bluuebunny/crossref_metadata_2025 huggingface dataset:
Severity of Alcohol Dependence and Social/Occupational Problems: Relationship to Clinical and Familial History
Authors: Hasin Deborah S. , Grant Bridget F. , Endicott Jean
Published: April 2006

We examined the relationship of major depression, aspects of antisocial personality disorder, family history of alcoholism, treatment history, and onset of alcohol problems to the severity of alcohol dependence and severity of social/occupational problems due to alcohol. Subjects were 111 randomly sampled patients in alcohol rehabilitation. The predictor variables formed different patterns of relationships with alcohol dependence and with social/occupational problems. Implications of the findings for future research are discussed.
Effects of Malotilate on Alcoholic Liver Injury in Rats
Authors: Matsuda Yoshiro , Takada Akira , Yasuhara Minoru , Sato Hiroyuki
Published: April 2006

Malotilate (diisopropyl 1,3‐dithio‐2‐yldenemalonate), a hepatotrophic drug, was administered to rats with alcohol‐pyrazole hepatitis, which is considered to be a suitable experimental model for alcoholic liver injury, in order to elucidate the effects of malotilate on alcoholic liver injury. The number of ballooned hepatocytes and necrotic hepatocytes were smaller in the alcohol‐pyrazole hepatitis rats treated with malotilate for 12 weeks (Al‐Py Mal group) than for those without malotilate treatment (Al‐Py group). Immunohistochemically, the retention of transferrin, one of the secretory proteins from the liver, in the ballooned hepatocytes was inhibited by malotilate. Biochemically, transferrin content in the Golgi fraction of the hepatocytes was significantly lower in the Al‐Py Mal group than in the Al‐Py group. Hepatic acetaldehyde levels in the Al‐Py Mal group were significantly lower than those in the Al‐Py group, even though ethanol metabolic rates were not different between the two groups. These results indicated that malotilate prevented the development of hepatocytic injury in alcohol‐pyrazole hepatitis by decreasing hepatic acetaldehyde levels and preventing the retention of transferrin in the hepatocytes.
Alcohol‐related Symptoms in Heterogeneous Families of Hospitalized Alcoholics
Authors: Gilligan Sheila B. , Reich Theodore , Robert Cloninger C.
Published: April 2006

Heterogeneity in the clinical symptoms of alcohol abuse was examined in 243 men and 305 women from families of hospitalized alcoholics, who had demonstrated different patterns of inheritance of susceptibility to alcoholism. Discriminant analysis was utilized to identify nine alcoholic symptoms that distinguished male relatives of alcoholic men from those of alcoholic women. Inability to abstain from alcohol, fighting and reckless driving while intoxicated, and alcohol treatment other than Alcoholics Anonymous were more prevalent in families of male probands. Male relatives of female probands experienced later onset of loss of control over drinking associated with benders, and cirrhosis and feelings of guilt. Female relatives of alcoholic men and women showed a marked predominance of the latter (Type 1) features, whereas male relatives had different clinical features, depending on the associated mode of inheritance.
Harman in Alcoholic Beverages: Pharmacological and Toxicological Implications
Authors: Bosin Talmage R. , Faull Kym F.
Published: April 2006

Harman, a β‐carboline compound, was identified and quantitated in beer and wine samples using a combination of high performance liquid chromatography with fluorescence detection and gas chromatography‐negative chemical ionization mass spectrometry. The concentration of harman in beer (7.3–140.0 ng/ml) was greater than in wine (0.8–10.5 ng/ml) and was not related to alcohol content. The pharmacological and toxicological implications of harman in alcoholic beverages are discussed.
Opiate Antagonist Nalmefene Inhibits Ethanol‐induced Flushing in Asians: A Preliminary Study
Authors: Ho Samuel B. , DeMaster Eugene G. , Shafer Rex B. , Levine Allen S. , Morley John E. , Go Vay Liang W. , Allen John I.
Published: April 2006

Ethanol‐induced flushing (EIF) occurs in up to 80% of Asians and is characterized by facial flushing, tachycardia, and increased cardiac output. Since endogenous opiates and prostaglandins may be mediators of flushing syndromes, we attempted to block EIF in four Asian flushers with single doses of either the opiate antagonist nalmefene, or the prostaglandin synthesis inhibitor indomethacin. Nonflushers (2 Caucasian, 2 Asian) and four Asian flushers were given on separate days water, ethanol (0.4 g/kg p.o.), ethanol plus nalmefene (2 mg i.v.), or ethanol plus indomethacin (50 mg p.o.). Ethanol concentrations of flushers and nonflushers were similar. Mean (±SEM) plasma acetaldehyde concentrations of flushers (28.2 ± 11.8 μM) were significantly greater than nonflushers (1.4 ± 0.5 μM) following ethanol ingestion (p < 0.001). Ethanol alone always induced a significant rise in facial skin temperature [mean area under the curve (AUC) = 5142 ± 648 %ΔT± min, p < 0.01] and of pulse (mean AUC = 1622 ± 120 bpm ± min, p < 0.001) in flushers compared to water ingestion. A single dose of nalmefene (2 mg i.v.) but not indomethacin (50 mg p.o.), reduced the mean (±SEM) ethanol‐in‐duced rise in facial skin temperature of flushers by 58 ± 14% (p < 0.05) without changing plasma acetaldehyde concentrations. These data are preliminary evidence that the opiate antagonist, nalmefene, blocks some of the vascular manifestations of EIF without altering the elevated plasma concentrations of acetaldehyde.
Mitochondria as the Primary Site of Acetaldehyde Metabolism in Beef and Pig Liver Slices
Authors: Na Cao Qing , Tu Guang‐Chou , Weiner Henry
Published: April 2006

