Biomedical subjects

C J Eriksson

Publications and source records attributed to C J Eriksson.

At least 19 recordsLinked to original sources

PubMed2001

Lack of effect of alcohol on ethinylestradiol in premenopausal women.

An acute elevation in estradiol during alcohol intake has been reported in postmenopausal women on estrogen replacement therapy. The objective of the present study was to investigate the acute and long-term effect of alcohol on ethinylestradiol, the estrogen component found in most oral contraceptives. Nine healthy premenopausal women with regular use of an oral contraceptive containing 30 microg ethinylestradiol and 75 microg gestodene were challenged with alcohol (0.4 g/kg p.o., approximately 2-3 standard drinks) 2 h after intake of the oral contraceptive pill at menstrual cycle day 14. Blood samples were taken at 0, 2, 3, 4, 5, and 6 h from intake of alcohol. The challenge was repeated after a 7-day period of controlled alcohol intake (0.8 g/kg/day) at cycle day 21. The same experiments were carried out during placebo conditions. At day 21 an increase in the alcohol elimination rate was observed compared with day 14. No significant acute or long-term effect of alcohol on ethinylestradiol was found. The lack of an acute effect comparable to that reported for estradiol may be due to the protection of the ethinyl group at the 17-position of ethinylestradiol.

Adult↗

PubMed2001

Alcohol intake, androgen and glucocorticoid steroids in premenopausal women using oral contraceptives: an interventional study.

Long-term heavy alcohol intake is associated with endocrinological abnormalities the mechanisms of which are still unclear. The objective of the present study was to investigate the effect of alcohol intake on plasma and urine glucocorticoid and androgen steroid levels in healthy premenopausal women using oral contraceptives. In a placebo-controlled interventional study with a cross-over design including nine premenopausal women using oral contraceptives no effect of tolerance was observed with regard to the magnitude of the acute transient alcohol-induced testosterone elevation after a 1-week alcohol drinking period (0.8 g/kg per day). At non-intoxicated time points elevated plasma testosterone and androstenedione levels were found in the afternoon but not in the morning during the alcohol drinking period compared with placebo. An increase in plasma cortisol levels was observed after the discontinuation of alcohol drinking. No effects were observed in total glucocorticoid conjugates in morning urine spot samples. An increase during the alcohol period relative to placebo was, however, observed in the urine etiocholanolone/androsterone, tetrahydrocortisol/allotetrahydrocortisol as well as the 20-hydroxy-/20-ketosteroid ratios. No consistent effect was observed in the urine (tetrahydrocortisol+allotetrahydrocortisol)/tetrahydrocortisone ratio. It is suggested that the alcohol-induced alterations in plasma glucocorticoid and androgen levels during non-intoxicated conditions are due to a change in the hypothalamic-pituitary-adrenal function. The effects observed in the conjugated urine glucocorticoid and androgen ratios are likely to be mediated by a change in the metabolism of these steroids in the liver. The present results may be of relevance in the development of disturbances in the glucocorticoid as well as sex steroid balance among heavy female drinkers.

Adult↗

PubMed2001

The role of acetaldehyde in the actions of alcohol (update 2000).

BACKGROUND: Recent advances in the field of acetaldehyde (AcH) research have raised the need for a comprehensive review on the role of AcH in the actions of alcohol. This update is an attempt to summarize the available AcH research. METHODS: The descriptive part of this article covers not only recent research but also the development of the field. Special emphasis is placed on mechanistic analyses, new hypotheses, and conclusions. RESULTS: Elevated AcH during alcohol intoxication causes alcohol sensitivity, which involves vasodilation associated with increased skin temperature, subjective feelings of hotness and facial flushing, increased heart and respiration rate, lowered blood pressure, sensation of dry mouth or throat associated with bronchoconstriction and allergy reactions, nausea and headache, and also reinforcing reactions like euphoria. These effects seem to involve catecholamine, opiate peptide, prostaglandin, histamine, and/or kinin mechanisms. The contribution of AcH to the pathological consequences of chronic alcohol intake is well established for different forms of cancer in the digestive tract and the upper airways. AcH seems to play a role in the etiology of liver cirrhosis. AcH may have a role in other pathological developments, which include brain damage, cardiomyopathy, pancreatitis, and fetal alcohol syndrome. AcH creates both unpleasant aversive reactions that protect against excessive alcohol drinking and euphoric sensations that may reinforce alcohol drinking. The protective effect of AcH may be used in future treatments that involve gene therapy with or without liver transplantation. CONCLUSIONS: AcH plays a role in most of the actions of alcohol. The individual variability in these AcH-mediated actions will depend on the genetic polymorphism, not only for the alcohol and AcH-metabolizing enzymes but also for the target sites for AcH actions. The subtle balance between aversive and reinforcing, protecting and promoting factors will determine the overall behavioral and pathological developments.

