bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Essential Fatty Acids in Alcohol Dependence and Tissue Damage
Authors: Glen Lain , Skinner Fiona , Glen Evelyne , MacDonell Lois
Published: April 2006

Evidence for the role of essential fatty acids in alcohol dependence is reviewed. If alcohol‐induced tissue damage is associated with impaired fatty acid and phospholipid metabolism, supplements of essential fatty acids might be beneficial in the treatment of alcoholics. The evidence for this effect is examined.
Fetal Alcohol Syndrome Associated with Trisomy 21
Authors: Bingol Nesrin , Fuchs Magdalena , Losub Silvia , Kumar Smita , Stone Richard K , Gromisch Donald S
Published: April 2006

Five cases of Down syndrome in association with fetal alcohol syndrome (FAS) are described. Four of the babies were full term, one was premature. Phenotypically these babies (3M:2F) had manifestations of both Down syndrome and FAS; growth deficiency was more pronounced than is expected in Down syndrome. All measurements, birth weight, length and head circumference were below ‐2 SD. All had congenital heart disease. Chromsome analysis confirmed 21 trisomy in every case.

Down syndrome and FAS may occur together, at random, in 1 in 525,0000 newborns in United States but 1 in 200,000 in our institution. Estimated incidence of FAS and Down syndrome in our institution was 1 in 6,600, a 30‐fold increase over the chance occurrence of these two conditions together. Mean age of mothers at delivery was 29.6 ± 9.3, statistically similar to the mean ages of mothers who delivered Down syndrome and FAS babies in our two hospitals, but was significantly higher than the mean age of mothers in our general population (p < 0.001).

All study cases had chronic alcoholic mothers as well as maternal grandmothers, suggesting that there is an increased incidence of trisomy 21 in children of second generation of alcoholic mothers.
Essential Fatty Acid Supplementation during Early Alcohol Abstinence
Authors: Wolkin Adam , Segarnick David , Sierkierski Joanna , Manku Mehar , Horrobin David , Rotrosen John
Published: April 2006

Interactions between ethanol, prostaglandins, and essential fatty acids (EFA) have led to the hypothesis that acute alcohol withdrawal and the sequelae of chronic alcoholism may be related to an EFA/prostaglandin deficiency. To test this hypothesis, EFA profiles in blood‐lipid fractions, serum liver enzymes, cognitive function, and alcohol craving were measured in 27 acutely abstinent alcoholics before and after a 3‐week double‐blind trial of EFA supplementation. Upon entry into the study, alcoholics had significant differences in EFA levels as compared to normal controls, and serum levels of liver enzymes tended to correlate with these EFA levels. After 21 days, cognitive function, alcohol craving, and liver enzymes all improved in both the EFA and placebo groups; most EFA levels also approached normal values. There were no treatment effects of EFA supplementation at the dose used.
Hypophosphatemia and Hypomagnesemia Result in Cardiovascular Dysfunction: Theoretical Basis for Alcohol‐Induced Cellular Injury
Authors: Brautbar Nachman , Altura Burton M
Published: April 2006

Although it has been known for many years that prolonged ingestion of ethanol may be associated with numerous side effects, among them cardiovasculr alterations, e.g., hypertension, cardiac arrhythmias, strokes, and cardiomyopathy, a direct cause and effect between alcohol and injury to the cardiovascular system has only been accepted recently. However, what mechanism is responsible for these cardiovascular alterations remains to be determined. Since it is well known that chronic alcohol consumption leads to hypophos‐phatemia and hypomagnesemia, we designed experiments to determine if controlled depletion of either phosphorous or magnesium (Mg2+) lead, in themselves, to cardiovascular disturbances and what effects these mineral depletions exert on myocardial cellular bioen‐ergetics. Biochemical studies were carried out on left ventricular muscle, including mitochondrial and myofibrillar preparations. With respect to phosphate depletion, myocardial creatine phosphate, ATP, and ADP levels were reduced. Phosphate depletion also reduced mitochondrial and myofibrillar creatine phosphokinase activities; significant alterations in mitochondrial oxygen consumption, acid‐extractable phospholipid precursors, and mitochondrial oxidation of long chain fatty acids were noted. With respect to magnesium depletion, significant reductions in inorganic oxygen consumption was also reduced. Utilizing these data, we have proposed several schemes for possible alcoholic‐induced myocardial and vascular injury.
Alcohol, Alcoholism, and Biological Rhythms
Authors: El‐Guebaly Nady
Published: April 2006

Chronobiological rhythms contribute to our understanding of the effect of alcohol and of several features of alcoholism. The observation of infradian periodicities suggests preventive seasonal strategies aimed at reducing the consumption of alcohol and its consequences. Circadian variations in blood alcohol levels and behavioral impairment indicate a complex temporal rhythmicity with both physiological and psychosocial determinants. Circadian differences are noted among possible mediators of susceptibility towards alcoholism. Ultradian patterns may be of prognostic value in assessing risks such as that of relapse during withdrawal from alcohol. Recommendations for future animal and human investigations are suggested.
Alcohol‐Dependent Men and Women in Detoxification: Some Comparisons
Authors: John Ulrich
Published: April 2006

