bluuebunny/crossref_metadata_2025 huggingface dataset:
Progesterone and Prostaglandin H Synthase‐2 Involvement in Alcohol‐Induced Preterm Birth in Mice
Authors: Cook Jocelynn L. , Zaragoza Dean B. , White Nancy M. , Randall Carrie L. , Olson David M.
Published: May 2006

Background

: Recently, an association between alcohol consumption during pregnancy and shortened gestational length has been reported, but the underlying mechanisms remain unknown. Progesterone (P4) and prostaglandins have been shown to play important roles in parturition in both human and animal models. Recently, it has been suggested that prostaglandin H synthase‐2 (PGHS‐2) is responsible for prostaglandin changes associated with term and preterm labor. It is possible that alcohol induces preterm birth by altering P4 or PGHS‐2 levels. These studies were designed to determine the role of P4 and PGHS‐2 in alcohol‐induced preterm labor in mice.

Methods

: Experiment 1: Pregnant dams treated with either vehicle or alcohol (6 g/kg, intragastrically) on gestational day (GD) 16 were killed at various times in gestation up to the time of delivery. Plasma P4 levels were measured by radioimmunoassay and uterine PGHS‐2 mRNA expression was measured by Ribonuclease Protection Assay. Results indicated that alcohol treatment was associated with an earlier decline in plasma P4 levels and an earlier rise in uterine PGHS‐2 mRNA levels during gestation. Experiment 2: Pregnant C57BW6J females were treated with either P4 (2.0 mg, subcutaneously) or vehicle (sesame oil) 2 hr before receiving either 6 g/kg alcohol (intragastrically) or vehicle (isocaloric sucrose) on gestational day (GD) 16. Results indicate that P, pretreatment effectively antagonized alcohol‐induced preterm delivery. Experiment 3: On GD16, pregnant dams received either 100 mgkg nimesulide (a specific PGHS‐2 inhibitor) or vehiclc (saline) subcutaneously, 2 hr before treatment with either 6 g/kg alcohol (given intragastrically) or isocaloric sucrose. Nimesulide was effective in antagonizing alcohol‐induced preterm labor.

Conclusions

: Together, these data suggest that both P4 and PGHS‐2 may play roles in alcohol‐induced preterm birth.
Application of the Capture‐Recapture Method to Epidemiological Studies of Alcohol Related Problems
Authors: Shenassa Edmond D.
Published: May 2006

The capture‐recapture method is used to enumerate members of populations for which a complete census is not possible. The use of this method to enumerate individuals with alcohol‐related problems requires special considerations. This article comments on these considerations and addresses the strengths and weaknesses of this method for enumerating individuals with alcohol‐related problems in a community.
The Effects of Season and Alcohol Intake on Mineral Metabolism in Men
Authors: Perry Horace M. , Horowitz Michael , Fleming Shantiel , Kaiser Fran E. , Patrick Ping , Morley John E. , Cushman William , Bingham Stephen , Perry H. M.
Published: May 2006

We have examined the relationship between self‐reported alcohol intake (SRAI), season and mineral metabolism in a series of 96 men aged 32 to 78 years of age. Alcohol intake was reported as between 0 and 50 oz/week. SRAI correlated positively with liver function tests, including serum bilirubin, alkaline phosphatase, and AST initially and at 6 months. In addition, SRAI correlated with serum calcium, testosterone, estradiol, and immunoreactive parathyroid hormone (iPTH) as well as urinary calcium [per 100 mg of creatinine (Cr)], and pyridinoline crosslinks (DPC) (per 100 mg of Cr). We have divided the participants into two groups on the basis of their reported alcohol intake. Individuals with none‐to‐moderate intake had <8.4 oz/week of ethanol. Those with moderate or heavier intake had 8.4 oz or more of ethanol/week. Individuals with none‐to‐moderate SRAI had a significant seasonal increase in iPTH, osteocalcin, urine DPC/100 mg of Cr and a decrease in distal forearm bone mineral density, 25 hydroxy‐vitamin D (250HD), and urinary calcium/100 mg of Cr. Individuals with moderate or heavier SRAI only had significant seasonal decrease in 250HD. We have concluded that alcohol intake decreases seasonal change in serum iPTH. The biological effects of such alterations in parathyroid hormone levels include decreased seasonal loss of bone mineral density.
Cognitive Functioning Moderates the Relation Between Hyperactivity and Drinking Habits
Authors: Span Sherry A. , Earleywine Mitchell
Published: May 2006

Previous research reveals an inconsistent link between hyperactivity and drinking (Weiss and Hechtman, 1993). This study sought to investigate whether cognitive functioning moderates the relation between these two variables. One hundred participants completed three measures of drinking habits, two measures of hyperactivity, and four measures of cognitive functioning. Confirmatory factor analysis showed that a three‐factor model of hyperactivity, cognitive functioning, and drinking habits provided an excellent fit to the data. Stacked two‐group analyses revealed that cognitive functioning moderated the association between hyperactivity and drinking habits. Drinking habits and hyperactivity correlated 0.408 (p < 0.05) for individuals low on cognitive performance; the correlation between these constructs was only 0.120 (NS) for individuals high on cognitive performance. Higher levels of cognitive functioning may buffer individuals from drinking alcohol in accordance with their hyperactive symptoms.
Reduced EEG Alpha Power in the Male and Female Offspring of Alcoholics
Authors: Finn Peter R. , Justus Alicia
Published: May 2006

