bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardioprotective Effect of Propranolol From Alcohol‐Induced Heart Muscle Damage as Assessed by Plasma Cardiac Troponin‐T
Authors: Patel Vinood B. , Ajmal Raheela , Sherwood Roy A. , Sullivan Andrew , Richardson Peter J. , Preedy Victor R. 
Published: April 2006

Background: Heavy alcohol consumption from either long‐term misuse or binge drinking is associated with poor cardiac contractility, mitochondrial dysfunction, and ventricular arrhythmias. The aim of this study was to measure circulating cardiac troponin‐T as a marker for myocardial damage following acute and chronic alcohol administration.Methods: In acute studies, male Wistar rats were treated with alcohol (75 mmol/kg body weight, intraperitoneal) and plasma was collected 2.5 hr after alcohol administration for analysis of rat cardiac troponin‐T. In addition, rats were pretreated with cyanamide (an inhibitor of acetaldehyde dehydrogenase), various beta‐blockers, xanthine oxidase inhibitors, or lisinopril before acute alcohol dosing. In chronic studies, rats were fed alcohol (as 35% of total dietary calories) for 6 weeks.Results: The results of the time course study showed that acute alcohol administration significantly raised plasma cardiac troponin‐T levels after 2.5 hr and 6 hr, but not after 24 hr. The effects of alcohol on cardiac troponin‐T were potentiated with cyanamide pretreatment. Acute ethanol, alone or with cyanamide pretreatment, decreased systolic blood pressure and increased heart rates. Beta‐blocker pretreatment with propranolol reduced the alcohol‐induced increase in plasma troponin‐T, whereas lisinopril potentiated this effect. The beta‐blockers, atenolol and metoprolol, and the xanthine oxidase inhibitors, allopurinol and oxypurinol, were unable to reduce elevated troponin‐T. However, pretreatment with the beta‐blocker timolol moderated the acute alcohol‐induced increase in troponin‐T. In the chronic alcohol rat model, no differences were observed between alcohol and control pair‐fed rats, suggesting the inducement of tolerance.Conclusions: In conditions of acute exposure, ethanol‐induced lesions are characterized by raised plasma cardiac troponin‐T possibly due to β1 and/or β2 adrenergic activation.
Effects of Prenatal Ethanol Exposure on Hypothalamic‐Pituitary‐Adrenal Regulation After Adrenalectomy and Corticosterone Replacement
Authors: Glavas Maria M. , Hofmann Candace E. , Yu Wayne K. , Weinberg Joanne 
Published: April 2006

Background: Previous studies have demonstrated that rats prenatally exposed to ethanol (E) exhibit hypothalamic‐pituitary‐adrenal (HPA) hyperresponsiveness, demonstrated by increased and/or prolonged elevations of adrenocorticotropin (ACTH) and/or corticosterone (CORT) after stress. This study investigated possible mechanisms of HPA hyperresponsiveness in E rats by manipulating CORT feedback regulation of HPA activity via adrenalectomy (ADX) with or without CORT replacement.Methods: Male Sprague‐Dawley rat offspring from prenatal E, pair‐fed (PF) and ad libitum–fed control (C) groups were tested at 90 to 120 days of age. Rats were either sham‐operated or underwent ADX, with or without CORT replacement. CORT (25 μg/ml) was replaced via the drinking water to achieve basal plasma CORT levels and maintain a phasic CORT signal. Seven days after surgery, animals were decapitated at the diurnal peak either under basal conditions or after a 15‐min restraint stress, and trunk blood was collected.Results: After ADX, loss of the CORT feedback signal resulted in increased plasma ACTH in all groups compared with those in sham animals. In addition, under basal conditions, ADX E rats had significantly greater plasma ACTH levels than both PF and C rats. However, no differences were seen in ADX rats after stress. CORT replacement after ADX was partially effective in normalizing ACTH levels under both basal and stress conditions, with no differences among E, PF, and C animals.Conclusions: These results suggest that E males may exhibit enhanced stimulatory inputs to the hypothalamus, increased pituitary sensitivity to secretagogues, or both, which may be revealed after ADX. In contrast, E animals seem similar to controls in their ability to use an exogenous CORT signal to regulate HPA activity.
Mitochondrial DNA Damage and Impaired Mitochondrial Function Contribute to Apoptosis of Insulin‐Stimulated Ethanol‐Exposed Neuronal Cells
Authors: de la Monte Suzanne M. , Wands Jack R. 
Published: April 2006