Alcohol‐dependent women undergoing detoxification treatment in psychiatric wards are compared to men with respect to sociodemographic and treatment‐oriented variables. For these comparisons, patient documentation from all psychiatric hospitals in one large West German city were analyzed. Representativeness is shown by data of the general population of corresponding age. Findings are presented in relation to data of long‐term inpatient therapy. Results show that the detoxified women are socially less poorly integrated than men and suggest that our common ideas about a drinking career are based on experience with male alcoholics.
Gangliosides of Long Sleep and Short Sleep Mouse Cerebellum and Hippocampus and Cerebellar and Whole Brain Synaptosomal Plasma Membranes
Authors: Ullman M. David , Baker Rodney C. , Dietrich Richard A.
Published: April 2006

Gangliosides appear to be factors in CNS membrane responses to ethanol. Responses of membranes to ethanol might be influenced by the membrane concentration of gangliosides, the distribution of ganglioside molecular species, or the surface orientation of gangliosides at the plasma membrane surface. To determine the importance of these influences to the acute effect of ethanol, we have chosen to study them in long sleep (LS) and short sleep (SS) mice. This report presents our findings on (1) the composition of gangliosides from LS and SS mouse cerebellum and hippocampus, (2) the composition of gangliosides from synaptosomal plasma membranes (SPM) of LS and SS mice, and (3) the molecular species of cerebellar gangliosides from the two lines.

It has been found that GM1 is elevated in the cerebellum and in cerebellar SPM of LS mice compared to SS mice, but that there is no difference between the GMi concentration in the whole hippocampus of the two lines. Further, there are no differences in the molecular species of the cerebellar gangliosides of LS and SS mice.
Drinking Patterns and Drinking Problems in 1984: Results from a General Population Survey
Authors: Hilton Michael E.
Published: April 2006

Findings on alcohol consumption and alcohol problems from a 1984 general population survey are presented and compared to previous survey findings. Eighteen percent of all men and 5% of all women were classified as frequent heavy drinkers; 6% of all men drinkers and 2% of all women drinkers reported that they got “drunk” as often as once per week or more. A system for measuring drinking problems, based largely on the work of Cahalan and Room,1 is presented and explained. As when interpreting any system of measuring drinking problems in a general population survey, readers must be aware that the resulting prevalence rates are strongly influenced by arbitrary decisions about where cutpoints should be drawn. With this caveat in mind, the results show that 9% of men drinkers and 4% of women drinkers reported problematic drinking behavior at what is defined as a moderate level of severity. Similarly, 14% of men drinkers and 6% of women drinkers reported adverse tangible consequences of drinking at a moderate level of severity. The age and sex distributions of drinking, heavy drinking, intoxication, and drinking problems were as expected, with greater proportions of men than women reporting these things and greater proportions of younger than older drinkers reporting them.
Drug Use Among a Sample of Males Admitted to an Alcohol Detoxication Center
Authors: Ogborne Alan C. , Kapur Bhushan M.
Published: April 2006

Urine samples were obtained from 93% of a sample of 111 consecutive male admissions to a nonmedical detoxication center in Toronto. Analysis of these samples revealed that 51 (50%) had traces of drugs other than alcohol and that 12 (12%) were alcohol free. Benzodiazepines were the most frequently detected drugs and these were found in 32% of all samples. Barbiturates were detected in seven (7%) samples and cannabinoids in 10 (10%) samples. A wide range of urine alcohol concentrations was found and some samples had zero or low concentrations. Although alcohol urine concentrations were generally lower in samples containing other drugs, the distribution of urine alcohol concentrations was similar for samples containing only alcohol and those containing alcohol and some other drug. Of the 51 samples found to contain drugs other than alcohol, subjects' self‐reports were concordant in 27 cases (53%). Most of the discrepancies between self‐reports and urine analysis were due to the under‐reporting of the use of benzodiazepines. Subjects with drugs in their urine tended to be younger than others, but they were not distinguished with respect to their behaviors while in the detoxication center or length of stay. Those with the highest urine alcohol concentrations had shorter stays in the detoxication center. Implications for further studies are discussed.
Neuroglial and Neuroblastoma Cell Lines Are Capable of Metabolizing Ethanol Via an Alcohol‐Dehydrogenase‐Independent Pathway
Authors: Wickramasinghe S. N.
Published: April 2006

Two neuroglial cell lines (U‐251 MG and C6) had a substantial capacity to convert ethanol to acetate in vitro largely by an alcohol dehydrogenase (ADH)‐independent mechanism and three neuroblastoma cell lines (IMR‐32, NB41A3, and Neuro‐2a) had a lesser but significant ethanol‐metabolizing capacity which was also either partly or largely ADH‐independent. The ADH‐independent pathway of ethanol metabolism by neural cells appeared to be dependent on one or more isoenzymes of cytochrome P‐450. The data emphasize the possibility that the neurotoxicity of ethanol may be related to a relatively high ethanol‐metabolizing capability of neural tissue and particularly of neuroglial cells.
Two Generations of Maternal Alcohol Consumption in Mice: Effect on Pregnancy Outcome
Authors: Becker Howard C , Randall Carrie L
Published: April 2006