Aldehyde dehydrogenase (ALDH) is the major enzyme involved in the oxidation of acetaldehyde. It has been shown that the liver enzyme is located in both cytosol and mitochondria. It has not been established where the subcellular oxidation of acetaldehyde occurs in species other than rat. Using slices isolated from beef and pig livers and selectively inhibiting the mitochondria enzyme with cyanamide or the cytosolic enzyme with disulfiram, it was possible to address this question. It was found that with both beef and pig liver slices 60% of the oxidation was catalyzed by the mitochondrial ALDH and 20% by the higher Km cytosolic enzyme. The remainder of the metabolism was the result of non‐ALDH involvement. Furthermore, any decrease in the level of the low Km mitochondrial aldehyde dehydrogenase activity resulted in a decreased rate of acetaldehyde oxidation showing that its activity governed the rate of acetaldehyde oxidation. These were the same conclusions previously reached using rat liver tissue slices. Thus, it appears that for all mammalian tissue, mitochondria is the primary location of acetaldehyde oxidation.
Effect of Alcohol on Glucose Tolerance in Normal and Noninsulin‐dependent Diabetic Subjects
Authors: Singh Sant P. , Kumar Yoginder , Snyder Ann K. , Ellyin Frederick E. , Gilden Janice L.
Published: April 2006

Oral glucose tolerance tests were conducted in 10 noninsulin‐dependent diabetic and 14 healthy control subjects with a 75‐g glucose load. The tests were repeated 1 week later with 43 g of ethanol mixed with the glucose. Blood samples were analyzed for ethanol, glucose, insulin, C‐peptide, and glucagon levels. The blood ethanol peak was nearly equal in diabetic and control subjects (mean ± SEM values of 55 ± 8 and 48 ± 6 mg/dl 45 min after ethanol ingestion). Ethanol did not affect glucose tolerance in either of the study groups. Mean ± SEM values of the sum of the increment above the baseline glucose level were 659 ± 48 vs. 675 ± 76 mg/dl with or without ethanol in diabetics and 227 ± 35 vs. 244 ± 36 mg/dl in control subjects. The plasma insulin and C‐peptide responses to glucose were delayed in diabetic patients compared to controls but were not affected by ethanol. In vitro, ethanol, at a concentration of 100 mg/dl or greater, significantly decreased insulin binding to erythrocytes in a dose‐related manner. Scatchard analysis of competitive insulin binding to erythrocytes indicated that ethanol reduced insulin binding affinity (1.6 ± 0.5 vs. 4.2 ± 0.8 x 108/M), but not binding capacity (4.5 ± 2.4 vs. 4.4 ± 1.7 nM, with and without ethanol, respectively).
Chronic Alcohol Ingestion Decreases Pituitary‐Thyroid Axis Measures in Fischer‐344 Rats
Authors: Mason Geroge A. , Stanley Donald A. , Walker Cheryl H. , Hashimoto Hiromichi , Noonan Linda R. , Prange Arthur J.
Published: April 2006

In a chronic feeding study adult male Fischer‐344 rats (n= 12) were fed a nutritionally complete liquid diet containing 10% (w/v) ethanol for 40 days while control animals (n= 12) were pair fed a nutritionally complete isocaloric diet in which dextrose was substituted for ethanol. Treated animals were gradually introduced to and withdrawn from the 10% diet. At the end of the study and at sacrifice ethanolfed rats had gained slightly more weight than pair‐fed controls. They also showed a significant decrease in total thyroxine, free thyroxine, L‐triiodothyronine, reverse L‐triiodothyronine, and basal thyroid‐stimulating hormone. These differences did not appear to result from caloric deprivation alone. Possible explanations for some of these thyroidal changes are discussed.
Risk for Alcoholism: A Comparison Between Two Different Groups of Sons of Alcoholics on Cardiovascular Reactivity and Sensitivity to Alcohol
Authors: Finn Peter R. , Pihl Robert O.
Published: April 2006

Two groups of sons of alcoholic fathers of differing family pedigrees for alcoholism [multigenerational (MGH) versus unigenerational (UGH)] were compared on measures of cardiovascular reactivity to unavoidable shock under alcohol and no alcohol consumption conditions. The MGH subjects were significantly more reactive than UGH subjects to the shock procedure on a measure of peripheral vasoconstriction (digital blood volume amplitude) with a similar trend on heart rate. The MGH subjects were significantly more sensitive to the reactivity dampening effects of alcohol than the UGH subjects on both cardiovascular measures. MGH subjects were also significantly more alexithymic than UGH subjects. The results are discussed in terms of the potential etiological significance of these characteristics in MGH males, and the importance of delineating the family history for at least two generations when assigning risk status to potential subjects.
Reduced IgG Fc‐Receptor‐mediated Phagocytosis in Human Monocytes Isolated from Alcoholics
Authors: Mørland Henning , MD Jon Johnsen , MD Anders Bjørneboe , Bjørneboe Gunn‐Elin Aa. , Drevon Christian A. , Mørland Jørg , PhD Berit Mørland
Published: April 2006