Acetaldehyde↗

PubMed2001

Functional relevance of human adh polymorphism.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were C. J. Peter Eriksson and Tatsushige Fukunaga. The presentations were (1) 4-Methylpyrazole as a tool in the investigation of the role of ADH in the actions of alcohol in humans, by Taisto Sarkola and C. J. Peter Eriksson; (2) ADH2 polymorphism and flushing in Asian populations, by Wei J. Chen, C. C. Chen, J. M. Ju, and Andrew T. A. Cheng; (3) Role of ADH3 genotypes in the acute effects of alcohol in a Finnish population, by Hidetaka Yamamoto, Kathrin Kohlenberg-Müller, and C. J. Peter Eriksson; (4) Clinical characteristics and disease course of alcoholics with different ADH2 genotypes, by Mitsuru Kimura, Masanobu Murayama, Sachio Matsushita, Haruo Kashima, and Susumu Higuchi; (5) ADH2 polymorphism, alcohol drinking, and birth defects, by Lucinda Carr, D. Viljoen, L. Brooke, T. Stewart, T. Foroud, J. Su, and Ting-Kai Li; and (6) ADH genotypes and alcohol use in Europeans, by John B. Whitfield.

Adult↗

PubMed2001

The role of the liver in the acute effect of alcohol on androgens in women.

The hypothalamic-pituitary-gonadal and -adrenal axes are regarded as the main sites of the actions of alcohol on steroids. In the present study the effect of alcohol (0.4-0.5 g/kg, orally) on venous plasma and urinary androgens was investigated in 21 premenopausal women using oral contraceptives as well as in 10 premenopausal nonusers. After intake of alcohol, an acute elevation in plasma testosterone, a decline in androstenedione levels, and an elevation in the ratio of testosterone to androstenedione were observed in both groups. The effects lasted throughout the period of ethanol elimination and were abolished during pretreatment with 4-methylpyrazole (10-15 mg/kg, orally). The acute effects were higher in the group using oral contraceptives than in the nonusers. The testosterone effect in plasma was reflected in the free testosterone fraction. A decline in urinary androsterone and etiocholanolone levels, the principal catabolic products of androgens, was observed during alcohol intoxication. In conclusion, the present acute effects on plasma and urinary steroid hormones seem to be explained by an inhibited catabolism mediated by the alcohol-induced change in the redox state in the liver. Our results suggests that the liver should be included as a major site in the acute endocrinological effects of alcohol on steroid hormones in women.

Adult↗

PubMed2001

Effect of 4-methylpyrazole on endogenous plasma ethanol and methanol levels in humans.

BACKGROUND: Endogenous methanol and ethanol levels are found in human blood. It is assumed that these compounds are derived mainly from microflora in the gastrointestinal tract and that the small amounts formed are consequently eliminated, mainly in the liver, by the alcohol dehydrogenase (ADH) pathway. The objective of the present study was to investigate the effect of 4-methylpyrazole (4-MP), a specific ADH inhibitor, on endogenous plasma methanol and ethanol levels in healthy women and men. METHODS: A double-blind placebo-controlled interventional study was carried out. RESULTS: A significant elevation in plasma endogenous ethanol and methanol levels was observed after intake of 4-MP (10-15 mg/kg p.o.). For methanol levels, a linear increase from 20 +/- 14 micromol/l before intake to 39 +/- 22 micromol/l at 420 min from intake of 4-MP (levels 20 +/- 14 micromol/l and 14 +/- 9 micromol/l during the corresponding placebo time points) was found. For ethanol, concentrations increased from levels below detection limit (i.e., < 5 micromol/l, determined by headspace gas chromatography) before intake to 30 +/- 20 micromol/l at 195 min from intake of 4-MP. A small increase in ethanol levels, to 13 +/- 8 micromol/l, but not in methanol levels, was observed after the intake of lingonberry juice containing no ethanol or methanol. No sex differences in the ethanol and methanol levels before or after the intake of 4-MP were found. CONCLUSIONS: The present study provides conclusive evidence for a constant endogenous production as well as clearance of ethanol and methanol in humans. In addition, the study shows that the ethanol and methanol produced are, at least in part, eliminated by the ADH pathway.

Adult↗

PubMed2000

Mean cell volume and gamma-glutamyl transferase are superior to carbohydrate-deficient transferrin and hemoglobin-acetaldehyde adducts in the follow-up of pregnant women with alcohol abuse.