This study investigated whether female offspring of alcohol‐treated mothers are, themselves, more or less susceptible than control offspring to the deleterious effects of alcohol on the outcome of their own pregnancy. One group of pregnant C57BL mice was fed a liquid diet containing 25% ethanol‐derived calories (EDC) and another group was pair‐fed an isocaloric (0% EDC) control diet. A third group was fed lab chow ad libitum (LC). The female offspring resulting from those matings were subsequently mated upon reaching 90 days of age. These pregnant mice were then separated into three prenatal treatments (25% EDC, 0% EDC, and LC). On gestation‐day 19, second generation fetuses were removed by cesarean section, weighed, and sexed. Results indicated that number of implants, live births, and percent prenatal mortality did not differ between groups. However, fetal weight was lower in groups prenatally exposed to ethanol than in controls, regardless of the prenatal history of the mothers, themselves. More importantly, the data suggest that offspring of alcohol‐treated mothers who do not consume alcohol themselves during their own pregnancy may still have a tendency to have offspring of lower birth weight. On the other hand, if mothers prenatally exposed to alcohol do consume alcohol during their own pregnancy, the impact of fetal weight suppression is even greater than expected for in utero alcohol exposure alone. These effects may be due to the fact that mothers who were prenatally exposed to alcohol weighed less than controls at the time of becoming pregnant. As such, these data imply an increased risk for low birth weight offspring in children of alcoholic mothers who drink during their own pregnancy.
Effect of Acute Alcohol on Attention and the Processing of Hierarchical Patterns
Authors: Lamb Marvin R , Robertson Lynn C
Published: April 2006

Subjects received 100‐msec exposures of hierarchical patterns consisting of a large “global” letter composed of several smaller “local” letters. Subjects were to respond whether a target letter was present at the global or at the local level. In the Neutral Bias condition target letters occurred randomly and equally often at the global and local levels. In the Global Bias condition, 79% of the targets occurred at the global and 21% at the local level. In the Local Bias condition, 79% of the targets occurred at the local and 21% at the global level. Subjects indicated by pressing a key which of two target letters had appeared on that trial. Subjects received either a placebo drink, a drink containing 0.7 ml of Alcohol per kg body weight, or a drink containing 1 ml of Alcohol per kg body weight. Placebo subjects were better at detecting letters at the global than at the local level in the Global Bias condition, better at local than global in the Local Bias condition, and about equally good at both levels in the Neutral Bias condition. Alcohol had no effect on detection of letters at the local level in any of the bias conditions but reduced detection of letters at the global level except when subjects were biased globally. The data suggest that alcohol does not affect attentional capacity. Instead, alcohol seems to affect either how attentional capacity is allocated or the global processing mechanism itself.
Surfactant Deficiency with Decreased Opsonic Activity in a Guinea Pig Model of Alcoholism
Authors: Baughman Robert P , Roselle Gary A
Published: April 2006

Chronic alcoholism was induced in guinea pigs to quantitate the effect of alcohol on lung surfactant. Animals were studied after 6 weeks of treatment with either ethanol (ETH) or isocaloric dextrose‐saline (DEX) injections. The amount of surfactant retrieved by bron‐choalveolar lavage (BAL) was evaluated by measuring the quantity of phosphatidylcholine (PC) and disaturated phosphatidylcholine (DSPC) in the fluid. The amount of DSPC recovered from the ETH animals (40.9 ± 10.4 μg/ml of BAL fluid, mean ± SD) was significantly lower than from the DEX animals (82.7 ± 18.6 μg/ml of BAL fluid, p < 0.001). This decrease in surfactant was associated with impairment of the opsonic activity from BAL fluid in the ETH versus DEX animals using a standard assay of bacterial (Staphylococcus aureus) killing with normal polymorphonuclear leukocytes and BAL fluid as an opsonin. We conclude that in the guinea pig model of alcoholism, surfactant deficiency occurs and has physiologic importance in reduced bacterial killing.
Ascorbic Acid and Elevated SGOT Levels after an Acute Dose of Ethanol in the Guinea Pig
Authors: Susick Robert L. , Zannoni Vincent G
Published: April 2006

Male guinea pigs were maintained on a vitamin C‐deficient chow diet and supplemented with either 0.05 or 2.0 mg of ascorbic acid/ml drinking water for 3 weeks prior to receiving an intraperitoneal injection of 4.0 g of ethanol/kg body weight. The following biochemical parameters were measured prior to, and hourly for 12 hours after, ethanol administration: serum glutamic‐oxaloacetic transaminase (SGOT), serum glutamic‐pyruvate transaminase (SGPT), serum triglycerides, and blood ethanol clearance. The animals were killed 12 hours after ethanol administration and liver weight to body weight ratios and hepatic ascorbic acid concentrations determined. Acute ethanol administration resulted in a 12‐fold increase in SGOT levels in animals with hepatic ascorbic acid concentrations at or below 16 mg/100 g of liver. A marked reduction, 60%, in this increase was observed in animals that had concentrations of hepatic ascorbic acid above 16 mg/100 g of liver. No effect of hepatic ascorbic acid concentration was observed on elevated levels of SGPT, serum triglycerides, or blood ethanol clearance.
Developmental Changes in Alcohol Pharmacokinetics in Rats
Authors: Kelly Sandra J , Bonthius Daniel J , West James R
Published: April 2006