Blood monocytes (MC) were isolated from alcoholics and from agematched controls. Phagocytosis mediated by the IgG Fc‐receptor (Fc‐R) was assessed in the MC immediately after isolation by using IgG‐opsonized sheep erythrocytes as test particles. Experiments were also performed after preincubating the MC in medium containing 10% autologous serum with or without ethanol (80 mM) in vitro at 37°C for 15 min, and with or without ethanol (80 mM) present during the internalization assay in vitro (37°C for 60 min). MC from alcoholics exhibited lower phagocytic capacity via the Fc‐R than MC from healthy controls, approximately 50% versus 70% phagocytosing cells. Preincubation of the MC in medium containing 10% autologous serum with 80 mM ethanol, reduced the percentage of phagocytosing MC from controls to 55%, whereas no further reduction occurred in cells from alcoholics. When present during the assays of Fc‐R function, ethanol decreased MC phagocytosis of IgG‐coated particles significantly in both test groups, to about 30% phagocytosing cells. Blood samples disclosed increased serum levels of markers of liver dysfunction, immunoglobulins, increased sedimentation rate, and white blood cell counts among the alcoholics, while their serum levels of 1,25‐dihydroxyvitamin D3 were reduced.
Interaction of Stress and Ethanol: Effect on β‐Endorphin and Catecholamines
Authors: Patel Vandana A. , Pohorecky Larissa A.
Published: April 2006

To examine the interaction of ethanol (ET) and stress on β‐endorphin and catecholamine (CA) levels, male rats pretreated with ET (3.0 g/kg, i.p.) or saline were immobilized for 30 min and killed 90 min after the initial injection. Stress resulted in (a) an increase in plasma levels of norepinephrine (NE, 243%), epinephrine (E, 175%), β‐endorphin (220%) and corticosterone (CS, 151%) and a decrease in dopamine (DA, 54%); (b) a decrease in hypothalamic NE (15%) and β‐endorphin (33%) levels and an increase E (23%) and DA (58%) levels; (c) a decrease in pituitary β‐endorphin levels in both the neurointermediate (23%) and anterior (131%) lobes. Treatment with ET resulted in: (a) an increase in plasma NE (81%), E (53%), CS (71%), and β‐endorphin (33%) levels and decrease in DA (54%); (b) a decrease in the hypothalamic NE (12%) levels and an increase DA (27%) and β‐endorphin (46%) levels, and (c) a decrease in β‐endorphin (15.5%) in the intermediate lobe of the pituitary. Treatment with ET of stressed animals had only a small effect: (a) in plasma NE, E, CS, and β‐endorphin levels decreased by 30, 31, 14, and 36%, respectively; (b) in the hypothalamus DA levels decreased by 40% and β‐endorphin increased by 71%; (c) in the pituitary β‐endorphin increased in both the intermediate lobe (25%) and anterior (50%) lobes. Thus when the data of the stressed ET‐treated group is compared to that of the nonstressed saline injected group, none of the measures differ significantly. These results confirm our earlier work indicating a significant interaction of ET and stress.
Effects of Ethanol on Arachidonic Acid Incorporation Into Lipids of a Plasma Membrane Fraction Isolated from Brain Cerebral Cortex
Authors: Lin Teng‐Nan , Sun Albert Y. , Sun Grace Y.
Published: April 2006

In the presence of ATP, MgCl2, and CoASH, somal plasma membranes isolated from rat cerebral cortex were active in transferring arachidonic acid to phosphatidylinositols, phosphatidylcholines, and triacylglycerols. Ethanol (350–525 mM) added to the incubation mixture inhibited arachidonic acid incorporation into phospholipids, while it enhanced the incorporation into triacylglycerols. Under these conditions, ethanol was found to react with arachidonic acid to form arachidonoyl ethyl ester. The incorporation of labeled arachidonic acid into glycerolipids as well as the synthesis of ethyl esters required the presence of ATP and CoASH for maximal activity. Nevertheless, each uptake process exhibited a unique pH profile. The esterification of arachidonic acid was not specific for ethanol as other aliphatic alcohols (e.g., propanol and butanol) were also able to react with labeled arachidonic acid to form the respective esters. Somal plasma membranes isolated from mice after chronic ethanol administration showed an increase in arachidonoyl transfer to both phospholipids and triacylglycerols. When these membranes were challenged with ethanol (325 mM), those isolated from the chronic ethanol group showed a greater increase in the labeling of triacylglycerols and ethyl esters than those from controls. Thus, different acyltransferases exhibite different responses to the effects of ethanol in vitro and in vivo.
Toxicology Screening in Acute Spinal Cord Injury
Authors: Heinemann Alien W. , Schnoll Sidney , Brandt Michael , Maltz Roger , Keen Mary
Published: April 2006

The validity of self‐reported intoxication at time of spinal cord injury (SCI) was examined for 88 cases at admission to an acute SCI center by comparing self‐reports with serum and urine analyses. Serum ethanol greater than 50 mg/dl was the most frequently found substance (observed in 40% of the cases) followed by urine analysis evidence of cocaine (14%), cannabinoids (8%), benzodiazipines (5%), and opiates (4%). Evidence of substances with abuse potential was found in urine for 35% of the sample. While 62% of the sample had either serum ethanol greater than 50 mg/dl or a positive urine analysis, only 42% of the sample reported being under the influence of some substance at the time of SCI. Although the relationship between these two measures was statistically significant, self‐report and toxicology analyses were discordant in 34% of the cases. These results suggest that routine drug testing at admission to an SCI center will produce both false‐negative and false‐positive results if substance presence alone is interpreted as evidence of intoxication.
Evidence of Increased Class I MHC Expression on Human Peripheral Blood Lymphocytes during Acute Ethanol Intoxication
Authors: Kolber Michael A. , Walls Ron M. , Hinners Marion L. , Singer Dinah S.
Published: April 2006

Certain ethanol‐related diseases in humans have been linked to disorders of immunity. Although humoral and cellular immunity have been studied, the precise mechanisms whereby ethanol use leads to tissue damage remain unknown. In order to explore the hypothesis that ethanol may lead to alteration in expression of tissue Class I major histocompatibility antigen causing an autoimmune phenomenon, a population of acutely ethanol‐intoxicated patients was studied. Measurement of Class I major histocompatibility antigen on peripheral blood lymphocytes in this population showed a highly significant (p < 0.01) increase over controls. The role that this increased antigenicity may play in the evolution of clinical disease is discussed.
Early Measures of Maternal Alcohol Misuse as Predictors of Adverse Pregnancy Outcomes
Authors: Russell Marcia , Skinner Jeremy B.
Published: April 2006

Pregnancy outcome was studied in 531 obstetric outpatients with respect to maternal alcohol consumption prior to pregnancy recognition, (absolute alcohol per day prior to pregnancy, PPAA) and indications of problem drinking (IPD). Multiple regression was used to predict pregnancy outcome with PPAA and IPD, controlling for potentially confounding sociodemographic and health factors.