Abnormalities in resting EEG may be associated with a predisposition to alcoholism. Research also suggests that high levels of negative affect are important mediators of the predisposition to alcoholism in the offspring of alcoholics. This study tested the hypothesis that the offspring of alcoholics show deficits in EEG alpha and excessive EEG beta activity, which, in turn, would be associated with high levels of negative affect. Participants were 37 men and 27 women with a positive family history of alcoholism and 37 men and 29 women with a negative family history of alcoholism. Personal and family history of psychopathology, psychological traits, and resting EEG were each assessed in separate testing sessions. Results indicated that subjects with a family history of alcoholism had reduced relative and absolute alpha power in occipital (01, 02) and frontal (F3, F4, Fz) regions, and increased relative beta in both regions compared with subjects with a negative family history of alcoholism. EEG alpha and beta activity were not significantly correlated with trait anxiety, a diagnosis of depression, or antisocial traits. The results suggest that deficits in resting EEG alpha are associated with risk for alcoholism, although their etiological significance is unclear.
Alcohol Consumption in Rhesus Monkeys Depletes Tissues of Polyunsaturated Fatty Acids and Alters Essential Fatty Acid Metabolism
Authors: Pawlosky Robert J. , Salem Norman
Published: May 2006

Rhesus monkeys that were maintained on an adequate diet but with low levels of essential fatty acids (1.4 en% linoleic, 18:2n‐6, and 0.08 en%, linolenic acid, 18:3n‐3) became depleted of 20:4n‐6, and 22:6n‐3 in their livers, plasma lipoproteins, and erythrocytes during an 18‐month period of alcohol exposure (2.6 g kg‐1 day‐1). Monkeys that consumed alcohol also had higher plasma concentrations of 4‐hydroxynonenal compared to controls. The metabolism of 18:2n‐6 and 18:3n‐3 were evaluated in both groups of animals using deuterium‐labeled substrates over a 9‐day period. Alcohol consumption did not appear to have an effect on the absorption of either 2H5‐18:2n‐6 or 2H5‐18:3n‐3 ethyl esters into the circulation after a single oral dose. However, there was a greater enrichment of deuterium in the biosynthesized fatty acids, 20:4n‐6 and 22:6n‐3, in the plasma of the monkeys exposed to alcohol compared to controls. These results suggest that chronic alcohol exposure may lead to a stimulation of the rate at which long‐chain polyunsaturated fatty acids are biosynthesized to compensate for an increase in lipid peroxidation.
Effects of Chronic Ethanol Ingestion on the Vasoactive Intestinal Peptide Receptor‐Effector System From Rat Seminal Vesicle Membranes
Authors: Juarranz Maria G. , Marinero Maria J. , Bodega Guillermo , Prieto Juan C. , Guijarro Luis G.
Published: May 2006

We studied the modifications of the vasoactive intestinal peptide (VIP) receptor/effector system from the rat seminal vesicle after chronic ethanol ingestion. Ethanol treatment resulted in a decreased height of the secretory epithelium of seminal vesicle as well as in a weight loss of this gland. These morphological changes were accompanied by an increase of immunoreactive vasoactive intestinal peptide (VIP) levels and a decrease of the stimulatory effect of VIP adenylate cyclase activity in the seminal vesicle. The loss of sensitivity of the enzyme to VIP was conceivably related to a decrease in the affinity of VIP receptors rather than to a decrease in their number. The changes in the affinity of the VIP receptors were accompanied with a lower sensitivity of VIP binding to GTP, which suggest an uncoupling between the receptor and the transductor molecules. However, chronic exposure to ethanol did not modify either the levels of G‐protein subunits (αs and αi1/2) or the GTPase activity from seminal vesicle membranes. Moreover, ethanol feeding did not affect adenylate cyclase activity stimulated by forskolin or by Gpp(NH)p. Thus, ethanol‐induced changes in the sensitivity of adenylate cyclase to VIP appear to be attributed to an alteration in the VIP‐receptor/G‐protein interphase rather than in the G‐protein/adenylate cyclase connection.
A Follow‐Up Study on Chromosomal Aberrations in Lymphocytes of Alcoholics During Early, Medium, and Long‐Term Abstinence
Authors: Hüttner E. , Matthies U. , Nikolova T. , Ehrenreich H.
Published: May 2006

The frequencies of structural chromosomal aberrations were analyzed in peripheral blood lymphocytes of 31 chronic alcoholics at the beginning of an intensive outpatient treatment program at a neuro‐psychiatric clinic and were compared with 31 controls matched for gender, age, smoking habits, and nondrinkers. A statistically significant difference was observed in the level of chromosomal aberrations in somatic cells from alcoholics when compared with controls (3.01 % vs. 1.28%, p < 0.001). A follow‐up study was carried out for a subset of the patients after 3 months (8 subjects) and 12 months (14 subjects) of controlled abstinence. A statistically significant increase in the mean frequency of cells with aberrations was observed in the group of 14 subjects reinvestigated after 12 months of abstinence when compared with the mean value of the first blood samples immediately after hospitalization (4.61% vs. 3.01%; p < 0.001). An excessive increase in cigarette consumption during alcohol abstinence, reflected by a dramatic elevation of CO‐hemoglobin levels, may, at least in part, account for this finding. In conclusion, chronic alcoholism leads to genotoxic effects that, instead of recovering after 1 year of alcohol abstinence, are even enhanced, most likely due to the “shift in addictive behavior.”
Effects of Alcohol on Immediate‐Early Gene Expression in Primary Cultures of Rat Cortical Astrocytes
Authors: Yagle Kevin , Costa Lucio G.
Published: May 2006

