bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peroxisome Proliferator‐Activated Receptors (PPAR) and the Mitochondrial Aldehyde Dehydrogenase (ALDH2) Promoter In Vitro and In Vivo
Authors: Crabb David W. , Pinaire Jane , Chou Wan‐Yin , Sissom Sean , Peters Jeffrey M. , Harris Robert A. , Stewart Mark 
Published: April 2006

Background : The aldehyde dehydrogenase 2 (ALDH2) promoter contains a nuclear receptor response element (NRRE) that represents an overlapping direct repeat‐1 (DR‐1) and ‐5 (DR‐5) element. Because DR‐1 elements are preferred binding sites for peroxisome proliferator‐activated receptors (PPARs), we tested the hypothesis that PPARs regulate ALDH2 expression.Methods: We examined the ability of PPAR isoforms to bind to the ALDH2 NRRE in electrophoretic mobility shift assays, their ability to activate the transcription of promoter‐reporter constructs containing this NRRE, the effect of PPAR ligands on ALDH2 expression in liver, and the role of the PPARα on the expression of ALDH2 by using PPARα‐null mice.Results: In vitro translated PPARs bound the ALDH NRRE with high affinity. Mutation of the NRRE indicated that binding was mediated by the DR‐1 element. Cotransfection of PPAR expression plasmids showed that PPARα had no effect on expression of heterologous promoter constructs containing the NRRE. PPARγ slightly induced expression, whereas PPARδ repressed basal activity of the promoter and blocked induction by hepatocyte nuclear factor 4. Treatment of rats with the PPAR ligand clofibrate repressed expression of ALDH2 in rats fed either stock rodent chow or a low‐protein diet. Consistent with the transfection data, expression of ALDH2 protein was not different in PPARα‐null mice. Treatment of the mice with the PPARα agonist WY14643 slightly decreased the level of ALDH2 protein in both wild‐type and PPARα‐null mice, suggesting that the effect of WY14643 was not mediated by the receptor.Conclusions: These data indicate that ALDH2 is not part of the battery of lipid metabolizing enzymes and proteins regulated by PPARα
Psychopathology in Pregnant Drug‐Dependent Women With and Without Comorbid Alcohol Dependence
Authors: Miles Donna R. , Svikis Dace S. , Kulstad Jody L. , Haug Nancy A. 
Published: April 2006

Background : Individuals with comorbid alcohol and drug use disorders are at particularly high risk for a variety of problems, including other psychiatric disorders. In general, patients with comorbid alcohol and drug dependence tend to have more severe dependence problems and often have poorer treatment outcomes than individuals with single disorders. For treatment‐seeking pregnant women, psychiatric comorbidity can lead to relapse and premature treatment dropout, with adverse consequences to mother and infant.Methods: Psychopathology, as measured by the Minnesota Multiphasic Personality Inventory–Revised (MMPI‐2), was examined in 170 pregnant women admitted to a comprehensive treatment program for cocaine or opiate dependence. Most were single (75%) and African American (80%), with a mean age of 29 years. Thirty‐six met DSM‐III‐R criteria for both alcohol and drug dependence (alcohol positive), whereas 134 were drug dependent only (alcohol negative).Results: Alcohol‐positive women had higher levels of psychopathology than alcohol‐negative women, with higher scores on scales 2 (Depression), 4 (Psychopathic Deviance), 8 (Schizophrenia), and 0 (Social Introversion;p < 0.05). The mean MMPI‐2 profile for alcohol‐positive women was 2‐4‐8 (Depression‐Psychopathic Deviance‐Schizophrenia; all T‐scores > 65), whereas alcohol‐negative women had only a scale 4 increase.Conclusions: Results suggest that pregnant, drug‐dependent women with comorbid alcohol dependence present for treatment with greater psychopathology and thus may require more intense interventions than pregnant, drug‐dependent women without comorbid alcohol dependence. Alcohol use by pregnant women is particularly important to address in treatment, because alcohol is a known teratogen associated with mental retardation and behavioral problems.
Effect of Chronic Ethanol Exposure on Female Rat Reproductive Cyclicity and Hormone Secretion
Authors: Emanuele N. V. , LaPaglia N. , Steiner J. , Kirsteins L. , Emanuele M. A. 
Published: April 2006

