bluuebunny/crossref_metadata_2025 huggingface dataset:
Diminished Proliferative Response of Con A‐blast Cells to Interleukin 2 in Adult Rats Exposed to Ethanol in Utero
Authors: Norman D. C. , Chang M‐P. , Castle S. C. , Van Zuylen J. E. , Taylor A. N.
Published: April 2006

The fetal alcohol syndrome is associated with altered immunity. We attempted to delineate the mechanism of the decline in cell‐mediated immunity observed by others by using rats which were exposed to alcohol in utero and tested for immune integrity 3 months after birth. We found that concanavalin A‐stimulated T‐lymphoblast (Con A T‐blast) cells that were obtained from ethanol‐exposed rats had significantly diminished proliferative responses to both crude and recombinant intedeukin 2 compared to those obtained from normal and nutritional controls. The blunted response of Con A T‐blast cells to intedeukin 2 may be a biomarker of fetal exposure to alcohol.
Neurotensin and Ethanol Interactions on Hypothermia and Locomotor Activity in LS and SS Mice
Authors: Erwin V. Gene , Su Nanwei C.
Published: April 2006

Ethanol, i.p., produced a greater dose‐dependent hypothermia in long sleep (LS) than in short sleep (SS) mice with significant decreases in rectal temperature observed only at doses greater than 3 g/kg, i.p. Likewise, at doses of 1 to 2 g/kg ethanol, i.p., these lines of mice differ markedly in locomotor activity. Neurotensin (NT), intracerebroventricular (I.C.V.), induced a similar hypothermia in both SS and LS mice at doses greater than 0.02 μg. Doses of ethanol (1.0 g/kg) or NT (0.005 μg, i.c.v.) that failed to cause hypothennia when administered separately produced a pronounced hypothermia when administered together. Potentiation of NT and ethanol‐induced hypothermia was greater in SS than in LS mice. Sensitivity to NT‐induced hypothermia was greater following i.c.v. administration than by infusion into the nucleus accumbens (NA) or the ventral tegmental area (VTA). Neurotensin, i.c.v. or intra‐NA, markedly inhibited ethanol‐induced increase in locomotor activity in both SS and LS mice; however, NT, intra‐VTA, did not alter the effects of ethanol on locomotor activity. The results suggest that NT and ethanol act in a synergistic manner on specific neuronal processes mediating thermoregulation and spontaneous motor activity.
Graded Neuropsychological Impairment and Elevated γ‐Glutamyl Transferase in Chronic Alcoholic Men
Authors: Irwin Michael , Smith Tom L. , Butters Nelson , Brown Sandra , Baird Steve , Grant Igor , Schuckit Marc A.
Published: April 2006

This study hypothesizes that distinct biochemical and metabolic disturbances associated with liver injury may be related to specific cognitive changes in alcoholics. In 132 alcoholic men admitted to an alcohol treatment program, increases in γ‐glutamyl transferase (GGT) values were correlated with impairment in several measures of visuoperceptual and visuoconceptual functioning. The association between plasma levels of GGT and neuropsychological performance was independent of the relative contribution of other laboratory measures of liver injury and of alcohol consumption histories. These observations support the hypothesis that elevated levels of GGT are distinctly associated with neuropsychological deficits and suggest that possible mechanisms beyond severe hepatic dysfunction and alcohol consumption underlie cognitive deficits in alcoholics.
Genetic Animal Models in the Study of Alcoholism
Authors: Crabbe John C.
Published: April 2006

Several methods have been applied to the study of the genetic determinants of ethanol (EtOH) sensitivity in animals. The use of inbred strains has indicated that virtually all responses to EtOH have a significant degree of genetic determination. Studies with large batteries of inbred strains have elucidated the common genetic control of several clusters of EtOH‐related variables. Studies with Recombinant inbred strains have identified single genes that may influence EtOH withdrawal severity and EtOH preference drinking. The best developed method has been the use of selective breeding to develop lines of mice or rats differing in EtOH‐related behavioral characters. Illustrative examples of potentially important research findings from experiments with LS/SS, P/NP, and WSP/WSR selected lines are discussed. Significant progress has been made in the use of genetic animal models to further our understanding of EtOH‐related traits. Several avenues for further research appear to be promising, and specific directions to be pursued are suggested.
Altered Ultrastructure of Lactating Rat Mammary Epithelial Cells Induced by Chronic Ethanol Ingestion
Authors: Vilaró Senén , Viñas Octavi , Remesar Xavier
Published: April 2006

The ethanol and acetaldehyde uptake by the lactating rat mammary gland as well as their effects on this gland at the ultrastructural level have been studied. The extraction of acetaldehyde was greater than that of ethanol both after chronic and acute ethanol treatment. Chronic ethanol administration resulted in a loss of the mammary cell polarization, in a reduction of the Golgi dictyosomal elements and in several abnormalities at the level of casein maturation and secretion, whereas lipid synthesis and secretion did not seem to be affected. Normal spherical casein micelles took on a filament‐like structure and casein vesicles appeared fused together forming ma‐crovesicles. All these alterations were specific of ethanol and/or acetaldehyde action and were not due to the associated malnutrition, as deduced from the lack of visible effects in the nutritional control group.
Effects of Mineral and Vitamin Supplementation on the Alcohol‐induced Fatty Liver and Microsomal Induction
Authors: Lieber Charles S. , DeCarli Leonore M.
Published: April 2006