Developmental changes in the pharmacokinetics of alcohol could influence the outcome of alcohol exposure during different periods of postnatal development. Hence, the development of the ability to absorb and metabolize alcohol in the rat was examined by administering an acute dose (2.5 g/kg) of ethanol in milk formula by intragastric intubation to rats of 1, 2, 4, 6, 8, 10, 15, 21, 30, and 60 days of age. Each animal in a particular litter was assigned a different time point following intubation when its blood alcohol concentration (BAG) was determined from a tail blood sample. At all ages tested, maximum BACs occurred between 1.25 and 1.5 hr following intubation. However, maximum BACs decreased with age from 155 mg/dl in 1‐day‐old rats to 111 mg/dl in 60‐day‐old rats. Furthermore, the rate of alcohol clearance was slower in the younger rats. By linear regression analysis, the elimination rate of alcohol in 1‐day‐old rats was estimated to be 7.5 mg/dl/hr which increased to 42.2 mg/dl/hr in 60‐day‐old‐rats. By 8 hr following intubation, rats that were 21 days of age and older had completely cleared the alcohol, whereas the younger rats (1–15 days of age) had not. No consistent sex differences were seen in either the maximum BAC or clearance rate. Since developmental changes in the ability to clear alcohol occur throughout the first 60 postnatal days in the rat, controlling for these changes is essential when looking for critical periods of an organ's vulnerability to damage by alcohol.
Acupuncture Treatment of Alcoholic Recidivism: A Pilot Study
Authors: Bullock Milton L , Umen Andrew J , Culliton Patricia D , Olander Robert T
Published: April 2006

We performed a randomized trial of acupuncture on a group of 54 hardcore alcoholic recidivists to determine if sobriety could be achieved and episodes of drinking and/or Detox Center admissions be decreased by this mode of therapy. Patients in the treatment group received acupuncture points specific for the treatment of substance abuse; control patients received nonspecific points.

Significant differences in the two groups were noted at the end of the study. Patients in the treatment group expressed less need for alcohol (p < 0.003), and had fewer drinking episodes (p < 0.0076) and admissions to the Detox Center (p < 0.03) during the study than did control patients. THe majority of treated patients felt that acupuncture had a definite impact on their desire to drink, whereas only a few control patients noted this effect (p < 0.015).

The results of this study suggest that acupuncture may be able to interdict the cycle of alcoholic recidivism. Further investigation is needed to define the role of acupuncture in the treatment of alcoholism more precisely.

The authors wish to express their appreciation to Dr. Michael O. Smith for his encouragement and consultation during the course of this study, and to Drs. Alvin L. Schultz and Nicole Lurie for their critical review of the manuscript. Mary Kay Messner provided expert secretarial assistance.
Liver Toxicity Encountered in the Veterans Administration Trial of Disulfiram in Alcoholics
Authors: Iber Frank L , Lee Kelvin , Lacoursiere Roy , Fuller Richard
Published: April 2006

Alcoholic subjects (453) were randomly assigned to disulfiram or placebo therapy and followed for up to 12 months for drinking. Drinking status was determined from interviews of the subject and a household contact each 2 months and from the analysis of eight blood samples or 39 urines submitted at intervals during the year. Liver status was monitored each 2 months by obtaining serum alkaline phosphatase, bilirubin, and AST. Sensitive criteria were arbitrarily selected to identify about 1/5 of the patients with episodic elevations of liver tests. There was no relationship of liver test elevations to disulfiram treatment. However, the elevated AST related significantly to drinking status (p= 0.004) as did elevated bilirubin (p= 0.044), but not elevated alkaline phosphatase (p= 0.146). Two hundred one patients had liver test elevations at least one time and were continued on drug, four were dropped. One hundred seventy‐nine of these patients were drinking, 22 were abstinent, and four were indeterminant. It is concluded that patients on disulfiram with minor liver test abnormalities are usually drinking.
Evaluation of an Oral Solution to Accelerate Alcoholism Detoxification
Authors: Iber Frank L.
Published: April 2006

Twenty‐five newly admitted patients were randomly assigned to supplemental treatment with an oral fructose mineral drink or a placebo solution. Nine pints were given in a double‐blinded study during the first 3 days. Observations of tremor, chlordiazepoxide requirements, patients perceptions, and observer perceptions of common withdrawal symptoms and signs and the serum levels of Zn, Mg, and potassium were made initially and after the treatment. Although the patients improved over the 4 days of observations by many of the criteria, there were no differences between those receiving active solution and placebo.
Hydroxyl Radical Generation by Microsomes after Chronic Ethanol Consumption
Authors: Dicker Elisa , Cederbaum Arthur I.
Published: April 2006

The effect of iron and other compounds known to be toxic because of the production of oxygen radicals, e.g., paraquat and menadione on the generation of hydroxyl radicals (OH) by microsomes from chronic ethanol‐fed rats and their pair‐fed controls was determined. In the absence of any additions, or in the presence of ferric‐chloride, ‐ADP or ‐EDTA, microsomes from the ethanol‐fed rats showed a 2‐fold increase in the production of OH. Paraquat and menadione increased the generation of ˙OH by microsomes from the ethanol‐fed and the pair‐fed controls to an identical extent and thus these promoters of oxidative stress were not any more effective in interacting with microsomes after ethanol treatment. Under all conditions, ˙OH generation was sensitive to inhibition by catalase, implicating H2O2 as the precursor of ˙OH, whereas superoxide dismutase was without any significant effect. A working scheme to accommodate aspects of the interaction of iron, menadione and paraquat with microsomes with the subsequent production of ˙OH is described. The fact that ˙OH generation by microsomes in the presence of several sources of iron such as unchelated iron or ferric‐ADP is elevated after chronic ethanol consumption could contribute to the hepatotoxic effects of ethanol. Studies on iron metabolism by liver cells and the effect of ethanol on the disposition of this critical trace metal are needed to further evaluate the role of oxygen radicals in the actions of ethanol.
Discordance between the Cortisol Response to Insulin‐Hypoglycemia and 30‐Minute ACTH Stimulation Test in Chronic Alcoholic Men
Authors: Knudsen G. Moos , Christensen H , Berild D , Melgaard B , Kirkegaard C , Hasselbalch H
Published: April 2006