Background : Ethanol exposure impairs mammalian reproductive function. However, the mechanisms are not fully understood.Methods: Adult female rats were given an ethanol or a calorically matched control diet. A third group was given a liquid nonethanol diet. Half the animals were killed at 2 weeks (short chronic) and the other half at 2 months (long chronic), all on the day of proestrous on the basis of daily vaginal smears.Results: The major effect of ethanol feeding was disruption in the estrous cycle. Although all of the pair‐fed animals continued to cycle, 40% of the ethanol rats in the short chronic study had disruption of their cycles. In the long chronic study, 83% of the ethanol animals had abnormal cycling, in contrast to 16% of the pair‐fed controls. The nature of the cycle disruption was prolongation of diestrous, with an increased time interval between proestrous surges. In four ethanol‐fed rats, there was complete cessation of the estrous cycle. However, ethanol did not decrease ovarian or uterine weight. Ethanol significantly increased serum estradiol in the short chronic but not long chronic study, whereas progesterone was unchanged. Ethanol did cause a significant reduction in circulating insulin‐like growth factor.Conclusions: The major effect of both short chronic and long chronic ethanol exposure was disruption of the estrous regularity, leading to a decreased number of proestrous surges. Part of the mechanism of this disruption might be a transient estrogen increase or a decrease in circulating insulin‐like growth factor.
Alcohol‐Mediated Purkinje Cell Loss in the Absence of Hypoxemia During the Third Trimester in an Ovine Model System
Authors: West James R. , Parnell Scott E. , Chen Wei‐Jung A. , Cudd Timothy A. 
Published: April 2006

Background : Although the mechanisms that underlie fetal alcohol‐induced neuronal loss have not been determined, hypoxia/hypoxemia has been considered a leading candidate. This study was designed to test the hypothesis that neuronal loss could occur in the developing brain in the absence of fetal hypoxemia.Methods: Three groups of pregnant sheep were used: a control group, a binge‐drinking group, and a pair‐fed group. The alcohol and pair‐fed animals were anesthetized on day 113 of pregnancy, and the mothers and fetuses were instrumented with arterial and venous catheters. All animals were killed on day 133. Stereological cell counting techniques were used to estimate the total number of Purkinje cells in the fetal cerebellum.Results: Peak maternal and fetal blood alcohol concentrations did not produce fetal hypoxemia. Nevertheless, there was a 25% loss of Purkinje cells of the cerebellum in the alcohol‐exposed fetuses compared with that in the pair‐fed controls. The loss of neurons was not accompanied by microencephaly or a concomitant decrease in either cerebellar weight or volume of the fetal cerebellum.Conclusions: Neuronal loss can be observed after alcohol exposure during the third trimester equivalent in fetal sheep in the absence of alcohol‐induced hypoxemia. Furthermore, cell loss in the absence of deficits in gross brain weight or regional brain volume indicates that the lack of gross brain volume deficits from magnetic resonance imaging techniques is not a reliable indication that the brain is unaffected by the alcohol exposure.
Nicotine Decreases Blood Alcohol Concentration in Neonatal Rats
Authors: Chen Wei‐Jung A. , Parnell Scott E. , West James R. 
Published: April 2006

Background : Our previous findings suggested that the intragastric coadministration of alcohol and nicotine to neonatal rats resulted in a significant decrease from the predicted peak blood alcohol concentration (BAC). We hypothesized that the coadministration of alcohol and nicotine would produce a nicotine dose–related decrease in peak BAC and a change in the BAC time curve profile.Methods: Sprague‐Dawley rat pups were given alcohol and nicotine simultaneously via intragastric infusion. Two sets of nicotine doses were used in two independent studies. The low doses of nicotine were examined after the study of high doses of nicotine administration because of the possible ceiling effects from these nicotine doses on lowering BACs.Results: The results not only confirmed that the peak BAC was lowered by nicotine, but also generated new findings showing that the profile of BAC time curve was affected by these doses of nicotine. Concerns about possible ceiling effects led us to conduct another experiment to examine the effects of lower doses of nicotine on BACs. Those results showed a significant decline in BACs after cotreatment with 0.5 or 1 mg/kg nicotine and less robust changes on the BAC curve profiles. Although the nicotine dose at 0.25 mg/kg/day did not affect significantly the overall BAC profile, it did lower the peak BAC.Conclusions: Nicotine is capable of lowering the peak BAC among neonatal rat pups. Furthermore, the pattern of the BAC time curve seems to be more affected by high doses of nicotine.
Effect of Chronic Ethanol Ingestion on Alveolar Type II Cell: Glutathione and Inflammatory Mediator‐Induced Apoptosis
Authors: Brown Lou Ann S. , Harris Frank L. , Bechara Rabih , Guidot David M. 
Published: April 2006