In rats fed ethanol (36% of total energy) for 1 month as part of a standard liquid diet, significant increases in hepatic lipids, microsomal cytochrome P‐450, and in the activity of the microsomal ethanol oxidizing system were observed. Similar effects were noted in another group of animals treated with the same ethanol‐containing diet, except that the content of minerals and vitamins was increased by 50%. Body weight gains were also comparable in these groups. It is concluded that these effects of ethanol are not due to vitamin and mineral deficiency secondary to decreased food intake but rather can be attributed to ethanol itself.
Methionine Lowers Circulating Levels of Acetaldehyde after Ethanol Ingestion
Authors: Tabakoff B. , Eriksson C. J. P. , von Wartburg J‐P.
Published: April 2006

Methionine, administered to ethanol treated mice and rats, significantly reduced circulating acetaldehyde levels without altering circulating levels of ethanol. Hepatic levels of acetaldehyde were also lowered by methionine. Methionine was effective when given prior to or after the administration of ethanol, but the time course of the action of methionine suggested the necessity for metabolic transformation of this amino acid in order for the acetaldehyde‐lowering effect to be evidenced. Studies with humans, given methionine doses of approximately one‐tenth of those used with mice, indicated that methionine can also lower acetaldehyde in humans ingesting ethanol. Given the toxic characteristics of acetaldehyde, methionine may prove effective in reducing the damaging effects of ethanol ingestion.
Evaluation of Fibrosis in the Disse Space in Noncirrhotic Alcoholic Liver Disease
Authors: Robert Philippe , Champigneulle Bruno , Kreher Isabelle , Gueant Jean‐Louis , Foliguet Bernard , Dollet Jean‐Marc , Bigard Marc‐André , Gaucher Pierre
Published: April 2006

In 40 alcoholic noncirrhotic patients, we performed a fiver biopsy and determined the wedged hepatic vein pressure, the free hepatic vein pressure, and the intrahepatic vein pressure. In 27 of them, the serum concentration of the N‐terminal peptide of type 111 procollagen (PIIIP) and of the laminin P1 fragment was measured. All the liver biopsies were studied by light and transmission electronic microscopy. A score of collagenization of the Disse space (six classes) was performed using transmission electronic microscopy. 37 of the 40 patients had pathological collagenization of the Disse space which was correlated with intrahepatic pressure (p < 0.01). The laminin P1 blood level in patients (1.38 ± 0.51 U/ml) was increased, compared to the values of our controls (0.99 ± 0.10 U/ml, p < 0.01) and was correlated with the wedge hepatic vein pressure (p < 0.01). The PlllP blood level was not significantly increased except when Mallory bodies were found in hepatocytes (p < 0.05). The laminin P1 blood level seemed to be a good biological marker for detection of liver fibrosis in long‐term alcoholic intake.
Influence of Ethanol on Stiffness, Toughness, and Ductility of Femurs of Rats
Authors: Kusy Robert P. , Hirsch Philip F. , Peng Tai‐Chan
Published: April 2006

Recently, we reported that the ingestion of alcohol in rats reduced the mechanical strength of femurs. Our results showed that, as the dose exceeded 0.012 g of ethanol per gram of body weight, a significant (p<0.001) loss of “strength” occurred that was independent of sex according to the relationship

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In the present effort, the same flexure tests were reevaluated to include the parameters of stiffness, toughness, and ductility. These latest results confirm that the femurs of rats fed an ethanol liquid diet for 4 weeks are not only weaker but also more compliant and less energy absorbing. Although the femurs of rats fed ethanol are more ductile, the bones are more prone to fracture in fatigue and impact circumstances as well as under simple loading situations. The rat may be an appropriate model to study the mechanisms that lead to the higher incidence of fractures in the alcoholic human.
Effect on Liver Cirrhosis and Traffic Accident Mortality of Changing the Number and Type of Alcohol Outlets in Western Australia
Authors: Ian Smith D.
Published: April 2006

A longitudinal study with a 6‐year before‐period and a 9‐year after‐period was conducted to determine the effect of changing the number and type of alcohol outlets in Western Australia relative to a control State. During the 1974 to 1982 after‐period Western Australia had a 16.0% increase in the hotel, tavern, and store rate in comparison to the control State, but a 17.4% decrease in the rate of licences for licensed clubs, restaurants, and all other licences. Consistent with previous correlational research, the above changes were associated with significant increases in Western Australia for male (+24.3%) and female (+29.3%) liver cirrhosis mortality, but a significant decrease in male driver and motorcyclist mortality (‐22.1%). Attention is drawn to the value of longitudinal studies to examine both the negative and positive effects of changing the number and type of alcohol outlets.
Self‐Administered Alcoholism Screening Test (SAAST): Comparison of Classificatory Accuracy in Two Cultures
Authors: Davis Leo J. , de la Fuente Juan‐Ramón , Morse Robert M. , Landa Eric , O'Brien Peter C.
Published: April 2006

Results of stepwise discriminant analyses of the Self‐Administered Alcoholism Screening Test (SAAST) administered to 181 alcoholics and 123 nonalcoholics in Mexico City were compared with results of a similar analysis of a sample in the United States (Rochester, MN). With sensitivities of 90% and 95%, specificities were 91.1% to 99.2% in the Mexican sample for total score and a nine‐item version developed on the Rochester sample. A new nine‐item version derived from the Mexican sample gave specificities between 95.1% and 99.2% at 90% and 95% sensitivities, as with the Rochester sample. The two items with greatest predictive power were the same in both cultures.
Ethanol Patch Test—A Simple and Sensitive Method for Identifying ALDH Phenotype
Authors: Murarnatsu Taro , Higuchi Susumu , Shigernori Kenji , Saito Masayoshi , Sasao Mitsuo , Harada Shoji , Shigeta Yosuke , Yamada Koichi , Muraoka Hideo , Takagi Satoshi , Maruyarna Katsuya , Kono Hiroaki
Published: April 2006