An insulin hypoglycemia test and a 30‐min ACTH stimulation test was performed in 10 chronic alcoholic men, who had been abstinent from alcohol for at least one month. Attenuated serum cortisol responses were found in six of the patients despite a normal ACTH test. Four patients showed normal responses to both the insulin hypoglycemia test and the short ACTH test. No correlation was demonstrated between the cortisol response and the severity of alcoholism, cerebral atrophy, and peripheral neuropathy. It is concluded that in chronic alcoholism the short ACTH test may fail in disclosing hypofunction of the integrated hypothalamic‐pituitaryad‐renocortical (HPA) axis as assessed with the insulin hypoglycemia test.
In Vitro Effects of Ethanol on Erythrocyte Membrane Fluidity of Alcoholic Patients: An Electron Spin Resonance Study
Authors: Wood W. Gibson , Lahiri Suhas , Gorka Christine , Armbrecht H. James , Strong R
Published: April 2006

Chronic ethanol consumption has been shown to affect physical properties of membranes from animals as measured by electron spin resonance (ESR). This study compared for the first time the physical properties of erythrocyte membranes of alcoholic patients and control subjects using ESR procedures. Membrane fluidity was determined in the presence and absence of ethanol using the 5‐doxyl stearic acid spin‐label. Temperature‐dependent phase transition also was determined, as were comparisons between ESR parameters, at the 1st and 5th week after alcohol withdrawal. Ethanolinduced fluidity was significantly greater in membranes of control subjects compared with alcoholic patients. Baseline fluidity did not differ and the temperature at which the phase transition occurred was not significantly different between the two groups. The resistance of membranes of alcoholic patients to fluidization by ethanol was unchanged after 5 weeks of withdrawal. Comparisons between ethanol‐induced fluidization at the 1st and 5th week after withdrawal were not significantly different. These studies demonstrate differences in ethanol‐induced fluidization between alcoholic patients and control subjects that are consistent with earlier ESR studies using an animal model.
Family History of Alcoholism Does Not Predict Neuropsychological Performance in Alcoholics
Authors: Reed Robert , Grant Igor , Adams Kenneth M
Published: April 2006

We examined the relationship of history of alcoholism in first‐degree relatives to neuropsychological performance of alcoholics abstinent from several weeks to several years. Eighty‐four men were assigned to four groups based on “strength” of family history of alcoholism. The groups were: (1) “strong history,” a parent plus another first‐degree relative positive; (2) “moderate,” parent only positive; (3) “weak,” nonparent first‐degree relative only positive; and (4) “negative,” no first‐degree relative positive. There were no significant between‐group differences in NP performance. In other analyses there were no NP differences between alcoholics classified positive or negative purely on basis of paternal alcoholism, and no differences between subjects who had multigenerational versus unigenerational versus negative familial histories of alcoholism. It is concluded that genetic loading for alcoholism does not significantly affect the NP status of abstinent alcoholic groups equated for education, drinking history, and medical risk.
Static Ataxia as a Psychobiological Marker for Alcoholism
Authors: Hill Shirley Y , Armstrong Jennifer , Steinhauer Stuart R , Baughman Timothy , Zubin Joseph
Published: April 2006

Sons and daughters of male alcoholics were compared with the sons and daughters of controls on two measures of static ataxia. Increased sway was seen in the children of the alcoholic fathers who had an average of 3.7 first‐ and second‐degree relatives meeting criteria for alcoholism. The possibility that static ataxia may be a psychobiological marker for the more genetically mediated variant of alcoholism is discussed.
Expression of Prostaglandin Protective Functions in Gastric Mucosa Cells Cultured in the Presence of Ethanol: Effects on the Synthesis, Retention, Secretion, and Structure of Mucus Glycoprotein
Authors: Slomiany Amalia , Takagi Atsushi , Kosmala Malgorzata , Tsukada Hideaki , Slomiany Bronislaw L
Published: April 2006