Background : In septic patients, chronic alcohol abuse increases the incidence of the acute respiratory distress syndrome, a syndrome that requires alveolar type II cell proliferation and differentiation for repair of the damaged alveolar epithelium. We previously showed in a rat model that chronic ethanol ingestion decreased the antioxidant glutathione (GSH) in type II cells and exacerbated endotoxin‐mediated acute lung injury. We hypothesized that this GSH depletion by ethanol, particularly mitochondrial GSH, predisposed type II cells to inflammatory mediator‐induced apoptosis.Methods: Adult male rats were fed the Lieber‐DeCarli diet for 2, 6, or 16 weeks. Alveolar type II cells were then isolated and treated with hydrogen peroxide or TNF‐α. The effect on glutathione (cytosolic and mitochondrial), apoptotic events, and necrosis were determined. In other studies, rats were fed ethanol for 6 weeks and were treated with endotoxin and apoptosis of type II cells determined by the TUNEL method.Results: Chronic ethanol ingestion alone resulted in a progressive decrease in mitochondrial GSH and a progressive increase in the basal apoptosis and necrosis rate (p≤ 0.05). Furthermore, there was a progressive increase in the sensitivity of the cells to H2O2 or TNF‐α induced cytochrome c release, caspase 3 activation, apoptosis, and necrosis (p≤ 0.05). Finally, there was a 2‐fold increase in apoptotic type II cells in vivo when chronic ethanol ingestion was superimposed on endotoxemia.Conclusions: These results suggested that chronic ethanol ingestion resulted in a progressive depletion of mitochondrial GSH and sensitization of type II cells to inflammatory mediator‐induced apoptosis and necrosis. These effects may be particularly relevant during acute stress when proliferation and differentiation of these cells are critical to repair of the damaged alveolar epithelium and may have important ramifications for the treatment of acute respiratory distress syndrome in patients with a history of alcohol abuse.
Induction and Maintenance of Ethanol Self‐Administration in Cynomolgus Monkeys (Macaca fascicularis): Long‐Term Characterization of Sex and Individual Differences
Authors: Vivian J. A. , Green H. L. , Young J. E. , Majerksy L. S. , Thomas B. W. , Shively C. A. , Tobin J. R. , Nader M. A. , Grant K. A. 
Published: April 2006

Background: Investigations of oral ethanol self‐administration in nonhuman primates have revealed important parallels with human alcohol use and abuse, yet many fundamental questions concerning the individual risk to, and the biological basis of, excessive ethanol consumption remain unanswered. Moreover, many conditions of access to ethanol in nonhuman primate research are largely unexplored. This set of experiments extends within‐ and across‐session exposure to ethanol to more fully characterize individual differences in oral ethanol self‐administration.Methods: Eight male and eight female adult cynomolgus monkeys (Macaca fascicularis) were exposed to daily oral ethanol self‐administration sessions for approximately 9 months. During the first 3 months, a fixed‐time (FT) schedule of food delivery was used to induce the consumption of an allotted dose of ethanol in 16‐hr sessions. Subsequently, the FT schedule was suspended, and ethanol was available ad libitum for 6 months in 16‐ or 22‐hr sessions.Results: Cynomolgus monkeys varied greatly in their propensity to self‐administer ethanol, with sex and individual differences apparent within 10 days of ethanol exposure. Over the last 3 months of ethanol access, individual average ethanol intakes ranged from 0.6 to 4.0 g/kg/day, resulting in blood ethanol concentrations from 5 to 235 mg/dl. Males drank approximately 1.5‐fold more than females. In addition, heavy‐, moderate‐, and light‐drinking phenotypes were identified by using daily ethanol intake and the percentage of daily calories obtained from ethanol as criteria.Conclusions: Cynomolgus monkeys displayed a wide intersubject range of oral ethanol self‐administration with a procedure that used a uniform and prolonged induction that restricted early exposure to ethanol and subsequently allowed unlimited access to ethanol. There were sex and stable individual differences in the propensity of monkeys to consume ethanol, indicating that this species will be important in characterizing risk factors associated with heavy‐drinking phenotypes.
Role of Nitric Oxide in Ethanol‐Induced Up‐Regulation of Muscarinic Acetylcholine Receptors in SH‐SY5Y Cells
Authors: Caron Murielle H. , Alling Christer 
Published: April 2006