PPAA predicted spontaneous abortion and lowered Apgar scores. The risk of spontaneous abortion increased an average of 25% for each additional ounce of absolute alcohol consumed per day (p < 0.05). Adverse pregnancy outcomes related to intrauterine growth were more strongly related to IPD than PPAA, and IPD remained a significant predictor even after controlling for PPAA. The strongest association was with head circumference (p < 0.01); logistic regression indicated that for each additional indication of problem drinking reported, risk of head circumference below the 10th percentile increased 2.77 times. Other pregnancy outcome measures negatively related to IPD were 5‐min Apgar scores (p < 0.05), birth weight (p < 0.10), and 1‐min Apgar scores (p < 0.10). No significant curvilinear alcohol effects or interactions were observed.

These findings highlight the potential clinical utility of PPAA and IPD in the early identification of women whose alcohol use puts their pregnancies at high risk.
Ethanol Withdrawal Increases Sensory Responsiveness of Single Somatosensory Cortical Neurons in the Awake, Behaving Rat
Authors: Chapin John K. , Woodward Donald J.
Published: April 2006

This study investigated the effects of ethanol withdrawal on sensory responses of single neurons recorded in the somatosensory (SI) cortex of awake, behaving, ethanol‐dependent rats. Eleven rats were fed an ethanol‐containing liquid diet for 90‐120 days, while 11 weight‐matched controls were pair‐fed an equivalent sucrose containing diet to equalize caloric intake. Single SI cortical neurons in the chronically treated rats were recorded continuously over several hours after withdrawal from ethanol, and after reintoxication induced by intraperitoneal injection of 10% (v/v) ethanol solution. Intoxication and withdrawal related changes in sensory responsiveness of these neurons were quantitatively measured by stimulating through electrodes chronically implanted under the skin of the forepaw. Sensory response histograms constructed from these stimuli showed a characteristic pattern, typically consisting of two early excitatory peaks (Ela and Elb), followed by an inhibition (11), and in some neurons, a late excitatory response (E2). As withdrawal advanced, the sensory response histograms exhibited marked increases in the magnitudes of the Ela, 11, and E2 responses, coupled with a reduced spontaneous discharge rate. These changes are similar to, but quantitatively greater than, those which have previously been observed in normal and control rats during “immobile arousal” behaviors, which can be evoked when an experimenter holds the animals still, producing an immobile “aversive arousal.” In withdrawing animals this same “holding” manipulation tended to markedly exacerbate and accelerate behavioral and neurophysiological signs of withdrawal. By contrast, the same manipulations had little effect when carried out during light intoxication or early stages of withdrawal. Thus, the physiological effects produced during withdrawal were similar to, and synergited with those normally associated with aversive arousal, producing effects far in excess of those seen in normal animals.
Beef Fat Prevents Alcoholic Liver Disease in the Rat
Authors: Nanji Amin A. , Mendenhall Charles L. , French Samuel W.
Published: April 2006

The amount and type of dietary fat is thought to be important in the pathogenesis of alcoholic liver disease (ALD). We investigated the role of different dietary fats in our rat model for ALD. Liver pathology was evaluated in rats fed ethanol and lard or tallow or corn oil over a period of 2 to 6 months. All experimental animals were pair‐fed the same diet as controls except that glucose was isocalorically replaced by ethanol. Rats fed tallow and ethanol developed none of the features of ALD, those fed lard and ethanol developed minimal to moderate disease, rats fed corn oil and ethanol developed the most severe pathology. The degree of histopathological abnormality correlated with the linoleic acid content of fat in the diet (tallow 0.7%, lard 2.5%, corn oil 56.6%). We postulate that linoleic acid facilitates development of ALD and provides an explanation for our previous epidemiological observations.
Effect of Acute Ethanol Intake and Hangover on the Levels of Plasma and Urinary Catecholamines and Lymphocytic β‐Adrenergic Receptors
Authors: Heikkonen Erkki , Mäki Tiina , Kontula Kimmo , Ylikahri Reino , Härkönen Matti
Published: April 2006

To determine whether acute ethanol administration affects the function of the adrenergic system the concentrations of plasma catecholamines and cyclic AMP (CAMP), the level of lymphocytic β‐receptors, the concentration of basal and isoproterenol‐stimulated lymphocytic cAMP and the excretion of urinary catecholamine metabolites were studied in six healthy men. These parameters were also measured during the hangover, both under resting condition and during an anaerobic ergometer exercise. Acute intake of ethanol (1.5 g/kg body weight) had no statistically significant effect either on plasma adrenaline and noradrenaline concentrations or β‐adrenergic receptor levels. Ethanol consumption did neither change the urinary excretion of catecholamine metabolites (homovanillic acid, normetanephrine, metanephrine, and 3‐methoxyhydroxymandelic acid). Exercise was associated with a 6‐10‐fold elevation in plasma adrenaline and noradrenaline concentrations and with a two‐ to threefold elevation on β‐adrenergic receptor levels. This effect of exercise was not modified by preceding alcohol intake and resulting hangover. These preliminary findings suggest that acute alcohol intake does not significantly alter the concentration and functioning of human β‐adrenergic receptors.
Exposure of Rats to Ethanol from Postnatal Days 4 to 8: Alterations of Cholinergic Neurochemistry in the Cerebral Cortex and Corpus Striatum at Day 20
Authors: Light Kim E. , Serbus Dellan C. , Santiago Melissa
Published: April 2006