The magnitude of prostaglandin [16, 16‐dimethylprostaglandin E2 (DMPGE2)] protection against ethanol action has been evaluated by studying the intracellular events leading to synthesis, modification, intracellular retention, and secretion of mucus glycoprotein in the rat gastric mucosal cell culture. When metabolic activity of the cultured cells was expressed as the amount of radioactive tracer in purified mucus glycoprotein, it was found that ethanol at low concentration (0.1 M) caused an 8‐ to 9‐fold increase in proline and a 5‐ to 6‐fold increase in palmitic acid incorporation into mucus glycoprotein; however, at 1.5 M ethanol, the synthetic processes ceased to function. In the presence of DMPGE2 (10 ng/ml), a 2‐fold increase in proline and a 3‐fold increase in palmitic acid incorporation into mucus glycoprotein were observed. A simultaneous addition of DMPGE2 (10 ng/ml) and ethanol (0.1–1.5 M), or pretreatment with DMPGE2 (10 ng/ml) for 20 min followed by the addition of ethanol (0.1–1.5 M), resulted in the stabilization of glycoprotein synthesis and secretion, and in restoration of the function at the level observed with DMPGE2 alone. The addition of 10 ng/ml of DMPGE2 caused a 32% increase in mucus glycoprotein secretion and an 11% increase in the intracellular content of the glycoprotein. The amount of mucus apoprotein precursor rose by 18%, and the fatty acylation of the synthesized peptides was up by 38%. Addition of DMPGE2, together with ethanol, prevented depletion of the intracellular glycoprotein stores. As observed with ethanol alone, the secretion was elevated by 16–27%, whereas the intracellular glycoprotein stores remained similar to those of controls. The synthesis of the mucus apoprotein precursor was highly sensitive to ethanol, and addition of DMPGE2 only partially prevented its inhibitory action. Pretreatment with DMPGE2, however, eliminated ethanol toxicity, and the precursor pool level remained elevated (28–30%) at all concentrations of ethanol tested. The fatty acylation, although positively affected by DMPGE2, decreased steadily with increments of ethanol concentration. The results show that DMPGE2 stabilizes the cellular membrane processes and thus imposes control over mucus glycoprotein synthesis, secretion, and its intracellular retention.
History of Chronic Alcohol Abuse Is Associated with Increased Nighttime Hypoxemia in Older Men
Authors: Vitiello Michael V , Prinz Patricia N , Personius Janelle P , Nuccio Maureen A , Ries Richard K , Koerker Richard M
Published: April 2006

The all‐night blood oxygen saturations (SaO2) of 19 older abstaining male alcoholics and 19 healthy age‐matched controls were recorded. The alcohol group had significantly lower nighttime mean and minimum oxygen saturations, significantly greater absolute (mean‐minimum) SaO2 desaturations, and significantly more desaturations below 90% compared with the control group. Additionally, the alcohol group had significantly more individuals with nighttime SaO2 means below 95% and nighttime SaO2 minimums below 90%. Finally, within the alcohol group, alcohol history was found to significantly correlate with nighttime mean and minimum SaO2 and absolute SaO2 desaturation. This preliminary study finds evidence that chronic alcohol abuse may predispose an individual to nighttime hypoxemia, and, inferentially, to sleep apnea. However, the effect is modest and it will need to be confirmed in larger, more carefully controlled studies.
Cognitive Dysfunction and Aging among Male Alcoholics and Social Drinkers
Authors: Page Ronald D , Cleveland Mary F
Published: April 2006

The relationship between aging and various drinking styles was examined. Four age groups (25–34, 35–44, 45–54, and 55–65 years) and four drinking styles (nondrinkers, social drinkers, alcoholics, and abstinent alcoholics) were compared. A battery of eight neuropsychological tests was administered to 322 men; 72 nondrinkers, 100 social drinkers, 58 abstinent alcoholics, and 92 alcoholics. Cognitive dysfunction related to aging was found to be a more significant factor than decline with alcohol use. Cognitive dysfunction associated with alcohol use was significant for three Wechsler Adult Intelligence Scale subtests; Vocabulary, Digit Symbol and Block Design. Alcohol‐related differences in intellectual functioning tended to diminish with increasing subject age.
Pyridoxine Deficiency and Ethanol‐induced Liver Injury
Authors: Diehl A. M. , Chacon M. A. , Potter J. J. , Rolfes D , Cruess D. F. , Mezey E
Published: April 2006

It has been suggested that pyridoxine deficiency may potentiate ethanol‐induced liver injury. Our purpose was to clarify the effect of pyridoxine deficiency on ethanol‐associated liver injury by comparing liver histology, serum liver enzymes, and the viability of cultured hepatocytes from pyridoxine‐deficient and pyridoxine‐sufficient rats that had been chronically fed ethanol‐enriched diets. Our data fail to substantiate that pyridoxine‐deficient animals are more susceptible to the hepatotoxic effects of ethanol than pair‐fed pyridoxine‐sufficient controls. Furthermore, the addition of pyridoxine to hepatocyte cultures fails to prevent in vitro cytotoxicity of added ethanol. Pyridoxine deficiency may augment ethanol‐induced enhancement of hepatic urea synthesis. These data suggest that pyridoxine deficiency may contribute to the abnormal plasma amino acid profiles and nitrogen balance of chronic alcoholics, but that it does not potentiate ethanol‐induced liver injury.
Interaction of Dichloromethane and Ethanol in Rats: Toxicokinetics and Nerve Conduction Velocity
Authors: Glatzel W. , Tietze K. , Gutewort R. , Pankow D.
Published: April 2006

The influence of a single combined administration of ethanol (174 mmol/kg per os) plus dichloromethane (1.6, 6.2, or 15.6 mmol/kg p.o.) on blood concentrations of the tested substances and of carboxyhemoglobin, and on nerve conduction velocity was studied in rats. The blood alcohol concentration was not influenced significantly by dichloromethane. The single high dose of ethanol completely inhibited the carboxyhemoglobin concentration increase due to dichloromethane, but did not prevent the dichloromethane‐induced decrease of nerve conduction velocity. It produced initially lower, then higher concentrations of dichloromethane in blood than values seen after administration of dichloromethane per se. Rats treated with ethanol plus dichloromethane showed a more pronounced decrease of nerve conduction velocity compared with rats administered dichloromethane only.
Calcium Differentially Alters Behavioral and Electrophysiological Responses to Ethanol in Selectively Bred Mouse Lines
Authors: Palmer Michael R. , Morrow Elizabeth L. , Erwin V. Gene
Published: April 2006