Ethanol is a potent inhibitor of muscarinic receptor‐mediated proliferation in glial cells. Glial proliferation has been suggested as a major target of ethanol neurotoxicity during development, leading to the microencephaly that is a predominant feature of fetal alcohol syndrome. As part of an attempt to understand the mechanism of ethanol's inhibitory effects on muscarinic receptor‐mediated proliferation, this study investigated the effects of ethanol on the expression of the immediate‐early genes (IEGs), c‐fos and c‐myc, whose induction is thought to be an essential first step in the initiation of the mitogenic program. Unexpectedly, ethanol had no inhibitory effect on c‐fos and c‐myc mRNA expression induced in primary rat cortical astrocytes by the mitogens carbachol, histamine, or tetradecanoyl phorbol 13‐acetate; rather, a modest potentiation of IEG expression was observed in the presence of 25 to 100 mM ethanol. Control experiments showed that ethanol alone was capable of IEG mRNA induction, with 100 mM ethanol inducing IEG mRNA levels comparable with those induced by 100 ng/ml of tetradecanoyl phorbol 13‐acetate; as measured by [3H]thymidine incorporation, however, 25 to 100 mM ethanol had no effect on proliferation. Experiments with the protein kinase C inhibitor bisindolylmaleimide and the Ca2+ chelators BAPTA and EGTA indicated that this IEG induction by ethanol was not mediated by protein kinase C or Ca2+. A possible explanation for this ethanol‐induced IEG expression in the absence of a proliferative effect might be found in the increasing number of studies showing IEG involvement (especially that of c‐myc) in apoptosis.
Variable Dose Naltrexone‐Induced Hypothalamic‐Pituitary‐Adrenal Stimulation in Abstinent Alcoholics: A Preliminary Study
Authors: Farren Conor K. , O'Malley Stephanie , Grebski Gabriella , Maniar Swapnil , Porter Margaret , Kreek Mary Jeanne
Published: May 2006

Opiate antagonists have been found to stimulate the hypothalamic‐pituitary‐adrenal axis. However, despite established usefulness in the management of alcoholism, systematic, oral dose‐titrated naltrexone‐induced hypothalamic‐pituitary‐adrenal stimulation has never been studied in alcoholics. Six patients (5 males, 1 female) with DSM‐IV alcohol dependence, who were at least 4 weeks abstinent from any alcohol [mean 55 days (±SE 7.5)], were given four challenges of oral naltrexone (0, 25, 50, and 100 mg) in a randomized order at least 3 days apart, after an overnight fast. Naltrexone was administered at 9 AM; serum ACTH, cortisol, and prolactin were measured at time 0 and at 9 time points over the next 4 hr. Subjects also filled out a side effect questionnaire and an alcohol urge questionnaire. Physiological measurements of blood pressure and pulse rate were taken at the same time points. Repeated‐measures ANOVA of the changes in serum ACTHs over time revealed a significant effect of drug (placebo vs. any dose of naltrexone) (p < 0.05). Post‐hoc analysis revealed a significant difference between placebo and the 25 mg dose (p < 0.01), the 50 mg dose (p < 0.01), but no significance between the placebo and the 100 mg dose (p = 0.1). A repeated‐measures ANOVA of the changes in serum cortisols over time revealed a significant effect of drug (p < 0.01). Post‐hoc analysis revealed a significant difference between placebo and the 25 mg dose (p < 0.01), between placebo and the 50 mg dose (p < 0.05), and placebo and the 100 mg dose (p < 0.01). There was a significant between dose difference in pulse rate changes over baseline (p < 0.01), and post‐hoc analysis revealed a significant diminution in pulse rate at the 100 mg dose relative to placebo (p < 0.001), and to the other doses. There were no significant differences in reported side effects, alcohol urge questionnaire scores, or in other physiological measurements between doses. These data suggest a significant rise in ACTH and cortisol in response to naltrexone in alcoholics compared with placebo, with no differences between 25 mg, 50 mg, and 100 mg doses, and a significant diminution in pulse rate responses at the 100 mg dose.
A Comparative Evaluation of Substance Abuse Treatment: I. Treatment Orientation, Amount of Care, and 1‐Year Outcomes
Authors: Moos Rudolf H. , Finney John W. , Ouimette Paige Crosby , Suchinsky Richard T.
Published: May 2006

This article first explains the conceptual framework and plan of a naturalistic, multisite evaluation of Department of Veterans Affairs (VA) substance abuse treatment programs. It then examines the effectiveness of an index episode of inpatient treatment and the effectiveness of continuing outpatient care and participation in self‐help groups. The study was conducted among 3018 patients from 15 VA programs that emphasized 12‐Step, cognitive‐behavioral (CB), or eclectic treatment. Casemix‐adjusted 1‐year outcomes showed that patients in 12‐Step programs were the most likely to be abstinent, free of substance abuse problems, and employed at the 1‐year follow‐up. Patients who obtained more regular and more intensive outpatient mental health care, and those who participated more in 12‐Step self‐help groups, were more likely to be abstinent and free of substance use problems at the 1‐year follow‐up. These findings support the effectiveness of 12‐Step treatment and show that patients with substance use disorders who become more involved in outpatient care and self‐help groups tend to experience better short‐term substance use outcomes. Subsequent papers in this section focus on the proximal outcomes of treatment, patients with psychiatric as well as substance use disorders, patient‐treatment matching effects, and the link between program treatment orientation and patients’ involvement in and the influence of 12‐Step self‐help groups.
Ethanol Impairs Saccadic and Smooth Pursuit Eye Movements Without Producing Self‐Reports of Sedation
Authors: Holdstock Louis , de Wit Harriet
Published: May 2006