The ethanol patch test, which is considered to be a cutaneous model of flushing, was performed on 311 healthy Japanese (237 adults and 74 children). By comparing the results with aldehyde dehydrogenase (ALDH) phenotype determined by isoelectric focusing from hair root samples, it was demonstrated that the ethanol patch test is a good indicator of the ALDH phenotype. The usefulness of this test in future studies was discussed.
Effect of Ethanol and Vitamin B6 Deficiency on Pyridoxal 5‐Phosphate Levels and Fetal Growth in Rat
Authors: Lin Grace W‐J.
Published: April 2006

The effects of chronic ethanol consumption and dietary vitamin B6 levels on tissue pyridoxal 5‐phosphate (PLP) contents and rat fetal development were investigated. Pregnant Sprague‐Dawley rats were given 35% ethanol‐calorie liquid diet with either adequate B6 (1.7 mg/liter) or deficient B6 (0.17 mg/liter), ad libitum, from gestation days 7 to 21. Control groups (adequate control and deficient control) were pair‐fed with isocaloric sucrose substituted for ethanol. Rats were killed on gestation day 21. Ethanol groups had smaller fetuses than control groups, regardless of their dietary B6 levels. However, in B6 deficiency, ethanol affected fetal weight more severely than in B6 adequate state. Tissue PLP levels were determined by radioen‐zymatic method. In B6 deficiency, ethanol feeding reduced maternal liver PLP by 22%. PLP in other tissues were not affected by ethanol. These results confirmed that chronic alcohol consumption affected fetal growth and also provided evidence that B6 deficiency exacerbated ethanol effect.
Effects of Chronic Alcoholism on Perception of Hierarchical Visual Stimuli
Authors: Kramer Joel H. , Blusewicz Matthew J. , Robertson Lynn C. , Preston Ken
Published: April 2006

Visuospatial processing in chronic alcoholism was investigated by asking subjects to make similarity judgements of hierarchically constructed visual stimuli. Comparison figures were similar to a standard figure at the global or local level. Alcoholics were less influenced by the global patterns in their similarity judgements than were controls. On the WAIS‐R Block Design subtest, alcoholics were also more likely than controls to distort the outer configuration of the design. Results indicate that alcoholism affects global processing on both experimental visuoperception tasks and on clinical measures of visuospatial ability. Implications for models of alcoholic dysfunction are discussed.
Responses by Sons of Alcoholic Fathers to Alcoholic and Placebo Drinks: Perceived Mood, Intoxication, and Plasma Prolactin
Authors: Moss Howard B. , Yao Jeffrey K. , Maddock John M.
Published: April 2006

Young adult sons of alcoholic fathers (HR) were compared with matched young men from families without alcoholic relatives (LR) with respect to perceived mood, perceived intoxication, and plasma prolactin responses to oral challenge with two doses of alcohol and a placebo drink. HR subjects were found to have a qualitatively and quantitatively different mood response than controls to all three beverage conditions. HR subjects endorsed greater tension, depression, and fatigue across beverage conditions independent of alcohol dose. Alcohol dose interacted with risk status for perceived anger, vigor, and confusion. HR subjects reported less perceived intoxication on the descending limb of the alcohol concentration‐time curve across all three conditions. These differential responses could not be explained by the occurrence of personality subtypes determined through administration of the Tridimensional Personality Questionnaire. A significantly reduced prolactin response to alcohol in HR subjects could not be confirmed. Perceived mood effects of alcohol could have etiological significance in the development of alcoholism among HR individuals.
Sensitivity to the Anticonvulsant Effects of Ethanol and Pentobarbital in Mouse Lines Genetically Selected for Ethanol Sensitivity
Authors: Crabbe John C. , Belknap John K. , Young Emmett R.
Published: April 2006

Mouse lines genetically selected for susceptibility [long sleep (LS)] or resistance [short sleep (SS)] to the acute hypnotic effects of ethanol were tested for sensitivity to maximal electroshock seizures. LS mice were slightly more sensitive than SS mice. Ethanol or pentobarbital pretreatment elevated seizure thresholds in both lines. LS and SS mice were approximately equally protected by ethanol, but LS mice were somewhat more protected than SS mice by pentobarbital. These studies do not provide evidence that sensitivity to the anticonvulsant effect of ethanol is mediated by substantially the same genes as those mediating sensitivity to EtOH's hypnotic effects. However, sensitivity to pentobarbital's anticonvulsant effects may be genetically correlated.
Alcohol Withdrawal Syndrome: Clinical and Hormonal Responses to α2‐Adrenergic Agonist Treatment
Authors: Cushman P. , Sowers J. R.
Published: April 2006

Lofexidine (L) was compared to placebo (P) in a random double blind placebo controlled study of 23 healthy alcoholics in withdrawal. In serial alcohol withdrawal syndrome (AWS) scales, P ≥ L for first 18 hr. The major changes in AWS were in blood pressure and pulse, while restlessness or diaphoresis did not show faster normalization with L vs. P. Other ratings of withdrawal intensities and craving by patients were similar in both P and L. There were no differences in the rate of patient completion, or appearance of hallucinations by group. Plasma catecholamines were in the high ranges, similar in both groups at 0 and 3 hr, but after 5 hr P ≥ L for norepinephrine (but not epinephrine or dopamine). The data suggest L has pharmacological effects on some objective, catecholamine related, components of alcohol withdrawal, with little effect on others. L type treatment of alcoholics in withdrawal is promising, modestly effective and warrants further study.
Effect of Acute Ethanol on Uptake of [3H]Adenosine by Rat Cerebellar Synaptosomes
Authors: Clark Mike , Dar M. Saeed
Published: April 2006