Background: Ethanol inhibition of insulin signaling may contribute to impaired central nervous system development in fetal alcohol syndrome. An important consequence of ethanol inhibition of insulin signaling is increased apoptosis due to reduced levels of insulin‐stimulated phosphoinositol‐3‐kinase activity.Methods: We used viability assays, end‐labeling, Western blot analysis, and MitoTracker (Molecular Probes, Eugene, OR) fluorescence labeling to determine whether ethanol‐induced central nervous system neuronal cell death was mediated in part by increased mitochondrial (Mt) DNA damage and impaired Mt function.Results: In ethanol‐exposed, insulin‐stimulated PNET2 central nervous system–derived human neuronal cells, reduced viability was associated with increased Mt DNA damage, reduced Mt mass (manifested by reduced Mt protein expression and MitoTracker Green fluorescent labeling), and impaired Mt function (manifested by reduced levels of 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyltetrazolium bromide activity, cytochrome oxidase‐Complex IV, Subunit II expression, and MitoTracker Red fluorescence). The adverse effects of ethanol on Mt function were reduced by pretreating the cells with broad‐spectrum caspase inhibitors and nearly abolished by nerve growth factor stimulation, with or without concomitant treatment with global caspase inhibitors.Conclusions: These results suggest that ethanol‐induced death of insulin‐stimulated immature neuronal cells is mediated in part by impaired Mt function associated with Mt DNA damage and reduced Mt mass, and therefore it is likely to contribute to neuronal loss associated with fetal alcohol syndrome. The findings also suggest that the adverse effects of ethanol on insulin‐stimulated survival and metabolic function could be overcome by stimulating with growth factors that support Mt function through insulin‐independent pathways.
Relationship of Brain Ethanol Metabolism to the Hypnotic Effect of Ethanol. II: Studies in Selectively Bred Rats and Mice
Authors: Zimatkin Sergey M. , Liopo Anton V. , Satanovskaya Valentina I. , Bardina Lubov R. , Deitrich Richard A. 
Published: April 2006

Background : To clarify the role of brain acetaldehyde in the hypnotic effect of ethanol, we compared the ethanol‐oxidizing capacity (rate of acetaldehyde accumulation) and catalase and aldehyde dehydrogenase activity in the brains of animals genetically selected for different sensitivities to the hypnotic effect of ethanol.Methods: We used high, low, or control alcohol‐sensitive rats (HAS, LAS, and CAS) and short‐ and long‐sleep mice (SS and LS), as well as SS × LS recombinant inbred mice with known strain differences in mean duration of ethanol‐induced sleep. We studied the rate of accumulation of acetaldehyde from ethanol in brain homogenates of these animals and correlated those values with their hypnotic sensitivity to ethanol.Results: Acetaldehyde accumulation from ethanol was significantly higher in the brain homogenates from HAS rats and LS mice with high sensitivity to the hypnotic effect of ethanol in vivo, compared with LAS rats and SS mice with low sensitivity to ethanol. A correlation was found between the duration of ethanol‐induced sleep and the in vitro rate of accumulation of ethanol‐derived acetaldehyde in the brains of recombinant SS × LS mice strains. There was no correlation of sleep time with brain catalase levels. There were no line differences in brain catalase or aldehyde dehydrogenase or in alcohol or aldehyde dehydrogenase activity in livers of LAS, CAS, and HAS rats or in SS and LS mice.Conclusions: A correlation between the brain acetaldehyde accumulation, but not catalase levels, and the central effect of ethanol was demonstrated in animals genetically differing in initial sensitivity to the hypnotic effect of ethanol.
Fetal and Infantile Alcohol‐Mediated Associative Learning in the Rat
Authors: Abate Paula , Spear Norman E. , Molina Juan Carlos 
Published: April 2006