Background: Ethanol abuse has been shown to up‐regulate muscarinic acetylcholine receptors (mAChRs) in the central nervous system, both in vivo and in vitro, but the detailed mechanisms for this action are not known. Recent studies suggest that the actions of ethanol in several biological systems involve nitric oxide (NO) pathways. The aim of this work was therefore to determine whether the effects of long‐term ethanol treatment on mAChRs involved actions upon NO pathways in a well defined cell culture system.Methods: Human neuroblastoma SH‐SY5Y cells were used as an in vitro model system. The time‐ and dose‐dependent effects of ethanol on endogenous NO production, as well as the effects of the NO donor 3‐morpholino‐sydnonimine‐chloride and of the neuronal NO synthase (nNOS) inhibitor Nω‐propyl‐l‐arginine on mAChR number and on ethanol effects upon these receptors, were studied.Results: Ethanol time‐ and dose‐dependently decreased the production of NO in the cells. Exogenous NO decreased the number of mAChRs and totally blocked the effects of ethanol upon these receptors. Inhibition of nNOS up‐regulated the number of mAChRs, but this effect was not additive to the effects of ethanol.Conclusions: The results of this study suggest that the number of cell‐surface mAChRs in SH‐SY5Y cells may be correlated with changes in NO levels. The number of cell surface mAChRs decreased with NO‐elevating treatment and increased with NO‐lowering treatment. Because ethanol, which is known to up‐regulate mAChRs in SH‐SY5Y cells, also decreased NO levels and because nNOS inhibition and ethanol effects on mAChRs were not additive, it is conceivable that ethanol‐induced up‐regulation of mAChRs involves inhibition of nNOS.
Alterations in Central Preproenkephalin mRNA Expression After Chronic Free‐Choice Ethanol Consumption by Fawn‐Hooded Rats
Authors: Cowen Michael S. , Lawrence Andrew J. 
Published: April 2006

Background: Neurotransmission mediated via opioid and dopamine receptors is believed to be involved in the reinforcing and/or rewarding effects of ethanol consumption. We previously examined the effect of ethanol consumption (and naltrexone treatment, used clinically to treat alcoholism) on μ‐opioid receptor density. We describe here the effect of free‐choice ethanol consumption and naltrexone treatment on preproenkephalin, preprodynorphin, and dopamine D1 and D2 receptor mRNA expression in the central nervous system.Methods: Fawn‐hooded rats were given continual free‐choice access to a 5% ethanol solution or water (4 weeks) followed by 2 weeks of water alone. At the end of this abstinence period, osmotic minipumps were implanted subcutaneously to deliver saline (n= 4) or naltrexone (n= 4; 8.4 mg/kg/day for 4 weeks). After recovery from surgery, the rats again were given access to 5% ethanol under the same free‐choice conditions (4 weeks). A third group of age‐matched controls drank only water during the behavioral trial. At the end of the behavioral trial, the rats were decapitated, and a quantitative examination of peptide precursor mRNAs was made by using in situ hybridization histochemistry.Results: Naltrexone treatment significantly decreased preprodynorphin expression in the nucleus accumbens, but neither naltrexone treatment nor ethanol consumption significantly affected dopamine D1 and D2 receptor mRNA expression. In contrast, ethanol consumption increased preproenkephalin mRNA in the central and intercalated nuclei of the amygdala but decreased preproenkephalin mRNA in the nucleus accumbens and olfactory tubercle. The decreased level of preproenkephalin mRNA in the nucleus accumbens may reflect a neuroadaptive response to increased release of dopamine, whereas the increased level of preproenkephalin mRNA in the central nucleus of the amygdala may be associated with an anxiolytic effect of ethanol consumption.Conclusions: The data support the putative role of opioid peptides in the effects of ethanol and suggest that the nucleus accumbens and central nucleus of the amygdala are loci for the reinforcing effects of ethanol.
Effects of Concurrent Access to Multiple Ethanol Concentrations and Repeated Deprivations on Alcohol Intake of Alcohol‐Preferring Rats
Authors: Rodd‐Henricks Zachary A. , Bell Richard L. , Kuc Kelly A. , Murphy James M. , McBride William J. , Lumeng Lawrence , Li Ting‐Kai 
Published: April 2006