Many classes of CNS‐acting drugs have been suggested to act at least partially via inhibition of adenosine uptake. Synaptosomal uptake of [3H] adenosine and the effect of acute ethanol on it were studied in a rat brain area known to be involved in the coordination and modulation of normal motor activity, the cerebellum. Uptake of [3H] adenosine was found to be linear with time (about 40 sec) and increasing concentrations (up to 1.5 μM) of adenosine. The uptake of [3 H] adenosine was inhibited by dilazep (IC50= 2.5 × 10‐7 M) in a dose‐dependent manner. Pharmacologically and/or toxicologically relevant concentrations of ethanol (2.5 to 100 mM) significantly inhibited the uptake of [3 H] adenosine between 12 and 15%. Lineweaver‐Burk plots indicated that both in vitro (25 mM) and in vivo (1.5 g/kg i.p.; 30 mM blood level) ethanol lowered Km as well as Vmax. values for adenosine uptake to nearly the same extent. In the case of in vivo ethanol, no ethanol was present during the assay since synaptosome preparation would wash out residual ethanol. The results of the present study indicate possible membranal alterations by in vivo ethanol. It is concluded that the uptake of [3 H] adenosine is inhibited by intoxicating concentrations of ethanol in vitro and by acute ethanol (1.5 g/kg) in vivo. This may partially explain the modulatory role of endogenous adenosine in ethanol‐induced motor disturbances.
Ethanol Reinforcement in the Alcohol Nonpreferring Rat: Initiation using Behavioral Techniques without Food Restriction
Authors: Samson H. H. , Tolliver G. A. , Lumeng L. , Li T‐K.
Published: April 2006

Genetic selection of rats can markedly alter their ethanol consumption. The manner in which environmental factors interact in these genetically selected animals to influence ethanol consumption has not been thoroughly investigated. Using the alcohol‐nonpreferring (NP) line of rats selectively bred at the Indiana University School of Medicine, alcohol self‐administration in an operant situation was initiated using either a sucrose‐fading or a secondary‐conditioning procedure. These initiation procedures do not require any food or fluid restriction. Initiation was successful in 10 out of 12 NP animals, with the initiated rats self‐administering ethanol at concentrations as high as 40%. Following initiation, a retest of home‐cage ethanol preference found increases in ethanol acceptability. When tested in a concurrent operant situation, the initiated NP rats also chose ethanol over water. However, the NP rats had lower alcohol intakes and a different pattern of drinking over time when compared to that of nonselected Long‐Evans rats. While the NP rats could be initiated to lever‐press for ethanol, at no time did their intake approach that of the selected line of alcohol‐preferring (P) rats. Thus, while an upward shift from the genetic baseline in ethanol preference and intake can result from the environmental initiation manipulations employed in these studies, genetic factors would appear to limit the extent to which ethanol ingestion can be increased.
Psychophysiological Effects of Alcohol‐related Stimuli: II. Enhancement with Alcohol Availability
Authors: Turkkan Jaylan S. , McCaul Mary E. , Stitzer Maxine L.
Published: April 2006

This laboratory study examined methods of enhancing physiological and subjective responses of alcoholics to naturalistic alcohol‐related stimuli by repeated exposures to a high‐dose alcohol drink. Individual subjects participated in five successive daily sessions consisting of randomized‐block presentations of gustatory and visual presentation of alcohol, pepper juice (as a control for stimulus taste intensity), or water stimuli. Following the stimulus trial series, all subjects ingested 1.5 oz of alcohol in a shot glass. Twelve subjects next received a 1.7 g/kg alcohol drink (“high dose alcohol group”) on Days 1‐4 and placebo on Day 5, and 12 subjects received a placebo drink on all study Days (1‐5) (“placebo drink group”). On Day 1, alcohol stimuli generally elicited larger heart rate and skin conductance increases and skin temperature decreases than water or pepper juice stimuli. Alcohol stimuli also elicited greater subjective responses than either pepper juice or water. Alcohol availability within the taste trial markedly increased physiological and subjective reactivity to alcohol‐related stimuli, perhaps due to the closer approximation to natural drinking behavior. A comparison with previous data from this laboratory suggests that prestudy deprivation from alcohol, instructions to expect alcohol, a conducive drink setting, and the opportunity to drink alcohol within the session may enhance reactivity to alcohol stimuli in alcoholics.
Chronic Tolerance to Ethanol in the N:NIH Rat
Authors: Grant Kathleen A. , Werner Robert , Hoffman Paula L. , Tabakoff Boris
Published: April 2006