Background : Infant rats express conditioned responses to an odor experienced prenatally as a chemosensory cue associated with moderate alcohol intoxication. This study examined postnatal intake of a chemosensory cue (cineole) that had been paired with alcohol's unconditioned effects. It also tested the interaction between prenatal association and postnatal conditioning with cineole and alcohol.Methods: Pregnant female rats intubated with cineole were given ethanol (EtOH) .25 or 4.0 hr later. Other groups received only water or water paired with ethanol. During postnatal day 15 (PD15), infant consumption of cineole solution was assessed. After the cineole drinking test, pups were intubated with EtOH or water to assess infant conditioning. On PD16, all pups were tested for mouthing to milk alone or to a milk‐cineole solution.Results: Statistical analysis confirmed fetal associative conditioning attributable to the unconditioned effects of prenatal alcohol. Fetuses given explicit pairings of cineole and alcohol ingested less cineole on PD15 than control fetuses given a 4‐hr interval between cineole and alcohol.On PD16, consumption of cineole was significantly increased by prenatal exposure to cineole. Teratogenic effects of this dose of prenatal alcohol did not affect postnatal associative or nonassociative behavior.Conclusions: Prenatal associative learning can be established through temporal contiguity between fetal chemosensory stimulation and alcohol's unconditioned properties. This associative memory survives to infancy and modulates intake patterns and behavioral reactivity to substances that were prenatally paired with alcohol intoxication.
Chronic Daily Ethanol and Withdrawal: 2. Behavioral Changes During Prolonged Abstinence
Authors: Rasmussen Dennis D. , Mitton Dennis R. , Green Jillian , Puchalski Stephaney 
Published: April 2006

Background : Our previous investigations have suggested that alcohol abuse may induce persistently compromised hypothalamo‐pituitary‐adrenal (HPA) function, which could increase risk for subsequent alcohol abuse. The apparent similarity of chronic alcohol abuse–induced HPA defects to the compromised HPA functions associated with posttraumatic stress disorder and atypical depression also suggest potential common mechanisms shared with varied neurobehavioral disorders. Accordingly, we have investigated persistent behavioral effects of previous repetitive daily ethanol consumption and withdrawal.Methods: Male Sprague‐Dawley rats received either daily ad libitum chow, ad libitum liquid diet containing ethanol, or pair‐fed isocaloric control liquid diet. The ethanol was gradually introduced over 4 weeks, maintained at 5% w/v for four subsequent weeks, and then gradually removed over 1 week.Results: Four weeks after removal of ethanol from the diet, the previously ethanol‐consuming rats exhibited greater (p < 0.05) evidence of anxiety in the elevated plus‐maze test and in the novel cork‐gnawing test, as well as greater (p < 0.05) locomotor response to a novel environment, compared with controls.Conclusions: These results suggest that repetitive daily alcohol consumption and withdrawal can induce not only persistent defects in HPA function, but also persistent increases in anxiety and behavioral responsiveness to novelty, all consistent with characteristics of abstinent alcoholics as well as with rats that self‐administer increased amounts of alcohol and other drugs of abuse. This suggests that alcohol abuse can induce persistent common or interacting changes in neuroendocrine and behavioral responses that may increase risk for subsequent abuse.
Comparison of the Adaptive Functioning of Children Prenatally Exposed to Alcohol to a Nonexposed Clinical Sample
Authors: Whaley Shannon E. , O'Connor Mary J. , Gunderson Brent 
Published: April 2006

Background : Several studies show impairments in the social and adaptive behaviors of children prenatally exposed to alcohol. However, there remains limited consensus on whether the alcohol exposure directly affects social functioning or whether its effect is mediated by deficits in IQ. In addition, no studies have investigated whether deficits in social functioning are significantly more pronounced in children prenatally exposed to alcohol than in children referred to psychiatric treatment who were not prenatally exposed. We explored the effect of alcohol exposure on social and adaptive functioning and explored whether or not social and adaptive functioning are significantly more impaired in children prenatally exposed to alcohol than in a clinical sample of children.Methods: A sample of 33 alcohol‐exposed children was compared with a sample of 33 clinic‐referred nonexposed children. The groups were compared on measures of communication, daily living skills, and socialization. The groups were matched on sex, age, IQ, and outpatient or inpatient status.Results: Analyses revealed that the prenatally alcohol‐exposed children did not differ significantly from the nonexposed children in any of the domains of adaptive functioning. However, with age, exposed children showed a more rapid decline in socialization standard scores compared with the nonexposed clinical sample.Conclusions: Young children who were exposed to alcohol prenatally show deficits in all domains of adaptive functioning. Although these deficits do not seem to differ from those exhibited by young children with psychiatric problems but no prenatal exposure, deficits in socialization behavior of prenatally exposed children may become more significant with age.
Electroencephalogram Spectral Characteristics After Alcohol Ingestion in Japanese Men With Aldehyde Dehydrogenase‐2 Genetic Variations: Comparison With Peripheral Changes
Authors: Nishimura Fusae T. , Fukunaga Tatsushige , Nishijo Hisao , Ono Taketoshi , Kajiura Hideaki , Yokomukai Yoshiko 
Published: April 2006