It has been suggested that eye movements provide a sensitive tool to assess the sedative‐like properties of drugs. However, the relationship between sedative‐like subjective effects and impairment in eye movements is not clear. For example, it is not clear whether drugs with stimulant‐like effects can also impair eye movements. This study evaluated whether ethanol, a drug with both sedative‐like and stimulant‐like properties, impairs eye movements, and whether the impairment observed after ethanol is related to its sedative properties. Twenty healthy men and women, aged 21 to 35, consumed beverages containing placebo or ethanol (0.4 or 0.8 g/kg) on three separate laboratory sessions, in randomized order. Eye movement and psychomotor and subjective responses were assessed before and at regular intervals for 3 hr after ingestion of the beverage. Subjects were divided post hoc into two groups, based on their sedative‐like or stimulant‐like subjective responses to ethanol. Nine subjects reported increases in sedative‐like effects after ethanol and 11 reported decreases in sedative‐like effects, and increases in stimulant‐like effects, after alcohol. Despite their distinctly different subjective responses to ethanol, the groups did not differ in the magnitude, time‐course or quality of responses on the eye movement measures. In both groups, ethanol decreased peak saccadic eye velocity and smooth pursuit gain. These results demonstrate the dissociation between impairment in eye movements and subjective feelings of sedation after ethanol, and show that eye movements can be impaired even when subjects are reporting stimulant‐like effects. The findings suggest that impaired eye movements are not a nonselective index of sedation, but may be related to specific drug actions on brain regions involved in generating these eye movements.
Differences in Neurophysiological Indices of Associative Learning in Alcohol‐Preferring and Nonpreferring Rats
Authors: Slawecki C. J. , Walpole T. , Somes C. , Li T.‐K. , Ehlers C. L.
Published: May 2006

Alcohol‐preferring (P) and ‐nonpreferring (NP) rats differ in baseline neurophysiological measures as well as in their neurophysiological responses to ethanol. In the present study, these lines of rats were assessed to determine whether they also differ in their neurophysiological responses during an associative learning paradigm. Male P and NP rats were implanted with electrodes in the frontal cortex, parietal cortex, and amygdala. Both groups were then exposed to an associative learning paradigm. During the first five sessions (conditioning phase), an infrequently presented tone was paired with the delivery of a food pellet. A second tone was also presented during these sessions, but this tone was never paired with food pellet presentation. During the second five sessions (extinction phase), neither of the tones were paired with food pellet presentation. Event‐related potentials (ERPs) in response to the tones were recorded during both phases of the experiment. During the first session, the latency of the N1 and P3 waves from the cortical lead in response to the food‐paired tone was significantly longer in the NP rats than in P rats. In addition, P rats displayed significant increases in the latency of the P2 wave component in the cortex and the P3A wave component in the amygdala in response to changes in the association between food pellet and tone presentation. These data indicate that the P rats were more responsive to changes in the association between food pellet delivery and tone presentation. They also suggest more enhanced associative learning in P rats than in NP rats. This enhanced learning could be an innate trait of P rats or the result of altered learning due to differences in anxiety between P and NP rats.
Ethanol Feeding Does Not Affect the Efficacy or Pharmacokinetics of Azithromycin, Trovafloxacin, or Ceftriaxone in a Rat Model of Pneumococcal Pneumonia
Authors: Preheirn Laurel C. , Olsen Keith M. , Yue Mei , Snitily Mary U. , Gentry Martha J.
Published: May 2006

A rat model of ethanol feeding was used to study the effects of ethanol on antibiotic therapy of pneumococcal pneumonia. Male Sprague‐Dawley rats (150 g) received a liquid diet containing 36% of total calories as ethanol. Controls were pair‐fed a liquid diet without ethanol or received rat chow. Diets began 7 days pre‐ and continued postinfection. Rats were infected transtracheally with type 3 Streptococcus pneumoniae and then treated with azithromycin (50 mg/kg), trovafloxacin (50 mg/kg), or ceftriaxone (100 mg/kg) injected subcutaneously twice daily for 5 days. Antibiotic levels in serum, lung cells, and lavage fluid were measured by HPLC. Ethanol‐ and pair‐fed rats had depressed baseline peripheral neutrophil counts hut were able to generate adequate numbers of peripheral and pulmonary polymorphonuclear leukocytes early in the course of their infection. Ethanol feeding did not alter the pharmacokinetics of azithromycin, trovafloxacin, or ceftriaxone. All three antibiotics were equally effective in curing experimental pneumococcal pneumonia, and survival rates were similar in treated ethanol‐fed and control rats.
Effect of Voltage‐Dependent Calcium Channel Blockers on Ethanol‐Induced β‐Endorphin Release From Hypothalamic Neurons in Primary Cultures
Authors: De Alok , Boyadjieva Nadka Iv. , Sarkar Dipak K.
Published: May 2006