As the basis for selectively breeding rats from the N:NIH stock on the basis of differential development of tolerance to ethanol, chronic tolerance to the motor‐disrupting effects of ethanol was examined. Male (n= 50) and female (n= 46) rats were administered 2.5 g/kg ethanol (i.p.) and the blood‐ethanol concentration (BEC) at the time of regain of aerial righting reflex (RARR) was measured. The rats were then placed in inhalation chambers for 8 consecutive days and chronically exposed to ethanol. Thirty‐two hours following the cessation of chronic ethanol exposure, the rats were again given a 2.5 g/kg dose of ethanol and the BEC at RARR was again measured. The amount of chronic ethanol tolerance developed, as measured by the difference in BEC at RARR prior to and after chronic ethanol administration, was widely and normally distributed for both male and female rats. Control rats, which did not receive chronic ethanol exposure between the two tests of RARR, did not show tolerance on this measure. A negative correlation (r= ‐0.46) was found between BEC at RARR prior to chronic ethanol treatment and the amount of chronic tolerance developed using the difference in BEC measure. This correlation suggested that the rats who were initially more sensitive to the effects of ethanol were more likely to display the greatest amount of chronic tolerance. However, using the residuals of the regression analysis of post‐chronic ethanol BEC at RARR on prechronic BEC at RARR as an index of tolerance, this negative correlation was not found. Thus, while the difference scores may be appropriate for chosing individuals to breed in a selection study, it appears that using a difference score to assess the development of tolerance could lead to an incorrect assessment of the relationship between initial sensitivity and tolerance.
Ethanol Administration Diminishes the Endotoxin‐induced Increase in Glucose Metabolism
Authors: Molina Patricia E. , Lang Charles H. , Bagby Gregory J. , D'Souza Nympha B. , Spitzer John J.
Published: April 2006

The metabolism of ethanol (ETOH) is known to increase the cytosolic NADH/NAD ratio and consequently impairs hepatic glucose output in the fasted state. In contrast, one of the characteristic alterations in glucose metabolism produced by the administration of endotoxin is an increase in the de novo synthesis of glucose. Therefore, the present study tests the hypothesis that the acute administration of ETOH will prevent the endotoxin‐induced increase in glucose production. In vivo glucose kinetics were determined by the infusion of [6‐3H, U‐14C]glucose in catheterized conscious rats. The intravenous infusion of tracer glucose, and ETOH (100 mg/100 g b.w./hr) or saline were started at the same time and both continued throughout the experiment. Two hours later the ETOH infusion rate was decreased to maintain the Mood ETOH levels between 100 and 160 mg/dl. At 140 min, endotoxin (100 μg/100 g b.w.) was injected. ETOH alone did not alter basal values of plasma glucose (5 mM), glucose rate of appearance (Rs; 35 μmol/min/kg) or metabolic clearance (MCR; 7 ml/min/kg). Endotoxin alone increased plasma glucose (80X) and lactate (140%) concentrations, glucose Rs (60K) and recycling (40%) in saline‐infused rats, whereas in ETOH‐infused animals, plasma glucose and lactate levels were only elevated 40% and glucose Rs and recycling were unchanged. The results show that acute ETOH administration diminishes the increased glucose production and utilization seen in endotoxemia. The attenuation of the endotoxin effect by ethanol is due to inhibition of hepatic glucose production and peripheral glucose utilization.
In Vivo Effect of Chronic Ethanol Abuse on Membrane αl‐Glycoprotein of Lymphocytes and Immune Response to Various Stimulating Agents
Authors: Stefanini G. F. , Mazzetti M. , Zunarelli P. , Piccinini G. , Amorati P. , Capelli S. , Cicognani G. , Gasbarrini G.
Published: April 2006

Data on the immune status of chronic alcoholic patients are rather conflicting probably due to the interference of liver disease and/or malnutrition on immune function. In order to avoid this kind of interference, peripheral lymphocytes from 12 chronic alcoholic patients in good nutritional status and without heavy liver damage and 15 healthy controls were examined in this study. Lymphocyte functional activity was evaluated by means of response to phytohemagglutinin, calcium ionophore A 23187, and autologous non‐T‐cells [autologous mixed lymphocyte reaction (AMLR)]. Phenotypical analysis was carried out by the indirect immunofluorescence technique using monoclonal antibodies specific to CD5 (mature T‐lymphocytes). CD4 (helper/inducer T‐lymphocytes), CD8 (suppressor/cytotoxic T‐lymphocytes), glycoproteins, and an immunoglobulin fraction from rabbit directed to membrane α1 acid glycoprotein (AGP) that is involved in T‐cell activation process.

Our results show significant impairment in AMLR while response to phytohemagglutinin, heterologous non‐T‐cells and carcinoma ionophore did not differ from controls. No differences were present in circulating T‐lymphocytes expressing CD5, CD4, and CD8 on their membrane, whereas AGP‐bearing lymphocytes were significantly lower in chronic alcoholics (14.4 ± 8.6) than in controls (31.9 ± 8.1; p < 0.001). These results support the hypothesis of a direct action of alcohol on one of the pathways of lymphocyte activation and the role of the lymphocyte membrane AGP on the AMLR.
Ethanol and Soluble Mediators of Host Response
Authors: Roselle Gary A. , Mendenhall Charles L. , Grossman Charles J.
Published: April 2006

Lymphokines serve to modulate host inflammatory response by providing a communication link among cells involved in resistance to infection. In the alcoholic, this system may be impaired due to a combination of the direct effects of ethanol on immunocompetent cells and the soluble factors involved in cell‐cell interactions. In this paper, we review the literature on this subject, describe an ethanol‐related impairment of migration inhibitory factor activity in the rat, and present a possible mechanism for this alteration.
Are Special Treatment Facilities for Female Alcoholics Needed? A Controlled 2‐Year Follow‐up Study from a Specialized Female Unit (EWA) Versus a Mixed Male/Female Treatment Facility
Authors: Dahlgren Lena , Willander Anders
Published: April 2006

Women with alcohol problems constitute an increasing number of patients in medical service. Do they need special care? How should the treatment program be designed?