Male and female rat pups were administered ethanol (3 g/kg/dose) twice daily by intragastric intubation between postnatal Day (PN) 4 and 8. Pups were maternally reared throughout the exposure period and until sacrifice on PN20. The consequences of this growth spurt exposure to ethanol were measured by an impact upon body growth, as well as upon specific growth parameters and cholinergic neurochemical factors within the cerebral cortex and corpus striatum. Specific endpoints included muscarinic receptor binding dynamics, acetylcholinesterase (AChE) and choline acetyltransferase (CAT) activities, regional wet weights, and subcellular protein content. In male pups, ethanol resulted in a significant enhancement of body weight gain and an increase in striatal but not cortical mass. Additionally, ethanol exposure resulted in a significant increase in striatal muscarinic receptor affinity, regardless of gender. This was accompanied by evidence of a significantly greater density of striatal muscarinic receptors in males versus females, regardless of treatment. Overall, the ethanol‐associated effects are suggestive of a drug‐induced developmental delay. Gender‐specific, treatment‐independent differences were also detected in the developing brain regions. Thus, regardless of treatment, cerebral cortical S1‐level protein content was found to be significantly greater in males than in females. Furthermore, there were gender‐based, significant differences in AChE activity within the striatum of control pups (males > females). Ethanol exposure resulted in a loss of this gender‐based difference. We conclude that the cholinergic neurochemical development occurring in the striatum of the female rat brain between PN4 and 8 is exquisitely sensitive to ethanol‐induced developmental delays which are not remediable by 12 subsequent days of maternal rearing in the absence of ethanol exposure.
Placebo Responding in the Same Direction as Alcohol in Women
Authors: Newlin David B.
Published: April 2006

Pavlovian conditioning studies with alcohol in humans have been performed exclusively with men subjects. Men demonstrate a placebo response opposite in direction to alcohol, which Newlin (Alcohol Clin Exp Res 9411‐416, 1985) termed an antagonistic placebo response. The current study used normal women subjects given alcohol, placebo, or a soft drink control. Placebo significantly (p < 0.05) increased heart rate compared to the control condition, and this placebo response was in the same direction as the effect of alcohol. The correlation of heart rate change with reported intoxication was +0.44 in women, when it was negative in men (Newlin DB Alcohol Clin Exp Rer 9:411‐416, 1985). These results, when considered in relation to other data concerning individual differences in antagonistic placebo responding, suggest a pattern in which risk for alcoholism is negatively related to placebo responding.
Comparison of Effects of Long‐Term Ethanol Consumption on the Heart and Liver of the Rat
Authors: Cunningham Carol C. , Kouri David L. , Beeker Kelly R. , Spach Priscilla I.
Published: April 2006

Alterations in heart and liver metabolism were determined periodically in Sprague‐Dawley rats pair‐fed a liquid diet (ethanol, 36% of calories) for times as long as 1 year. In liver mitochondria the rate of ATP synthesis was lowered significantly after ethanol administration for 1 month and longer feeding periods. In liver microsomes from ethanol‐fed animals, ethanol oxidation and aniline hydroxylation increased 1.5‐ and 3.5‐fold, respectively, after 1 month and remained elevated at the longer feeding intervals. Electron microscopic analyses of heart left ventricles revealed no alterations from ethanol consumption for 1 month. Alterations including disrupted mitochondrial cristae, dilatation of sarcoplasmic reticulum, and widening of the intercalated discs were observed after 6.5‐month feeding periods. Myocardial concentrations of creatine, creatine phosphate, ATP, ADP, and Pi remained constant even after ethanol consumption for 9 months. After a 12‐month feeding period slight changes in cardiac mitochondrial energy‐linked properties were observed which were not as pronounced as those occurring in liver mitochondria. The activity and oligomycin sensitivity of the ATPase were not altered in cardiac mitochondria, whereas in liver preparations significant alterations in these properties of the ATPase were apparent after ethanol consumption for 1 month and the longer feeding periods. These observations suggest that the liver responds more quickly and dramatically to chronic ethanol consumption than does the heart.
Prenatal Ethanol Exposure Alters Adrenocortical Development of Offspring
Authors: Weinberg Joanne
Published: April 2006