The voltage‐dependent calcium channel (VDCC) has been shown to mediate calcium entry into neurons that regulates neurotransmission in many neuronal cells. Four major types of VDCCs (three high‐voltage‐activated L‐. N‐. and P‐types and one low‐voltage‐activated T‐type) have been identified in neurons. Involvement of the VDCC in ethanol‐stimulated β‐endorphin (β‐EP) release from hypothalamic neurons has not been studied. In the present study, the role of VDCC on basal and ethanol‐induced β‐EP release was determined by using rat fetal hypothalamic cells in primary cultures. Treatments with a 50 mM dose of ethanol for 3 hr increased immunoreactive β‐EP (IR‐β‐EP) release from hypothalamic cells maintained in cultures for 9 days. Ethanol‐induced IR‐β‐EP release was inhibited by a P/Q‐type channel blocker ω‐agatoxin TK (0.1–1 μM). an N‐type channel blocker ω‐conotoxin (0.1‐1 μM), an L‐type blocker nifedipine (1‐10 μM), and a T‐type blocker flunarizine (1‐10 μpM). The minimal effective doses of these blockers that blocked the ethanol response produced no significant effects on basal release of IR‐β‐EP; neither did these doses of the blockers produce any significant effects on cell viability. These results suggest that ethanol‐stimulated IR‐β‐EP release is regulated by extracellular calcium involving β‐, N‐, L‐ and T‐type channels.
Role of Metalloproteinases in Liver Fibrosis
Authors: Rojkind Marcos
Published: May 2006

Collagen deposition in the cirrhotic liver is the result of an imbalance between the amount of collagen produced and that, which is degraded. Although several groups have actively investigated the mechanisms that regulate collagen gene expression in the liver, little is known regarding those involved in the regulation of interstitial collagenases. In this study, we shall express our personal ideas regarding the role of metalloproteinases in collagen degradation in the cirrhotic liver, with special emphasis on the interstitial collagenases and some factors that may limit collagen degradation in vivo.
Serum and Saliva Levels of Sialic Acid Are Elevated in Alcoholics
Authors: Pönniö Maritta , Alho Hannu , Heinälä Pekka , Nikkari Seppo T. , Sillanaukee Pekka
Published: May 2006

Background and Methods:

Recently, sialic acid has been suggested as a potential marker for alcohol abuse. In this study, social drinkers and alcoholics were analyzed with a modified version of Warren's method for sialic acid and traditional markers of alcohol abuse in serum (n= 38; n= 87), saliva (n= 36; n= 29), and urine (n= 37; n= 83), respectively. The alcoholics were participating in an alcohol dependency treatment program and were followed in this study for 5 weeks.

Results:

The sialic acid concentrations in female and male alcoholics were significantly higher in serum (p < 0.001; p < 0.001 respectively) and saliva (p < 0.05; p < 0.05) but not in urine, compared with social drinkers. The diagnostic efficiency of serum sialic acid was higher than that for traditional markers: 77% for female subjects and 64% for male subjects. The corresponding results for saliva were 72% and 53%. The sialic acid concentrations were significantly decreased during the alcohol dependency treatment program (after 5 weeks of treatment) in both females and males.

Conclusions:

This study confirms that serum sialic acid is a valuable marker for detecting and monitoring alcohol abuse. This work also indicates that sialic acid in saliva could be used possibly as a noninvasive marker for alcohol abuse.
Effects of Early Postnatal Alcohol Exposure on Learning in the Developing Rat: Replication With Intubation Method of Delivery
Authors: Lilliquist Michael W. , Highfield David A. , Amsel Abram
Published: May 2006

Early postnatal exposure to alcohol during early development produces deficits in learned persistence, as reflected in the partial reinforcement extinction effect (PREE) in weanling rats, and deficits memory‐based learning, as shown by patterned single alternation (PSA) discrimination learning in preweanling rats. We report a partial replication of these effects using the intubation method instead of artificial rearing. Rat pups were intubated once per day with 4.5 g/kg/day alcohol in a milk‐based diet or control diet on postnatal days (PNDs) 4 to 9, and then assessed for the PREE on PNDs 20 and 21 or PSA learning on PNDs 17 and 18. Compared with previous artificial rearing reports, the intubation method produced healthier and heavier pups, and yielded a consistently lower and less variable blood alcohol levels. Even with the lower alcohol levels, intubation with alcohol eliminated the PREE. Intubation with alcohol had a weaker but still detrimental effect on PSA learning. These results suggest that alcohol exposure during development can produce behavioral deficits in the absence of the more severe effects on brain and body growth typically associated with fetal alcohol syndrome.
Alcoholic Hepatitis as a T‐Cell Mediated Disorder: An Hypothesis
Authors: Batey R. G. , Clancy R. L. , Pang G. T. , Cao Q.
Published: May 2006

Background: The mechanism by which alcohol induces alcoholic hepatitis, the precursor lesion for cirrhosis, has never been elucidated. In particular, direct toxicity has not been proven. This article reviews the hypothesis that a primary target of chronic alcohol ingestion is the T lymphocyte. The lesion in the T lymphocyte is characterized by reduced baseline secretion of cytokines, including tumor necrosis factor‐α; although characterized by an exaggerated release of cytokines when stimulated by polyclonal activators such as endotoxin. High concentrations of cytokines, especially tumor necrosis factor‐α, within the liver induce necrosis/apoptosis of hepatocytes.

Methods: Data supporting this hypothesis in rodent models are reviewed.

Conclusion: A strategic approach for testing this concept in man is defined.
Binge Drinking and Bone Metabolism in a Young Actively Growing Rat Model
Authors: Sampson H. Wayne , Gallager Sharon , Lange Jason , Chondra Whitney , Hogan Harry A
Published: May 2006

Background: Chronic alcohol consumption has been demonstrated to be deleterious to bone health. However, binge drinking is the prevalent form of drinking in young people, which was the impetus for the present study to determine the effect of week‐end and week‐long binge drinking on bone health in a young actively growing animal model.