The specialized female Karolinska Project for Early Treatment of Women with Alcohol Addiction (EWA) unit at the Karolinska Hospital in Stockholm, Sweden, was opened in 1981. The aim of the project is to reach women in an early stage of alcohol dependence behavior and to develop treatment programs specific to the needs of females alone.

In order to investigate the value of such a specialized female unit a controlled 2‐year follow‐up study was carried out including 200 women. The probands were treated in the female only EWA‐unit, whereas the controls were placed in the care of traditional mixed‐sex alcoholism treatment centers.

The 2‐year follow‐up study showed a more successful rehabilitation regarding alcohol consumption and social adjustment for the women treated in the specialized female unit (EWA). Improvement was noted also for the controls but to a lesser extent. Probably one of the most important achievements of a specialized female unit, such as EWA, is to attract women to come for help earlier.
Risk for Hypertension in Female Members of Multigenerational Male‐Limited Alcoholic Families
Authors: Miller Sydney B. , Finn Peter R. , Ditto Blaine , Pihl Robert O.
Published: April 2006

Cardiovascular hyperreactivity to psychological stress has been implicated as a risk factor for cardiovascular disease. Recent reports have suggested that male off spring of multigenerational male‐limited alcoholic families display cardiovascular hyperreactivity to stress. Data concerning cardiovascular disease in 371 individuals from multigenerational male‐limited alcoholic families and other family types of differing risk for alcoholism were subjected to χ2 analyses. Results indicated a significantly greater incidence of hypertension in female members of multigenerational male‐limited alcoholic families as compared to the other family types.
Magnetic Resonance Imaging of the Brain in Alcoholics: Cerebral Atrophy, Lifetime Alcohol Consumption, and Cognitive Deficits
Authors: Chick J. D. , Smith M. A. , Engleman H. M. , Kean D. M. , Mander A. J. , Douglas R. H. B. , Best J. J. K.
Published: April 2006

Magnetic resonance imaging of the brain in 69 detoxified alcoholics revealed that relaxation time (T1) in whole brain and in grey matter and parietal white matter was greater than in age‐matched controls. In 48 patients, data on cognitive function and lifetime alcohol consumption were available. With age‐controlled, lifetime consumption, and impairment on performance in the cognitive test (a Category Sorting Test) correlated positively withT1in whole brain and in selected regions. Impairment in the cognitive test correlated with increasedT1in whole brain and white matter independently of cerebral atrophy. Alcohol consumption patterns in the following 6 months were unrelated to changes inT1. The excess water implied by the elevatedT1values may be intra‐ or extracellular. It is uncertain whether or notT1elevation in alcoholics is a marker of neuronal damage.T1elevation appears to be a marker of one type of alcohol‐related cognitive impairment.
Effect of Alcohol on Blood Dolichol Concentration
Authors: Roine Risto P. , Nykänen Irma , Ylikahri Reino , Heikkilä Juha , Suokas Antti , Salaspuro Mikko
Published: April 2006

Serum dolichol levels were studied in 95 active alcoholics and 16 abstinent alcoholics (at the time of blood sampling) and compared to those of 41 social drinkers. Active alcoholics had a significantly higher mean serum dolichol concentration (182.7 ± 5.1 ng/ml, p < 0.001 than either abstinent alcoholics (138.7 ± 5.4 ng/ml) or social drinkers (142.1 ± 4.1 ng/ml). During weekend (48 hr) heavy drinking (5.5 g of alcohol per kg b.w.) no significant changes were seen in mean serum dolichol concentrations in 10 healthy, nonalcoholic volunteers. Neither did moderate drinking for 10 days (60 g of alcohol daily)—preceded and followed by a period of abstinence—produce any significant changes in serum dolichol levels in 10 nonalcoholic subjects.

During detoxification treatment of 12 alcoholics, mean serum dolichol concentration stayed constant for the first 7 days; on entering treatment it was 227.7 ± 15.0 ng/ml, on the 3rd day 238.5 ± 15.9 ng/ml, and on the 7th day of treatment 222.6 ± 18.6 ng/ml.

Our results show that as well as increasing urinary dolichol excretion, chronic alcohol abuse also produces increased serum dolichol concentrations. However, contrary to urinary dolichols, serum dolichol levels do not react significantly to heavy drinking lasting for 48 hr in nonalcoholic volunteers. Furthermore in alcoholics increased serum dolichol concentrations do not decrease as rapidly during abstinence as urinary dolichol concentrations do.
Human Neutrophils Are Not Severely Injured in Conditions Mimicking Social Drinking
Authors: Corberand J. X. , Laharrague P. F. , Fillola G.
Published: April 2006

In an attempt to assess the effect of alcohol per se on human polymorphonuclear neutrophils (PMN), irrespective of other physiopathological parameters, we examined neutrophil function in healthy volunteers who had taken a single large dose of whisky. Before and at different times after ingestion, several PMN properties were simultaneously tested including random migration, in vitro chemotaxis, adherence, aggregation, cytochrome C reduction, phagocytosis, bacterial killing, intracellular CAMP and cGMP contents, myeloperoxidase, and neutrophil alkaline phosphatase scores. Only phagocytosis of Staphylococcus aureus was significantly depressed after alcohol ingestion. Adherence was inhibited only in some individuals when their respective blood alcohol levels were the highest. Both alterations were moderate and reversible.