Interactive effects of prenatal ethanol and maternal nutritional status on reproductive outcome and maternal and offspring adrenocortical activity were examined. Ethanol was administered to pregnant females in liquid diets (36% ethanol‐derived calories) which were marginal or optimal in terms of requirements for pregnancy. Both pair‐fed and ad libitum fed control groups were included. Females consuming ethanol from gestation Day 1 through parturition gained less weight, were delayed in parturition, and had fewer and smaller live born young than pair‐fed or control females, regardless of whether they consumed marginal or optimal diets. Withdrawing ethanol on Day 21 of gestation attenuated many of ethanol's adverse effects on reproductive outcome. However, prenatal maternal ethanol intake altered adrenocortical activity/responsiveness of the mother, the fetus, and the preweaning offspring, regardless of maternal nutritional status. Relative adrenal weights and basal corticos‐terone levels were increased in the dam both prenatally and at parturition. Ethanol‐exposed fetuses (A) had increased relative adrenal weights but lower basal corticosterone levels than pair‐fed (PF) and control (C) fetuses on gestation Day 21. At birth, plasma and adrenal corticosterone levels were increased, while absolute adrenal weights and corticosterone binding globulin (CBG) binding capacity were decreased in A neonates. At 5 days of age, A pups showed reduced plasma corticoid responses to ether at 15 min poststress and to novelty or saline injection at 90‐min post stress compared to PF and C pups. CBG binding capacity was also reduced in A pups. At 10 days of age, plasma corticosterone levels were lower overall in A and PF than in C pups following exposure to a number of different acute stressors while at 18 days plasma corticoids were decreased and adrenal corticosterone was increased in A compared to PF and/or C pups. These data support and extend previous studies indicating that in utero ethanol exposure alters postnatal adrenocortical development. This effect is specific to ethanol and unaltered by maternal nutritional status.
Chemiluminescence from Acetaldehyde Oxidation by Xanthine Oxidase Involves Generation of and Interactions with Hydroxyl Radicals
Authors: Puntarulo Susana , Cederbaum Arthur I.
Published: April 2006

The ability of acetaldehyde to generate free radicals is often ascribed to its oxidation by xanthine oxidase, with the subsequent production of reactive oxygen intermediates. Chemiluminescence associated with the oxidation of acetaldehyde by xanthine oxidase was inhibited by superoxide dismutase, catalase, or several hydroxyl radical scavenging agents, and was stimulated by the addition of EDTA or ferric‐EDTA. This suggests that the light emission is primarily due to the production of hydroxyl radicals via an iron‐catalyzed Haber‐Weiss type of reaction. Chemiluminescence with hypoxanthine as substrate for xanthine oxidase was much lower than that found with acetaldehyde, yet rates of hydroxyl radical production were greater with hypoxanthine. Acetaldehyde increased light emission in the presence of hypoxanthine by a greater than additive effect. These results suggest a complex role for acetaldehyde in catalyzing xanthine oxidase‐dependent chemiluminscence. It appears that besides being a substrate for xanthine oxidase, acetaldehyde also reacts with the generated hydroxyl radical to produce acetaldehyde radicals, which yield chemiluminescence upon their decay. Further studies will be required to evaluate whether the production of such species contributes to or plays a role in the generation of reactive oxygen intermediates and toxicity associated with acetaldehyde metabolism.
Effects of 3‐Arnino‐1,2,4‐triazole on Ethanol‐induced Open‐Field Activity: Evidence for Brain Catalase Mediation of Ethanol's Effects
Authors: Aragon C. M. G. , Spivak K. , Amit Z.
Published: April 2006

The role of brain catalase in the mediation of ethanol's effects on motor activity was investigated. Male Long‐Evans rats were pretreated with i.p. injections of the catalase inhibitor, 3‐amino‐1,2,4‐triarole (AT) (1 g/kg) or saline (S). Four hours later, animals in each group received i.p. injections of one of two doses of ethanol (ETOH) [1.0 g/kg (E1) or 2.0 g/kg (E2)] or one of two volumes of distilled water (W1 or W2). Ten minutes alter the administration of these agents, animals were placed in open‐field chambers and motor activity was recorded during a 10‐min testing period. Results indicated that the motor depression produced by 2.0 g/kg of ETOH was significantly attenuated in AT pretreated rats (group AT‐E2). AT pretreatment, however, had no effect on motor activii for subjects injected with 1.0 g/kg ethanol or water. Total brain catalase activity in AT‐pretreated animals was 15% of control animals. No differences in blood ethanol levels were obsewed between AT‐ and S‐pretreated animals. An interaction between ethanol and AT at the level of the central nervous system is suggested. The results of the present study suggest that brain catalase activity may be involved in ethanol's effects. They also provide further support for the notion that acetaldehyde may be produced directly in the brain via catalase and that it may be a factor mediating some of ethanol's central effects.
Alcohol and Breast Cancer: An Overview
Authors: Lowenfels Albert B. , Zevola Susan A.
Published: April 2006

We have reviewed available reports from 1974‐1987 linking alcohol consumption with breast cancer. Although three prospective studies show a slightly increased risk of breast cancer for consumers versus nonconsumers of alcohol, the results of correlation studies and case control studies have been inconsistent. In both positive and negative studies the amount of alcohol consumed by women with breast cancer was low, and if there is an association between alcohol and breast cancer, then it would appear that complete abstinence would be required to reduce the risk of this disease. At present, it seems premature to consider such a drastic recommendation until further information becomes available.
Effect of Ethanol on Human Placental Transport of Model Amino Acids and Glucose
Authors: Schenker Steven , Dicke Jeffrey M. , Johnson Raymond F. , Hays Susan E. , Henderson George I.
Published: April 2006

Prior studies in rodents, sheep, and subhuman primates have shown that ethanol, especially atter chronic exposure, inhibits the transport of amino acids by the placenta. A small decrease in glucose transport by rat placenta chronically exposed to ethanol has also been noted. With human placental slices, however, only pharmacological (high) concentrations of ethanol impaired uptake of amino acids, and there are no data on glucose transport. In the present study, the effect of brief exposure to ethanol on human placental transport of model amino acids and glucose was studied by two techniques not previously jointly employed for this—the perfused human placental cotyledon and human placental vesicle systems. The nonmetabolizable amino acids, α‐aminoisobutyric (AIB) acid and cycloleucine (CLEU), as well as d‐glucose, and nonmetabolized glucose (3‐O‐methyl‐d‐glucose), were used as probes. AIB and CLEU are transferred normally by active transport and d‐glucose by facilitated transport from maternal to fetal compartments. The pertused placental system was exposed to ethanol (300‐500 mg%) for 2–4 hr and the vesicles to 200–400 mg% ethanol for times varying from 10 min to 48 hr. There was no impairment of AIB, d‐glucose, or 3‐O‐methyl‐d‐glucose transfer by ethanol using these techniques. Normally, about 60% of AIB transport by human placenta is sodium dependent. This component (using the vesicle system) was also not impaired by ethanol. Ethanol caused a very small decrease of CLEU clearance by the perfused human placenta (p= 0.05) but not using vesicles. We conclude that transport of amino acids and glucose by the human placenta is relatively resistant to the inhibitory effects of brief ethanol.
Influence of Improved Drinking Habits on Brain Atrophy and Cognitive Performance in Alcoholic Patients: A 5‐Year Follow‐up Study
Authors: Muuronen Antti , Bergman Hans , Hindmarsh Tomas , Telakivi Tiina
Published: April 2006