Background : Electroencephalographic (EEG) activity induced by alcohol ingestion may be influenced by individual differences in alcohol metabolism. Specifically, an absence of the low Km isozyme of aldehyde dehydrogenase (ALDH), found in many Asians, may be related to alterations of EEGs.Methods: EEG power spectral changes induced by 0.4 ml/kg of alcohol ingestion were compared in two groups of Japanese subjects: NN (ALDH2*1/1, n= 19) and ND (ALDH2*2/1, n= 12). Peripheral changes in heart rate and facial skin temperature were evaluated after the same treatment. Blood ethanol, acetaldehyde, and catecholamine levels were determined to evaluate mediation of the ethanol metabolite, acetaldehyde, and its indirect action on EEGs through the effects on peripheral systems.Results: As expected, blood acetaldehyde was about 10‐fold higher in the ND subjects compared with the NN subjects during the postingestion period. Ethanol produced characteristic EEG changes during and after ingestion. The ND subjects, however, displayed brief periods of decrease in slow α immediately after alcohol ingestion and showed no long‐term EEG changes. The EEG changes were parallel to peripheral changes.Conclusions: The lack of increased EEG power in the ND subjects may be partly mediated by a direct action of the high concentration of acetaldehyde in the central nervous system that penetrates from the peripheral blood. In addition to this direct action of acetaldehyde, an indirect action, such as feedback from peripheral changes, might prevent the characteristic increase in α and β power observed in the NN subjects.
Effects of Alcohol Consumption on Indices of Iron Stores and of Iron Stores on Alcohol Intake Markers
Authors: Whitfield J. B. , Zhu G. , Heath A. C. , Powell L. W. , Martin N. G. 
Published: April 2006

Background : Alcohol increases body iron stores. Alcohol and iron may increase oxidative stress and the risk of alcohol‐related liver disease. The relationship between low or “safe” levels of alcohol use and indices of body iron stores, and the factors that affect the alcohol‐iron relationship, have not been fully characterized. Other aspects of the biological response to alcohol use have been reported to depend on iron status.Methods: We have measured serum iron, transferrin, and ferritin as indices of iron stores in 3375 adult twin subjects recruited through the Australian Twin Registry. Information on alcohol use and dependence and smoking was obtained from questionnaires and interviews.Results: Serum iron and ferritin increased progressively across classes of alcohol intake. The effects of beer consumption were greater than those of wine or spirits. Ferritin concentration was significantly higher in subjects who had ever been alcohol dependent. There was no evidence of interactions between HFE genotype or body mass index and alcohol. Alcohol intake–adjusted carbohydrate‐deficient transferrin was increased in women in the lowest quartile of ferritin results, whereas adjusted γ‐glutamyltransferase, aspartate aminotransferase, and alanine aminotransferase values were increased in subjects with high ferritin.Conclusions: Alcohol intake at low level increases ferritin and, by inference, body iron stores. This may be either beneficial or harmful, depending on circumstances. The response of biological markers of alcohol intake can be affected by body iron stores; this has implications for test sensitivity and specificity and for variation in biological responses to alcohol use.
Influence of Alcohol Intake on Risk for Increased Low‐Density Lipoprotein Cholesterol in Middle‐Aged Japanese Men
Authors: Nakanishi Noriyuki , Yoshida Hiroshi , Nakamura Koji , Kawashimo Haruhito , Tatara Kozo 
Published: April 2006