These data point out the limited effect of occasional alcohol consumption on the different facets of neutrophil behavior. These findings suggest that factors other than alcohol itself could be concerned in the marked PMN dysfunction well established in chronic alcoholism.
Effects of Acute Ethanol Administration on Stimulated Parotid Secretion in the Rat
Authors: Scott J. , Berry M. R. , Woods K.
Published: April 2006

Young adult male rats previously never exposed to ethanol were given a single dose of 4 ml of 35% (v/v) ethanol in water by direct intragastric intubation (approximate weight related dose = 5.2 g/kg). Control rats were given distilled water in the same volume by the same route or were given no intragastric fluids. After administration of Valium‐Hypnorm anesthesia, parotid salivary secretion was stimulated by subcutaneous pilocarpine HCl (10 mg/kg), and accurately timed samples were collected. No differences were recorded in the rate of salivary flow during the initial (5‐min) high‐flow phase of secretion, but during the subsequent 25‐min phase of secretion the output in ethanol‐treated rats was depressed by 60% compared to controls (p < 0.01). Furthermore, electrolyte analyses of this saliva indicated that salivary ductal resorptive activity might be diminished in the presence of high blood ethanol. However, when rats were previously habitually exposed to ethanol at a twice daily dose of 4 ml of 35% (v/v) ethanol in water, the inhibitory action of acute ethanol administration was abolished. Moreover, in these rats there was significantly depressed [Na+] in both high‐flow and low‐flow saliva samples (p < 0.01) with little change in [Na+] occurring at higher flow rates. This suggests the possibility of enhanced ductal resorption developing in rats exposed to long‐term ethanol feeding.
Evaluation of Carbohydrate‐deficient Transferrin Compared with Tf Index and Other Markers of Alcohol Abuse
Authors: Schellenberg F. , Bénard J. Y. , Le Goff A. M. , Bourdin C. , Weill J.
Published: April 2006

If has been known for some years that a partial deglycosylation of transferrin occurs in the sera of alcohol abusers. Different methods have been proposed in order to evaluate this carbohydrate‐deficient fraction of serum transferrin. Chromatofocusing or isoelectric focusing followed by direct immunofixation have been used until now. Recently, a new method called the carbohydrate‐deficient transferrin (CDT) test based on ion‐exchange chromatography has been developed by Stibler et al. (Alcohol Clin Exp Res 10:535–544, 1986). Here we compare this new method with results obtained using our Tf Index determination method. The upper limit of normal values was set to the 90th percentile of the values observed in a reference population. The population under investigation consisted of 50 healthy volunteers and 160 alcohol abusers whose ethanol consumption was evaluated through a questionnaire. Sensitivity and specificity of the CDT test have been found higher than 0.76 and 0.90, respectively. The correlation between both methods was 0.794, a satisfactory result considering that the CDT test and the Tf index do not exactly measure the same part of the carbohydrate‐deficient transferrin. In a population of 23 patients with liver diseases not related to alcohol abuse, no abnormal CDT value was observed. We can conclude from these results that the CDT test now seems to be die best test to detect alcohol abusers.
Characterization of the Increased Binding of Acetaldehyde to Red Blood Cells in Alcoholics
Authors: Hernández‐Muñoz Rolando , Baraona Enrique , Blacksberg Ilene , Lieber Charles S.
Published: April 2006

Using equilibrium dialysis, we found that acetaldehyde, at the levels commonly occurring after ethanol ingestion, did not bind detectably to plasma proteins, but there was significant binding to red blood cells, more in alcoholics than in nonalcoholics. The binding to red blood cells was inhibited by pyridoxal phosphate and N‐ethylmaleimide, suggesting adduction to amino and thiol groups. Binding kinetics were consistent with at least two sites. The one with the highest affinity for acetaldehyde corresponded to hemoglobin. Its affinity and mMAX were not changed in alcoholics, but these binding sites accounted for only 44% of the sites available in the red blood cells of alcoholics and 80% of those in controls. Moreover, this binding was not inhibited by W‐ethylmaleimide. There was no detectable binding to red cell ghosts. Nonprotein binding was then assessed by changes in NADH produced by the addition of protein‐free fractions of the cells to an alcohol dehydrogenase system in equilibrium; this revealed a second binder of lower affinity, larger capacity and with sensitivity to both inhibitors. This binding (possibly due to thiazolidine formation with cysteine) was enhanced in alcoholics, whose red blood cell cysteine content was doubled. Levels of red blood cell cysteine and acetaldehyde remained high for 2 weeks after withdrawal. Because of the prolonged persistence after withdrawal, these changes may provide new markers of alcoholism.
Ethanol Teratogenesis in Selectively Bred Long‐Sleep and Short‐Sleep Mice: A Comparison to Inbred C57BL/6J Mice
Authors: Gilliam David M. , Kotch Lori E. , Dudek Bruce C. , Riley Edward P.
Published: April 2006

Sensitivity to alcohol may influence the severity of ethanol teratogenesis. To examine this hypothesis, the teratogenic effects of ethanol were compared in Long‐Sleep (LS) and Short‐Sleep (SS) mice, selectively bred for differences in ethanol‐induced narcosis. Inbred C57BL/6J (B6) mice were included to confirm previously reported teratogenic effects using our own treatment regimen and standard assessment techniques. Intragastric administration of ethanol (5.8 g/kg) on Days 9 and 10 of pregnancy resulted in growth retardation and an increase in prenatal mortality in LS litters but not in SS litters. Therefore, alcohol sensitivity plays a role in the severity of prenatal alcohol effects. B6 mice showed more ethanol teratogenicity than either LS or SS mice, even though maternal blood ethanol levels were similar across genotypes. This result suggests genetic variations other than alcohol sensitivity also influence ethanol teratogenesis.
An Analysis of Postmortem Brain Samples from 32 Alcoholic and Nonalcoholic Individuals for Protein III, a Neuronal Phosphoprotein
Authors: Grebb Jack A. , Browning Michael D. , Valverius Peter , Borg Stefan , Sedvall Göran , Greengard Paul
Published: April 2006