Background: The alcohol deprivation effect (ADE) is a temporary increase in the voluntary intake of ethanol solutions following a period of alcohol deprivation. Multiple deprivations can prolong the expression of an ADE. This study examined the effects of initial deprivation length, concurrent exposure to multiple ethanol concentrations, and number of deprivation exposures on the magnitude and duration of the ADE in alcohol‐preferring (P) rats.Methods: Adult female P rats received 24‐hr free‐choice access to 10, 20, and 30% ethanol and water for 6 weeks. Rats were then randomly assigned to three groups; one group served as a nondeprived control, whereas the other two groups were initially deprived of ethanol for 2 or 8 weeks. The ethanol solutions were restored to both deprived groups for 2 weeks before the groups were deprived of ethanol for another 2 weeks. This cycle was repeated three times for a total of four deprivations.Results: After the initial ethanol deprivation period, both deprived groups displayed a similar 2‐fold increased ethanol intake (g/Kg/day) during the initial 24‐hr period when ethanol was restored. Both deprived groups showed greater than 2‐fold increases in intake of the 20 and 30% ethanol solutions after re‐exposure. Ethanol consumption returned to baseline levels within 2 weeks, before the subsequent deprivation period. Multiple deprivations increased the magnitude of the ADE over that observed in the first deprivation during the initial 24‐hr period of re‐exposure and prolonged the duration of the ADE. In addition, repeated deprivations increased ethanol intake in the first 2‐hr period of re‐exposure and produced blood ethanol levels in excess of 150 mg/100 ml.Conclusions: Alterations in the reinforcing and/or aversive effects of alcohol occurred after a single prolonged deprivation and were enhanced with repeated deprivations.
Effect of Tryptophan Depletion on Alcohol Cue‐Induced Craving in Abstinent Alcoholic Patients
Authors: Petrakis Ismene L. , Trevisan Louis , Boutros Nashaat N. , Limoncelli Diana , Cooney Ned L. , Krystal John H. 
Published: April 2006

Background: The capacity of alcohol cues to precipitate the desire to drink may be an important determinant of relapse to alcohol use in recovering alcohol‐dependent patients. This study evaluated whether attenuation of serotonin synthesis via depletion of its precursor tryptophan reduces the magnitude of cue‐induced craving for alcohol in recently abstinent alcoholic individuals.Methods: Alcohol‐dependent patients (n= 16), 1 to 3 months after detoxification, who exhibited a 20% or greater increase in reported craving when presented with an alcoholic beverage, completed two additional alcohol cue‐exposure test days, 1 week apart. Each cue exposure was preceded by administration of a concentrated amino acid drink that resulted in a rapid and significant decline in plasma free tryptophan (active depletion, no tryptophan supplementation) or a similar drink containing tryptophan (placebo depletion). Tests were conducted in a randomized, double‐blind fashion.Results: There were no significant changes in the magnitude of cue‐induced craving with active tryptophan depletion compared with placebo.Conclusions: These data question the dependence of alcohol cue‐induced craving in sober alcoholics on the ongoing synthesis of serotonin.
The Critical Dimension of Ethnicity in Liver Cirrhosis Mortality Statistics
Authors: Stinson Frederick S. , Grant Bridget F. , Dufour Mary C. 
Published: April 2006

Background: In 1997, liver cirrhosis was the 10th leading cause of death in the United States. Beginning in the 1950s, liver cirrhosis mortality rates have been consistently higher for black than for white men and women. There has been a gradual adoption of the recommendation that all death certificates include information on the Hispanic origin of decedents, with universal adoption in the 1997 data year. It is the purpose of this study to examine the extent to which relative risks for cirrhosis mortality might shift for different demographic groups when Hispanic origin is considered along with the race and sex of the decedent.Methods: Age‐adjusted death rates were calculated for liver cirrhosis by using public‐use data files produced by the National Center for Health Statistics. Trends in cirrhosis mortality rates from 1991 through 1997 are shown for white Hispanic, white non‐Hispanic, black Hispanic, and black non‐Hispanic men and women.Results: In 1997, white Hispanic men show the highest cirrhosis mortality rates over the period examined, followed by black non‐Hispanic and white non‐Hispanic men, white Hispanic women, and black non‐Hispanic and white non‐Hispanic women. Among Hispanic decedents, the largest group was of Mexican ancestry, with large numbers being born outside the United States and having low education levels.Conclusions: The findings of higher risk for cirrhosis mortality among white men and women of Hispanic origin serve to focus new attention on these demographic groups. Collateral analyses of other causes of death do not support alternate explanations of these findings as artifacts of demographic misclassification. Future studies of amounts and patterns of alcohol consumption should include Hispanic origin among demographic factors examined.