In the period 1977‐1979, a sample of consecutively admitted alcoholic in‐patients was studied with CT scan of the brain and neuro‐psychological tests. A subsample of 52 patients met the following criteria: age less than 46 years, no history of severe head injury or focal signs of traumatic brain damage, and no history of liver disease, drug abuse, or long‐lasting anticonvulsant therapy. However, 72% of the patients showed brain atrophy and 49% intellectual impairment as compared to 16% and 13%, respectively, in an age‐matched sample of men from the general population. Five years later, after excluding patients with head trauma, serious alcoholic liver disease and drug abuse, 37 patients were reinvestigated.

Sixteen patients were abstinent or had greatly improved drinking habits during the 5‐year follow‐up period and 21 were still drinking. Alcohol abstinence was found to be associated with a regress of cortical atrophy and central atrophy as assessed by the width of the 3rd ventricle. However, the recovery was not complete as compared with the prevalence of atrophy in the sample from the general population. Among the patients a significant improvement in one cognitive test and a trend to improvement in some other tests associated with improved drinking habits was observed. Regression of central atrophy as assessed by a decreased diameter of the 3rd ventricle was associated with improvement in the very same cognitive tests.

The results suggest that both atrophy of the brain and cognitive ability can improve in alcoholics who give up drinking. The CT‐findings indicate that changes of the tissues close to the 3rd ventricle is of clinical relevance in common types of alcoholism.
Elevation of Plasma Salsolinol Sulfate in Chronic Alcoholics as Compared to Nonalcoholics
Authors: Faraj Bahjat A. , Camp Vernon M. , Davis Donald C , Lenton John D. , Kutner Michael
Published: April 2006

This report describes a radioenzymatic assay for the measurement of salsolinol and dopamine sulfate levels in plasma. It is based on a sulfatase‐catalyzed hydrolysis of the sulfoconjugates followed by catechol‐O‐methyltransferase and [methyl‐3H]‐S‐adenosylmethion‐ine‐catalyzed O‐methylation of the resulting free salsolinol and dopamine. Rapid thin‐layer chromatographic separation of the formed labeled metabolites attributed to the specificity of the differential enzymatic assay of salsolinol and dopamine. This assay was used to study plasma salsolinol and dopamine levels in a group of adult males (n= 36) serving as controls and a group of hospitalized chronic alcoholics (n= 18). The results (mean and range) of this preliminary study show that alcoholics had significantly (p < 0.0001) elevated plasma concentration of salsolinol sulfate (497; 50–1331 pg/ml) as compared to controls (93; 0–232 pg/ml). This was accompanied by significant (p < 0.0003) elevation in plasma levels of dopamine sulfate. Elevation of plasma salsolinol sulfate reported here may be interpreted as a reflection of abnormalities in oxidative metabolism of dopamine, metabolically derived acetaldehyde, and/or biological carbonyls in chronic alcoholics.
Methanol as a Marker of Alcohol Abuse
Authors: Roine Risto P. , Eriksson C. J. Peter , Ylikahri Reino , Penttila Antti , Salaspuro Mikko
Published: April 2006

Serum methanol levels were studied in 16 skid‐row alcoholics, 16 alcoholics entering a detoxification unit, 193 drunken drivers, and 50 social drinkers, all of whom had a blood‐ethanol concentration exceeding 5 mmol/liter at the time of sampling. Highest mean serum methanol level was found in alcoholics entering detoxification (636 ± 68 μmol/liter, p < 0.001 as compared to social drinkers), followed by skid‐row alcoholics (567 ± 105 μmol/liter, p < 0.001), drunken drivers (231 ± 11 μmol/liter, p < 0.001) and social drinkers (127 ± 10 μmol/liter). During 2 days heavy drinking mean serum methanol concentration in 10 nonalcoholic volunteers increased from 177 ± 15 μmol/liter 1 h after the beginning of drinking to 322 ± 29 μmol/ liter 42 h after the beginning of drinking (p < 0.001). In 70 of the drunken drivers urinary methanol concentration was determined as well and a fairly good correlation (r =+0.56, p < 0.001) between serum and urinary methanol levels were found. Our results suggest that methanol determined either from serum or urine can be used as a biological marker of alcohol abuse.
Liver Transplantation for Alcoholic Liver Disease: A Consideration of Reasons For and Against
Authors: Van Thiel David H. , Gavaler Judith S. , Tarter Ralph E. , Dindzans Vincents J. , Gordon Robert D. , Iwatsuki Shunzaburo , Makowka Leonard , Todo Satoru , Tzakis Andreas , Starzl Thomas E.
Published: April 2006