Protein phosphorylation is a primary mechanism of intracellular signal transduction, and abnormalities in protein phosphorylation have been implicated in the pathogenesis of several specific diseases. Protein III is a neuronal phosphoprotein that is associated with synaptic vesicles and is probably involved in the regulation of neurotransmitter release. Analysis of 32 postmortem brains has confirmed our previous report that variant forms of protein III with higher apparent molecular weights are found frequently in the brains of alcoholic individuals but rarely In the brains of nonalcoholic individuals who did not suffer from any other medical or neuropsychiatric disorders. Eight of 14 (57%) brain samples from alcoholic individuals and four of eight (50%) brain samples from suspected alcoholic individuals had variant forms, while none of 10 samples from nonalcoholic individuals had variant forms. Previous data indicate that variant forms of protein III are also associated with other neurodegenerative conditions, including various dementias, and, possibly, normal aging.
A Comparison of Ethanol Partitioning in Biological and Model Membranes: Nonideal Partitioning is Enhanced in Synaptosomal Membranes
Authors: Sarasua Martha M. , Faught Karla R. , Steedman Susan L. , Gordin M. Daniel , Washington M. K.
Published: April 2006

The partitioning of ethanol into mouse brain synaptosomes at 37°C was characterized as a function of ethanol concentration. In addition, the partitioning of ethanol into multilamellar dipalmitoylphosphatidylcholine (DPPC) vesicles was characterized as a function of ethanol concentration and temperature. DPPC liposomes provided a model for ethanol partitioning into a phospholipid bilayer of defined composition allowing comparison to the more complex synaptosomal membrane.

The values of the partition coefficients for ethanol depend on the convention used to express concentration in the partition coefficient ratio. We express these concentrations as mole fractions of ethanol in the membrane and aqueous phases.

Ethanol partitioning is nonideal (ethanol membrane: buffer partition coefficients vary with total ethanol concentration). In synaptosomes, the partition coeffients vary markedly with concentration and asymptotically approach zero at higher concentrations. In the DPPC system, the variation of the partition coefficient is less pronounced, but significant. The ethanol: DPPC partition coefficients decrease by a factor of 2 at ethanol concentrations above 3.2 × 10‐3 M. This suggests a model involving at least two distinguishable types of interactions of ethanol with the membrane. Ethanol appears to undergo both bulk phase partitioning into the membrane bilayer core and nonspecific binding to the membrane surface. In pure DPPC, bulk phase hydrophobic partitioning predominates. In synaptosomes, nonspecific surface binding appears to be a major interaction.

Temperature studies indicate ethanol partitioning into DPPC increases above the phospholipid gel to liquid crystalline phase transition temperature. This suggests a preferred partitioning of ethanol into fluid state lipid. However, significant membrane concentrations of ethanol are found in gel state DPPC.
Differences in the Nature and Kinetics of the Ethanol‐related Circulating Cytotoxic Proteins in Normal Subjects and Patients with Alcohol‐induced Cirrhosis
Authors: Wickramasinghe S. N. , Clague J. R. , Barrison I. G. , Walker J. G. , Barden G. , Gardner B.
Published: April 2006

The kinetics and nature of the nondialyzable cytotoxic activity which appeared in the serum after the consumption of 1.2 g ethyl alcohol per kilogram body weight over 45 min was studied in six healthy volunteers and eight patients with histologically proven alcohol‐related cirrhosis of the liver. Whereas the cytotoxic activity in the dialyzed serum showed a single peak with a maximum value 8 hr after the start of ethanol consumption in the healthy volunteers, it showed two peaks with maximum values at 2 and 8 hr in the patients with cirrhosis. Studies of the fractions obtained by Sephacryl‐S‐300 gel filtration of the 2‐hr postalcohol serum samples revealed substantial cytotoxic activity in the fractions containing both the albumin peak and the IgG peak in the patients with cirrhosis and only in the fractions containing the albumin peak in the healthy volunteers. Experiments with pure IgG preparations obtained from prealcohol and 2‐hr postalcohol sera by chromatography on Q‐Sepharose Fast Flow anion‐exchange resin showed considerable cytotoxic activity in the preparations from the patients with cirrhosis and little or no cytotoxic activity in those from the healthy volunteers. Thus, the early peak of the biphasic serum cytotoxicity curve seen after ethanol consumption by patients with cirrhosis appeared to be caused by the development of a substantial cytotoxic activity in the IgG molecules during the first 2 hr. When prealcohol sera from healthy subjects and patients with cirrhosis were incubated with various concentrations of [14C]acetaldehyde at 37°C for 6 hr, and the reacted sera were dialyzed and subjected to gel filtration, the proportion of radioactivity associated with the IgG peak was found to increase progressively with increasing concentrations of [14C]acetaldehyde. It therefore appeared that the differences in the nature and kinetics of the cytotoxic proteins which circulate after ethanol consumption in healthy subjects and patients with cirrhosis may be due to the generation of higher levels of blood acetaldehyde in the latter. The differences may also be partly related to the increased serum IgG levels and the reduced serum albumin levels often seen in alcohol‐induced cirrhosis.