from adult male rats were maintained in tissue culture for periods up to 240 hr. Viability determined by trypan blue exclusion at the end of each experiment was greater than 90%. Basal secretory rats of luteiniring hormone (LH) into the culture medium were determined before and after the addition of ethanol (300 mg/100 ml) to the Incubation medium. Ethanol‐reduced (p <.01) LH Secretion of treated cultures were compared to control cultures. Based upon this preliminary in vitro study with rat tissue and on prior studies performed in man and animals, we suggest that ethanol inhibits LH secretion at the pituitary level.
Role of Acetaldehyde and Acetate in the Development of Ethanol‐Induced Cardiac Lipidosis, Studied in Isolated Perfused Rat Hearts
Authors: Kiviluoma Kai , Hassinen Ilmo
Published: February 2008

Isolated perfused rat hearts were used to study the effects of ethanol, acetaldehyde, and acetate on the cellular redox state and tatty acid metabolism in the myocardium. Ethanol had negligible effects on the cellular redox state but at high concentrations depressed the contractile activity and thereby secondarily the oxygen consumption. Acetaldehyde in concentrations below 50 μm had negligible effects on the redox state of the mitochondrial free NAD+/NADH couple, as studied by surface fluorometry of flavins and nicotinamide nucleotides. A reduction of NAD+ was observed with concentrations between 50 and 500 μm, while in the range of 0.5–1 mM the effect was biphasic, i.e., an initial reduction was followed by oxidation concomitantly with an increase in heart rate and peak systolic pressure. Acetate in rnillimolar concentrations caused an extensive reduction of mitochondrial NAD+ and an increase in the coronary flow. A mitochondrial acetaldehyde dehydrogenaae was revealed in the myocardium, having an apparent K, of 1.l μm for acetaldehyde. Acetaldehyde in 50μm concentration had no major effects on the uptake, oxidation, or lipid incorporation of oleate in the myocardium. Acetate in concentrations less than 2 mM did not affect the uptake of oleate into the myocardium, but did inhibit its oxidation and enhance its incorporation into tissue lipids in a dosedependent manner. 2 mM acetate caused a 91% increase in oleate incorporation into tissue lipids over 30 min.

The data can be interpreted as showing that acetaldehyde and acetate, the metabolites of ethanol, have metabolic effects on the myocardium, but only those of acetate are signlficant in concentrations encountered during ethanol oxidation in vivo. It is probable that acetate is involved in the development of ethanol‐induced myocardial lipidosis, inhibiting the oxidation of fatty acids, and channelling them into the esterification pathway.