Sensitivity to the hypnotic action of ethanol has been found to increase in SS/lbg (SS) but not in LS/lbg (LS) mice after intracere‐broventricular (icv) administration of calcium. In the present investigation, a correlation was found between calcium‐induced changes in behavioral sensitivity and in the sensitivity of cerebellar Purkinje neurons to the depressant effects of locally applied ethanol. Cerebellar Purkinje neuron sensitivity was measured as the dose of ethanol pressure ejected from a multibarreled micropipette required to produce a 50% depression of spontaneous firing rate of single neurons. Administration of 0.2–0.4 μmol calcium chloride into the lateral ventricle of the brain increased the sensitivity of SS but not LS mice to the hypnotic behavioral effect of systemically administered ethanol. Similarly, Purkinje neuron sensitivity to locally applied ethanol was also enhanced in SS but not in LS mice 15 min following administration of calcium (0.25 μmol) icv. Furthermore, locally applied ethanol was more effective in depressing spontaneous Purkinje neuron discharge in SS mice when a 1 mM calcium solution was concomitantly pressure ejected with ethanol from the micropipette. Magnesium chloride did not mimic the effects of calcium on either behavioral or electrophysiological effects of ethanol, suggesting that the action of calcium is not a nonspecific effect of divalent cations. These data suggest that calcium‐dependent processes may be involved in behavioral and electrophysiological effects associated with ethanol intoxication. Further research will be required to determine if the genetically selected difference in ethanol sensitivity expressed in LS and SS mice is regulated by calcium mechanisms.
Prevalence of Low Monoamine Oxidase Function in Alcoholism
Authors: Faraj Bahjat A. , Lenton John D. , Kutner Michael , Camp Vernon M. , Stammers Thomas W. , Lee S. Reaves , Lolies Pat A. , Chandora Deen
Published: April 2006

Several studies have found a trend for low platelet monoamine oxidase activity (MAO) in alcoholism but with a great deal of overlap in MAO activity of alcoholics versus controls. The main objective of this study was to carry out a detailed assessment of MAO function that included the measurement of key kinetic parameters (i.e., Km, Vmax) in three groups of male subjects: (a) 51 hospitalized chronic alcoholics, (b) 16 recovering alcoholics with 2–10 years of abstinence, and (c) 21 controls. MAO activity was assayed radio‐chemically with [14C]tyramine as substrate (43–729 μM). The present study demonstrated that alcoholics had low platelet MAO activity (p < 0.05). Kinetic analysis revealed a substantial reduction (p < 0.01) in enzyme Vmax values of chronic and recovering alcoholics. Greater than 95% of the alcoholics had Vmax values lower than the smallest value of control subjects. Moreover, 100% of the alcoholics in both groups exhibited exceedingly low Vmax values that were below the 25th percentile of controls. In summary, results of MAO Vmax determinations provided us with a better separation of the alcoholics from controls. Measurements of platelet MAO function that include enzyme Vmax may provide us a reliable biochemical marker for alcoholism.
Carbohydrate‐Deficient Transferrin in Serum in Patients with Liver Diseases
Authors: Stibler Helena , Hultcrantz Rolf
Published: April 2006

Carbohydrate‐deficient transferrin (CDT) in serum was analyzed by isocratic microanion exchange chromatography at pH 5.65 followed by a transferrin radioimmunoassay in 102 patients with biopsy‐verified liver diseases. CDT values were normal in all of the 87 nonalcohol‐abusing patients irrespective of type or degree of liver disease. Thirteen of the 15 alcoholic patients (87%) with current abuse showed elevated CDT values while in abstaining alcoholics with remaining liver disease the values were normal. No correlations were found between CDT level and volume density of liver fibrosis or steatosis or values of a number of clinicochemical liver tests. The only significant correlation demonstrated was between CDT concentration and the level of present daily alcohol consumption in the alcoholic patients. These results indicate that CDT can be used as a marker of present but not previous alcohol abuse, even in patients with various liver diseases.
Chemical Monitoring of Disulfiram Compliance: A Study of Alcoholic Outpatients
Authors: Kofoed Lial L.
Published: April 2006

Poor compliance with disulfiram (Antabuse) therapy may reduce its efficacy in the treatment of alcoholism. This study was designed to examine two questions: (a) Could use of a chemical test for disulfiram ingestion be used clinically to improve disulfiram compliance and if so, (b) could improved disulfiram compliance contribute to improved compliance with other aspects of treatment? The results suggest that disulfiram compliance rates can be increased by clinical use of chemical monitoring data; however in this sample increased compliance with disulfiram did not correlate with improvements in other aspects of treatment compliance.
Genetic Correlation of Ethanol‐induced Ataxia and Cerebellar Purkinje Neuron Depression among Inbred Strains and Selected Lines of Rats
Authors: Palmer Michael R. , Wang Yun , Fossom Linda H. , Spuhler Karen P.
Published: April 2006