Methods: Four‐week‐old, female, Sprague‐Dawley rats were given the amount of 5% alcohol by gavage to be equivalent to a 63 kg woman drinking six beers a day for either 2 or 5 consecutive days per week.

Results: There were no changes in the 5‐day binge animals, but the 2‐day binge animals were hypocalcemia Similarly, 2‐day binge animals had slightly increased bone chemistry and histomorphometric values for both tibia and femur, but only femur length, dry weight, and ash weight as well as femur density, presented either as g/ml or ash weight per unit volume, were increased by a statistically significant level. Cross‐section periosteal Mineral Apposition Rate (MAR) was significantly decreased in the 2‐day alcohol fed animals.

Conclusions: Actively growing rats given 5% alcohol by gavage for 2 days per week have an increased bone length, bone weight, and bone density. The interpretation of these results must be viewed with great caution because studies of chronic alcohol consumption, and many studies of acute drinking, clearly indicate deleterious effects of alcohol on bone health. Those fed alcohol for 5 days per week showed no change.
Serotonergic Neuronal Activity in the Dorsal Raphe Nucleus of Selectively Bred Alcohol‐Preferring and Alcohol‐Nonpreferring Rats and Unselected Wistar Rats
Authors: Morzorati Sandra L. , Johnson Timothy B.
Published: May 2006

Background:Selectively‐bred alcohol‐preferring (P) rats have fewer serotonin (5‐HT) neurons in the dorsal raphe nucleus (DRN) than do alcohol‐nonpreferring (NP) rats. The present study was designed to test the hypothesis that the remaining 5‐HT neurons in P rats compensated for their reduced number by increasing neuronal activity.

Methods:Spontaneous activity was recorded from single‐spiking and bursting 5‐HT neurons in the DRN of unanesthetized paralyzed, alcohol‐naive P, NP, and Wistar rats. Firing frequencies, the percentages of action potentials in bursts, and the percentages of bursting neurons were evaluated.

Results:There were no significant differences among the three groups of rats in any of the parameters measured. Power analyses were performed on preliminary data to determine the sample sizes necessary for detection of significant differences. The mean firing frequencies of single‐spiking 5‐HT neurons averaged 1.8 (37 neurons), 1.7 (17 neurons), and 1.8 (41 neurons) spikes per second in P, NP, and Wistar rats, respectively. For bursting 5‐HT neurons, the percentages of action potentials in bursts for P, NP, and Wistar rats were 55.0% (24 neurons), 49.7% (18 neurons), and 55.1% (21 neurons). The mean percentages of bursting 5‐HT neurons encountered per electrode penetration were 44% for P rats (n= 28), 44% for NP rats (n= 14), and 34% for Wistar rats (n= 26).

Conclusions:The results indicate that the sample of 5‐HT neurons recorded in the DRN of P rats had not compensated for a reduced number by altering neuronal activity.
Naltrexone's Effect on Cue‐Elicited Craving Among Alcoholics in Treatment
Authors: Monti Peter M. , Rohsenow Damaris J. , Hutchison Kent E. , Swift Robert M. , Mueller Timothy I. , Colby Suzanne M. , Brown Richard A. , Gulliver Suzy B. , Gordon Alan , Abrams David B.
Published: May 2006

Background: Advancing knowledge of biobehavioral effects of interventions can result in improved treatments. Thus, a standardized laboratory cue reactivity assessment has been developed and validated to assess the cognitive and psychophysiological responses to a simulated high‐risk situation: alcohol cues. The present study investigates the effects of a pharmacotherapy (naltrexone) on a laboratory‐based, cue‐elicited urge to drink among abstinent alcoholics in treatment.

Methods: Alcohol‐dependent subjects were randomized to 12 weeks of naltrexone or placebo after completing a partial hospital program. After ∼ 1 week on medication, all received cue reactivity assessment.

Results: Significantly fewer patients taking naltrexone reported any urge to drink during alcohol exposure than did those on placebo. Those with any urges reported no decrement in level of the urges. Mean arterial pressure decreased significantly for those on placebo, but not for those on naltrexone, whereas cue‐elicited decreases in heart rate were not affected by the medication.

Conclusions: The results have implications for models of relapse and naltrexone's effects. Cue reactivity methodology has utility for investigating hypothesized mediators of therapeutic effects of pharmacotherapies as well as behavioral treatments.
Role of Yeasts in the Salivary Acetaldehyde Production From Ethanol Among Risk Groups for Ethanol‐Associated Oral Cavity Cancer
Authors: Tillonen J. , Homann N. , Rautio M. , Jousimies‐Somer H. , Salaspuro M.
Published: May 2006

Background: Acetaldehyde, the first metabolite of alcohol, has been proposed to be the carcinogenic substance behind ethanol‐related oral cancers. High levels of acetaldehyde are formed from ethanol in saliva by the oral flora, but so far the role of certain microbial species responsible for this phenomenon is not known. Yeasts are common commensals of the oral cavity that have alcohol‐oxidizing enzymes, thus providing a potential source of acetaldehyde from ethanol. The aim of this study was to examine the contribution of oral yeasts to the production of ethanol‐derived acetaldehyde in the oral cavity.

Methods: Fifty‐five saliva samples were divided into two groups, high and low, based on the in vitro salivary acetaldehyde production capacity from ethanol. Yeasts were isolated and identified from these samples, and their acetaldehyde production capacity was determined gas chromatographically by incubating intact cells with ethanol at the physiological pH of 7.4.