Orthotopic liver transplantation is a clinical procedure that has been accepted widely as the treatment of choice for individuals with advanced chronic liver disease. As such, its application to the important clinical problem of alcoholic liver disease is inevitable. The arguments for and against liver transplantation for individuals with advanced alcoholic liver disease are presented.
LS X SS Recombinant Inbred Strains of Mice: Initial. Characterization
Authors: DeFries J. C. , Wilson James R. , Erwin V. Gene , Petersen D. R.
Published: April 2006

In order to assess the genetic correlates of differences in ethanol‐induced anesthesia, a set of 27 recombinant inbred (RI) strains was derived from an initial cross of the “long‐sleep” (LS) and “short‐sleep” (SS) selected lines of mice. In generations F24 and F25, samples of 534 and 580 mice from the LSXSS RI strains were tested for fall time, sleep time, and blood ethanol at awakening subsequent to intraperitoneal injection of a 4.1‐g/kg body weight dose of ethanol. Approximately 2 weeks later, mice from F24 were also tested for body temperature lowering and blood‐ethanol elimination rate (β60). Differences among the average ethanol‐induced sleep‐time scores of the RI strains are large (ranging from 36 to 171 min) and account for over 50% of the observed variance. Effects due to generation, sex, litters within strains, and the interaction between strain and generation are also significant, but account for relatively small proportions of the total variance. Quantitative genetic analyses of these data suggest that differences in sleep‐time scores are polygenic; however, allelic differences at the albino (c) locus may have a pleiotropic effect. Genetic correlations between sleep time and blood ethanol at awakening (‐0.79) and between body temperature 60 min after injection and β60 (+0.48) are significant. Because differences among the LSXSS RI strains are large and highly reliable, they should be valuable animal models for testing more searching hypotheses about the etiology of individual differences in ethanol‐induced anesthesia.
Cell‐mediated Immune Responses Associated with Short Term Alcohol Intake: Time Course and Dose Dependency
Authors: Dehne Nancy E. , Mendenhall Charles L. , Roselle Gary A. , Grossman Charles J.
Published: April 2006

Using a rat model, we repolt here the duration of heavy drinking necessary to produce immunosuppression, the recovery time after such alcohol‐induced immunosuppression, and the variations in immune response associated with varied amounts of alcohol consumption. Immune status was evaluated by means of delayed cutaneous hypersensitivity (DCH)‐like responses to phytohemagglutinin. The daily consumption of 5 g of ethanol/kg body weight/d resulted in a prompt reduction in DCH‐like responses which was significant by Day 3 (p = 0.03) and maximal by Day 11 (45% of baseline). These data were consistent with a similar reduction of migration inhibitory factor activity in spleen cells from ethanol fed rats. Cessation of ethanol resulted in a return to baseline within 4 days. In a second experiment ethanol was administered daily in doses ranging from 0.5 to 6.0 g/kg. Early (Day 5) low dose ethanol (0.5–2 g/kg) stimulated immune response (153–188% of baseline) while high dose (6.0 g/kg) suppressed (79% of baseline). Continued treatments resulted in a loss of stimulation at low dose and increased suppression at higher doses. The relationship of these animal studies to human binge drinking and the possible risk for infection in the alcoholic remains to be established.
Effect of Prenatal Ethanol Administration on the Urogenital System of Mice
Authors: Boggan William O. , Monroe Bob , Turner William R. , Upshur Jane , Middaugh Lawrence D.
Published: April 2006

The purpose of the present series of studies was to determine whether an obstruction in the urogenital system or vesicoureteral reflux (reflux, the retrograde passage of urine from the bladder into the kidney) existed in mice prenatally exposed to ethanol which might account for the high incidence of hydronephrosis and hydrour‐eier observed. In order to examine these possibilities, indigo carmine was injected into the bladder of 19‐day fetuses previously exposed to ethanol on Day 10 of gestation and the presence of hydronephrosis and/or reflux determined. As expected, we found a greatly increased incidence of hydronephrosis and hydroureter. In addition, there was a significant increase in reflux in the ethanol‐treated mice. The incidence of reflux appeared to be related to the severity of the hydronephrosis observed, though cases of hydronephrosis without reflux and reflux without hydronephrosis were found. These data suggest both hypotheses may be salient and that a multiplicity of urogenital abnormalities are found following prenatal ethanol exposure.
A Morphometric Study of the Effects of Ethanol Consumption on Lactating Mammary Glands of Rats
Authors: Steven William M. , Bulloch Brian , Seelig Leonard L.
Published: April 2006

Morphometric procedures were used to quantitate changes induced by ethanol in tissue components of rat mammary gland. Rats were pair‐fed ethanol‐containing or isocaloric control liquid diets formulated for pregnant or lactating animals, or maintained on regular laboratory chow. Short term animals were pair‐fed ethanol or control diets from Day 1 of pregnancy through lactation Days 2 or 10. Long term animals were pair‐fed ethanol or control diets for 25 days prior to mating, and then through pregnancy to lactation Days 2 or 10. Point counting was used to determine the volume fractions (vf) of alveolar epithelium, lumen, and connective tissue in the mammary glands. In chow‐fed animals the percentage of alveolar epithelium remained constant from late pregnancy through lactation, while the amount of connective tissue decreased and that of alveolar lumen increased. This indicates the sensitivity of this procedure to detect changes in tissue volume fractions during mammary proliferation. No changes from the normal controls were found in any tissue component in short term ethanol or pair‐fed animals. At lactation Day 2, long term ethanol‐treated animals demonstrated a significant decrease in the percentage of alveolar epithelium and a significant increase in the percentage of total connective tissue as compared to pair‐fed and chow‐fed control animals. However, by Day 10 of lactation, no changes were found in any of the tissue components in long‐term ethanol‐fed versus control animals. These results indicate that ethanol consumption can alter mammary gland structure during the early stages of lactation, even when adequate levels of dietary protein are maintained.