In the present study, we compared phenotypic differences in behavioral and neurophysiological responses to acute ethanol administration among six inbred rat strains. Genetic variation was found both for ataxia, as measured by loss of righting response (sleep time) after a hypnotic dose of ethanol, and for the depressant action of ethanol on the spontaneous discharge of cerebellar Purkinje neurons. Results from an analysis of covariance of these phenotypes, measured among the inbred strains, provided strong evidence for a high genetic correlation between sleep time and inhibition of cerebellar Purkinje neuron discharge in response to acute ethanol administration. However, ethanol metabolism was also found to correlate with the behavioral sensitivity of rats to ethanol. Preliminary data from the third generation of replicate lines of rats currently being selectively bred for high and low acute sensitivity to ethanol shows a trend toward divergence of both ethanol sleep time and neuronal sensitivity to acute ethanol. The conclusion from these data supports the hypothesis that the cerebellum is an important locus of ethanol action, and suggests that neuronal sensitivity to ethanol will continue to diverge between these rat lines as selection for the sleep time phenotype progresses.
Effect of Ethanol on Motor Performance and Hippocampal Population Spikes in Some Standard and Selectively Outbred Rat Strains
Authors: Sellin L. C. , Laakso P. S.
Published: April 2006

Ethanol sensitivity of Wistar and Long‐Evans rats was compared in vivo and in vitro. Ethanol was more effective in reducing motor performance in Long‐Evans than in Wistar rats, as determined by the tilting plane test. In addition, ethanol produced a greater reduction in the population spikes recorded from hippocampal slices (in vitro) of Long‐Evans rats compared to Wistar rats. When rats from the Wistar, Long‐Evans, and Sprague‐Dawley strains were crossbred and then selectively outbred for high (ANT) and low (AT) sensitivity to ethanol‐induced impairment of motor performance, no differences were observed in the ethanol sensitivity of the hippocampal population spike between these two strains. These data suggest that differences in ethanol sensitivity may exist among standard laboratory rodent strains. Selective outbreeding may reduce or eliminate the differences in ethanol sensitivity of brain regions or neurons other than those directly involved in producing the selected behavior. Therefore, it may be incorrect to assume a general difference in ethanol sensitivity when these traits are not coselected during out‐breeding, thus indicating different neuronal pools in terms of sensitivity to ethanol.
Psychophysiological Effects of Oral Ethanol in Alcoholics and Social Drinkers
Authors: Turkkan Jaylan S. , Stitzer Maxine L. , McCaul Mary E.
Published: April 2006

The acute and extended effects of ethanol ingestion were examined in five alcoholic subjects, and five “social” drinkers. Six physiological and four subjective report measures were taken before, during and up to 90 min after the ingestion of ethanol in three doses and placebo. Findings showed that alcohol exerted significant dose‐related physiological effects in the initial minutes of ingestion, and in extended analyses of physiological and subjective measures in both groups of drinkers. Alcoholics and social drinkers generally did not differ in their physiological responses to alcohol doses and placebo, while some evidence for tolerance to reported euphoric effects of alcohol in the alcoholic subjects was found. The possibility is raised that early physiological responses observed during ethanol ingestion may arise not only from pharmacological effects of the drink, but may also be evidence for conditional predrink responses.
Prediction of Posttreatment Drinking Outcome in a 2‐Year Out‐Patient Alcoholic Treatment Program. A Follow‐up Study
Authors: Öjehagen Agneta , Skjaerris Anne , Berglund Mats
Published: April 2006

Fifty alcoholics who attended a 2‐year out‐patient treatment program with standardized evaluations every third month were followed‐up 2 years after completion of the program. One patient refused to be followed‐up and four were dead. Corroboration was available in 78% of the cams. The number of abuse days from the second half‐year of therapy and forward was strongly related to the number of abuse days during the follow‐up period as were ratings both of drinking goal fulfillment and fulfillment of other treatment goals at termination of the treatment period. On the contrary initial characteristics and background data as well as the number of abuse days during the first half‐year were not related to number of abuse days during the follow‐up period. Our findings indicate that improvement during long term out‐patient treatment for alcoholism is stable during the following 2 yean with a socially stable sample.
Acute Cardiovascular and Metabolic Effects of Acetate in Men
Authors: Suokas Antti , Kupari Markku , Heikkilä Juhani , Lindros Kai , Ylikahri Reino
Published: April 2006

We studied the potential contribution of acetate to the cardiovascular effects of ethanol in 12 healthy male volunteers. Sodium acetate, or sodium chloride in control experiments, was infused i. v. at the rate of 0.033 mEq/kg/min for 60 min. Left ventricular function was examined by M‐mode echocardiography and systolic time intervals during infusion and for 60 min thereafter. Blood acetate rose during infusion from 0.19 ± 0.02 (mean ± SEM) to a maximum of 0.99 ± 0.08 mmol/liter. Changes in serum free fatty acids, glycerol, and ketone bodies indicate that acetate inhibited peripheral lipolysis. The volume of urine excreted during the acetate experiment (305 ± 37 ml) was significantly larger (p < 0.01) than during the chloride experiment (181 ± 21 ml). Left ventricular function did not differ between the experiments during the infusions even though at 45 min heart rate was increased by acetate (7%; p < 0.01, between infusions). After the infusion period, at 75 min the treatment by acetate increased cardiac output from the baseline by 17% (p < 0.05, between infusions), and decreased peripheral arterial resistance (19%, p < 0.05), and diastolic blood pressure (10%, p < 0.01). Circumferential fiber shortening velocity was increased during the acetate experiment maximally by 7% (p < 0.01) from the baseline at 120 min. These data indicate that acetate is an arterial vasodilator and a mild diuretic and may slightly improve myocardial performance in the concentrations encountered during ethanol metabolism in men.