Results: Yeast colonization was found in 78% of the high acetaldehyde‐producing salivas, compared with 47% in the low acetaldehyde‐producing salivas (p = 0.026). Among carriers, the density of yeasts was higher in the high than in low acetaldehyde producers (p = 0.025). Candida albicans was the main species isolated (88% of all oral isolates). Moreover, C. albicans strains isolated from the high acetaldehyde‐producing salivas formed significantly higher acetaldehyde levels from ethanol than C. albicans strains from low‐acctaldehyde‐producing salivas (73.1 nmol ach/10e6 colony‐forming units vs. 43.2 nmol ach/10e6 colony‐forming units, p= 0.035).

Conclusions: This study shows that some C. albicans strains have a marked capacity to produce toxic and carcinogenic acetaldehyde from ethanol in vitro. Because the in vitro production of salivary acetaldehyde has been previously shown to correlate with in vivo acetaldehyde production, our finding could be an important microbial pathogenetic factor underlying cancer of the oral cavity associated with ethanol drinking.
Genetic Association Between Alcohol Withdrawal Symptoms and Polymorphism of CCK Gene Promoter
Authors: Okubo Takehito , Harada Shoji , Higuchi Susumu , Matsushita Sachio
Published: May 2006

In the central nervous system, cholecystokinin (CCK) is an important neurotransmitter that gives the influences on firings, anxiety, notiception, and dopamine‐related behavior. CCK co‐exists in the dopaminergic neurons, interacting with dopamine. In this study, we examined the genetic variant −45 C to T substitution of the CCK gene promoter region among 195 healthy Japanese and 174 patients with alcohol withdrawal syndrome (52 delirium tremens, 39 hallucinosis, 20 seizures, and 92 lack of these symptoms) by using polymerase chain reaction‐based single‐strand conformational polymorphism analysis. Patients with delirium tremens showed a significantly higher frequency of the variant, compared with the controls (X2= 4.91, p < 0.03), but patients with other symptoms showed no difference. These data suggested that the individuals possessing allelic mutation (−45T) in the promoter region of the CCK gene might be susceptible to delirium tremens caused by alcohol abuse.
Genetic Polymorphism of Aldehyde Dehydrogenase 2 in Patients With Upper Aerodigestive Tract Cancer
Authors: Tanabe Hiroki , Ohhira Motoyuki , Ohtsubo Tikara , Watari Jiro , Yokota Kinichi , Kohgo Yutaka
Published: May 2006

Background: Alcohol consumption is one of the major risk factors of the upper aerodigestive tract (UADT) cancers, and combined cancers are frequently discovered in the patients with UADT cancer. The association between esophageal cancer and alcohol‐related metabolizing enzymes is well studied, but only a few examinations about the association between head and neck cancer and the enzymes were performed.

Methods: Fifty‐two patients with UADT cancer (head and neck cancer in 25, esophageal cancer in 19, and multiple cancers in 8) were examined in the alcohol habit and in the polymorphisms of aldehyde dehydrogenase 2 (ALDH2) and cytochrome P‐4502E1.

Results: Patients with multiple cancers had significantly higher ethanol consumption than the other two groups (p < 0.001). The frequency of ALDH2* 1/2*2 heterozygote was significantly lower (p= 0.009) in patients with head and neck cancer (5/25) than patients with esophageal cancer (11/19). The allele frequency of P‐4502E1 did not show a significant difference between the groups (p= 0.700).

Conclusions: These results demonstrated the difference in the frequency of ALDH2 heterozygote between the patients with esophageal cancer and patients with head and neck cancer.
Increase in Beating Rate of Cultured Chick Cardiac Myocytes by Ethanol and Inhibition of the Increase by Antiarrhythmic Drugs
Authors: Nakamura Kazufumi , Kouchi Hirosuke , Ohe Tohru , Namba Masayoshi
Published: May 2006

Drinking alcohol sometimes causes cardiac arrhythmia, but the precise mechanism remains unknown. To study the mechanism, we investigated the effects of ethanol exposure on the beating rate of cultured chick cardiac myocytes. Primary cultures of cardiac myocytes were prepared from the ventricles of 14‐day‐old chick embryos and then treated with ethanol which, in the range of 0.3 to 1.5 vol%, increased the beating rate in a dose‐dependent manner. Ethanol (0.6 vol%) caused an increase in the beating rate, but disopyramide (5 μg/ml) and procainamide (10 μg/ml), Na+ and K+ channel blockers, inhibited the increase in the beating rate significantly. Neither lidocaine (5 μg/ml) nor mexiletine (2 μg/ml), Na+ channel blockers, nor calcium antagonist verapamil (5 ng/ml) inhibited the increase. However, tetraethylammonium chloride (ranging from 15 to 30 mmol/1), a K+ channel blocker, inhibited the increase. These findings indicate that ethanol increases the beating rate of cultured chick cardiac myocytes via the activation of the K+ channel. This experimental model may be useful in studying the effect of ethanol on the K+ channel.
Quantitative Trait Loci Affecting Ethanol Sensitivity in BXD Recombinant Inbred Mice
Authors: Browman Kaitlin E. , Crabbe John C.
Published: May 2006

Background:

Genetic and environmental factors contribute to an individual's sensitivity to ethanol, although the exact genes underlying ethanol's effects are not known. Quantitative trait locus (QTL) mapping is one successful method for provisionally identifying genes participating in the mediation of a given behavior. QTL analyses seek to identify associations between a quantitative response and previously mapped marker genes across genetically diverse individuals. Many QTL analyses have been performed in BXD recombinant inbred (RI) strains of mice derived from a cross of C57BL/6J (B6) and DBA/2J (D2) progenitor strains.