Background : Decreased low‐density lipoprotein (LDL) cholesterol in chronic alcoholics is well known. However, the importance of light to moderate alcohol consumption is less certain.Methods: We investigated the association of alcohol intake with risk for increased LDL cholesterol over 5 years in a cohort of 933 Japanese male office workers aged 35 to 54 years who had LDL cholesterol levels less than 140 mg/dl and were not taking medication for dyslipidemia, hypertension, diabetes, liver disease, or hyperuricemia at study entry. Incident‐increased LDL cholesterol was defined by an LDL cholesterol level of 140 mg/dl or more or use of medication for dyslipidemia. Each individual's slope for LDL cholesterol was also calculated with a simple linear regression model.Results: Three hundred twenty‐one men developed increased LDL cholesterol during 3785 person‐years of follow‐up. After controlling for potential predictors of increased LDL cholesterol, the relative risk for increased LDL cholesterol compared with nondrinkers was 0.89 for those who drank 0.1 to 22.9 g/day of ethanol, 0.74 for those who drank 23.0 to 45.9 g/day of ethanol, 0.64 for those who drank 46.0 to 59.9 g/day of ethanol, and 0.54 for those who drank 69.0 g/day or more of ethanol (p < 0.001). Slopes of LDL cholesterol level decreased significantly as alcohol intake increased. From multiple linear regression analyses, alcohol intake remained as an independent negative factor for slopes of LDL cholesterol level.Conclusions: Alcohol intake is negatively associated with development of increased LDL cholesterol in middle‐aged Japanese men.
Fetal and Maternal Sheep Hypothalamus Pituitary Adrenal Axis Responses to Chronic Binge Ethanol Exposure During the Third Trimester Equivalent
Authors: Cudd Timothy A. , Chen Wei‐Jung A. , West James R. 
Published: April 2006

Background : We tested the hypothesis that in utero ethanol exposure results in changes in fetal and maternal adrenocorticotropin (ACTH) and cortisol during the third trimester equivalent, by using a chronically instrumented fetal sheep model.Methods: Pregnant ewes received saline or ethanol intravenously 3 consecutive days per week from day 109 to day 132 of gestation. Fetal and maternal blood samples were collected on days 118 and 132.Results: Maternal and fetal ACTH and cortisol values increased on days 118 and 132 of gestation in response to ethanol infusions that created blood ethanol concentrations (BECs) that are easily achievable by human drinkers. Peak ACTH and cortisol values were detected 30 to 60 min after peak BECs were achieved.Conclusions: Chronic ethanol exposure during the third trimester equivalent in sheep resulted in repeated activation of the hypothalamus‐pituitary‐adrenal axis in both the mother and fetus. Temporally, the patterns of maternal and fetal responses to ethanol infusion were similar. We conclude that ovine maternal ethanol exposure during the third trimester equivalent increases fetal ACTH and cortisol concentrations, hormonal responses that may play a role in mediating alcohol‐related birth defects.
Direct Evidence for a Cause‐Effect Link Between Ethanol Potentiation of GABAA Receptor Function and Intoxication From Hyperbaric Studies in C57, LS, and SS Mice
Authors: Davies Daryl L. , Alkana Ronald L. 
Published: April 2006

Background: This article uses a direct ethanol antagonist, increased atmospheric pressure, to further test the causative link between ethanol potentiation of γ‐aminobutyric acid (GABA) type A receptor function and ethanol's behavioral effects. This was done by determining whether initial biochemical findings in long‐sleep (LS) mice extended to other genotypes and whether the previously reported insensitivity of short‐sleep (SS) mice to pressure antagonism of ethanol‐induced loss of righting reflex extended to a nonselected ethanol‐induced behavior.Methods: The effects of 12 times normal atmospheric pressure of helium‐oxygen gas (heliox) versus ethanol (25–200 mM) potentiation of GABA‐activated Cl− uptake in brain membranes (microsacs) from C57, LS, and SS mice were tested by using a 36Cl− flux assay. The effects of pressure versus ethanol's (2 g/kg) anticonvulsant effect in SS mice were tested by using time to onset of isoniazid‐induced myoclonic seizures.Results: Exposure to 12 times normal atmospheric pressure heliox antagonized ethanol potentiation of GABA‐activated Cl− uptake in all three genotypes across a range of ethanol concentrations that cause ethanol's behavioral and anesthetic effects. Pressure did not affect baseline receptor function. The threshold for initiating ethanol potentiation differed between genotypes in accordance with their behavioral sensitivities to ethanol (C57 and LS, ≤25 mM; SS, >50 mM). Pressure antagonized ethanol's anticonvulsant effect in SS mice.Conclusions: The results add important direct evidence supporting the hypothesis that ethanol potentiation of GABAA receptor function is an initial action of ethanol causing its behavioral effects. These findings also provide insight into possible effects of selective breeding on GABAA receptor function.