Methods:

We conducted a QTL analysis of ethanol‐induced loss of righting reflex and ataxia using a panel of 25 BXD RI strains and the progenitors B6 and D2. We measured the duration of loss of righting reflex after injection and blood ethanol concentrations upon regaining of righting reflex. Ataxia was measured as the latency to fall from a vertical screen.

Results:

Genome‐wide QTL analyses correlating strain means with allelic status at >1500 markers identified several associations (p≤ 0.01). These provisional QTLs were on all chromosomes except 2,5,12,13, and X, and several map near potential candidate genes.

Conclusions:

These results suggest that ethanol sensitivity is determined by the actions of multiple genes and further suggest their general chromosomal map locations. These provisional linkages will now be confirmed or rejected using additional genetically segregating populations.
Comparison of Cross‐Sectional and Daily Reports in Studying the Relationship Between Depression and Use of Alcohol in Response to Stress in College Students
Authors: Flynn Heather A.
Published: May 2006

Background:

Alcohol use in response to stress in college students may be affected by the presence of symptoms of depression. However, this is a challenging issue to study due to the various methodologies used as well as the possible effect of depressed mood on the accuracy of self‐report. This study focused on methodological issues as possible sources of equivocal findings regarding the relationship between depressed mood and alcohol use in response to stress in a college student population. Findings may differ when these variables are examined cross‐sectionally versus longitudinally.

Methods:

Depressed mood and alcohol coping were assessed both cross‐sectionally and repeatedly over time in 125 college students. Participants were assessed at baseline using a diagnostic self‐report measure of depression as well as a measure of typical coping style. In addition, daily measures of stress, symptoms of depression, and coping were completed for 45 consecutive days.

Results:

Different relationships between depressed mood and alcohol coping were found when depressed individuals were analyzed separately from those who were not depressed. Although a significant correlation between daily use of alcohol coping and daily depressed mood was found, there were no differences between depressed and nondepressed participants (as assessed at baseline) on daily alcohol coping.

Conclusions:

These findings have implications for research design as well as clinical assessment regarding the relationships between mood and use of alcohol for coping; the findings suggest that cross‐sectional measures of mood and alcohol use may obscure differences as assessed repeatedly over time. In addition, these findings support the utility of frequent assessment of depressive symptoms when implementing or evaluating programs that target coping skills in college students.
Differential Effects of Ethanol on Signal Transduction
Authors: Levine Gail H. , Maglio Jeff J. , Horwitz Joel
Published: May 2006

Background:

PC12 pheochromocytoma cells were used as a model to study the effect of long‐term ethanol exposure on signal transduction systems. In PC12 cells, the agonist bradykinin stimulates a phospholipase C specific for inositol‐containing phospholipids and a phospholipase D specific for phosphatidylcholine.

Methods:

PC12 cells were grown in monolayer and cultured in the presence and absence of 1% ethanol for 5 days. After this period, bradykinin‐stimulated phospholipase C and D were measured. The effect of long‐term ethanol on the bradykinin‐mediated activation of mitogen‐activated protein (MAP) kinase was also measured.

Results:

In cells exposed to 1% ethanol for 5 days, bradykinin‐stimulated phospholipase D was greatly attenuated, whereas bradykinin‐stimulated phospholipase C was not altered. The tyrosine kinase inhibitor, genistein, blocked the bradykinin‐mediated activation of phospholipase D but did not affect the stimulation of phospholipase C. However, long‐term ethanol treatment did not attenuate the ability of bradykinin to activate MAP kinase, which suggests that ethanol did not have a general effect on all tyrosine kinase pathways.

Conclusions:

Ethanol has a differential effect on signal transduction in PC12 cells. Activation of phospholipase D may be mediated by a kinase, whereas the activation of phospholipase C is probably mediated by the guanine nucleotide binding protein, Gq. Because of these differences in activation mechanism, the pathways may adapt differently to long‐term exposure to ethanol.
Effect of Hormone Balance on Carbohydrate‐Deficient Transferrin and Gamma‐Glutamyltransferase in Female Social Drinkers
Authors: Sillanaukee Pekka , Alho Hannu , Strid Nuria , Jousilahti Pekka , Vartiainen Erkki , Olsson Ulf , Sillanaukee Päivi
Published: May 2006

Background:

Carbohydrate‐deficient transferrin (CDT) and γ‐glutamyltransferase (GGT) are the most commonly used markers for alcohol abuse, but their sensitivity and specificity are lower and have different reference values among females compared with males. In the present study, we evaluated the effect of women's hormone balance on these two alcohol markers, as well as on their mathematical combination, named γ‐CDT.

Methods:

An age‐stratified random sample of 3962 women, between 25–74 years old, was drawn from the normal population. Pregnancy, the use of oral contraceptives, intrauterine device for contraception, hormone replacement therapy, and hormone treatment for infertility were considered. A comparison between fertile, peri‐ and postmenopausal women was also done.

Results:

Existing pregnancy increased CDT levels but decreased GGT values. Lower CDT and higher GGT levels were observed among those women using oral contraceptives and in postmenopausal women compared with women at the fertile stage. γ‐CDT was not influenced by hormone balance.

Conclusions:

The different hormonal status had an opposite effect on CDT and GGT. Women who were close to late menopause had levels of both markers closer to the values of men. It must be pointed out that the findings presented here are based on measurements of absolute CDT values and that no measurements of total transferrin were done. γ‐CDT, not influenced by hormone balance, indicates promising clinical utility among women.