BACKGROUND AND OBJECTIVE: To compare the usefulness of carbohydrate-deficient transferrin (CDT), the ratio of CDT to total transferrin, and hemoglobin-acetaldehyde adducts with mean cell volume (MCV) and gamma-glutamyl transferase (GGT) in the follow-up of alcohol abuse during pregnancy. METHODS: Forty-four pregnant drug and alcohol abusing female patients attending a special outpatient clinic were followed from the 8th to 24th gestational week onwards. A population of sixty-two healthy pregnant women was recruited to assess the effect of gestation on the markers. RESULTS: Eight of thirteen heavy drinking (> or =8 drinks/week) patients delivered infants with fetal alcohol effects (FAE). MCV and GGT were higher among heavy drinking patients than in moderately drinking (<8 drinks/week) patients (92+/-4 vs 90+/-3 fl and 31+/-34 vs 16+/-10 U/ L, respectively), and in patients delivering infants with FAE compared with patients delivering healthy infants (95+/-3 vs 90+/-3 fl and 34+/-26 vs 15+/-10 U/L, respectively). Hemoglobin-acetaldehyde adducts, CDT, and the ratio of CDT to total transferrin were neither associated with the reported level of alcohol consumption nor with the occurrence of FAE. In the receiver operating characteristics analysis MCV was found to be superior to CDT and the adducts, and GGT superior to the adducts, in identifying heavy drinking and in predicting FAE. In the control population, both CDT and total transferrin were found to rise during pregnancy, whereas the ratio of CDT to total transferrin was found to decline. The upper reference range of 33 U/L for CDT was considerably higher than that of non-pregnant women (26 U/L). CONCLUSION: MCV and GGT appear to be the most efficient laboratory markers for detecting excessive alcohol consumption and the adverse effects of alcohol on the fetus.

Acetaldehyde↗

PubMed2000

Platelet adenylyl cyclase activity as a trait marker of alcohol dependence. WHO/ISBRA Collaborative Study Investigators. International Society for Biomedical Research on Alcoholism.

BACKGROUND: There is compelling evidence that genetic factors play a major role in the development of alcohol dependence. Platelet adenylyl cyclase (AC) activity has been proposed as a biochemical marker for differentiating alcohol-dependent and nondependent subjects, but the sensitivity and specificity of this marker have not been ascertained. The objective of this study was to determine the sensitivity and specificity of platelet AC activity in identifying alcohol-dependent subjects and to ascertain the effect of medical/ psychiatric variables, drinking and smoking history, and age and body weight on AC activity. METHODS: The cross-sectional study was conducted from 1995 to 1998. Participants were 210 Australian White men who were community volunteers and alcohol treatment inpatients in Sydney, Australia. There were 41 nondrinkers, 140 drinkers, and 29 men who were entering alcohol treatment. The main outcome measure was platelet AC activity. Classification variables were plasma ethanol, gamma-glutamyltransferase, aspartate aminotransferase, serum carbohydrate-deficient transferrin (CDT), and urinary 5-hydroxytryptophol/5-hydroxyindoleacetic acid (5-HTOL/5-HIAA) levels, and World Health Organization/International Society for Biomedical Research on Alcoholism Interview Schedule variables, which included alcohol use and dependence criteria. RESULTS: Among subjects who reported abstinence for at least 4 days, both cesium fluoride (CsF)- and forskolin-stimulated platelet AC activities were significantly lower in those with a lifetime history of alcohol dependence compared with those with no such history (p < 0.005 and p < 0.05, respectively). The sensitivity and specificity of CsF-stimulated AC activity to discriminate individuals with a lifetime history of alcohol dependence were 75% and 79%, respectively. Similar values for sensitivity and specificity for CsF-stimulated AC activity were calculated when discriminating current alcohol dependence in the subjects in our sample. Irrespective of the history of alcohol dependence, persons who had consumed alcohol recently (within the last 3-4 days) showed significantly higher mean basal, CsF-stimulated, and forskolin-stimulated AC activity (p < 0.001), as did those who had elevated 5-HTOL/5-HIAA ratios or CDT levels, indicative of recent (heavy) drinking. The "normalization" of platelet AC activity to baseline levels after an individual stops drinking may be related to the generation of new platelets during the abstinence period. Conduct disorder and antisocial personality disorder were not associated with low AC activity, but low forskolin-stimulated AC activity was associated with major depression. CONCLUSIONS: We found that CsF- and forskolin-stimulated platelet AC activity discriminates between subjects with and without alcohol dependence in a population of subjects who had not consumed significant quantities of ethanol recently. Recent alcohol consumption is a confounding variable that can alter the measured levels of AC activity. Forskolin-stimulated platelet AC activity also may be influenced by a history of major depression.

Adenylyl Cyclases↗

PubMed1999

Effects of continuous versus intermittent ethanol exposure on rat sympathetic neurons.

BACKGROUND: Binge ethanol exposure is known to induce degeneration of central nervous system (CNS) neurons. Sympathetic hyperactivity has been related to ethanol withdrawal symptoms, but the effects of repeated withdrawals on peripheral sympathetic neurons have not been studied previously. METHODS: The effects of continuous versus intermittent ethanol consumption on sympathetic neurons of the superior cervical ganglion (SCG) were studied in male Wistar rats. Two-month-old rats were divided into three groups: one group with ethanol (10% v/v) as the drinking fluid throughout the 51/2-month experiment (continuous, n = 9), one group drinking ethanol on 4 days/week and water on 3 days/week (intermittent, n = 9), and a control group (n = 9) with water as the only available fluid. All groups had food ad libitum. SCG volume, neuron density, and total number of neurons were measured by using unbiased morphometric methods. RESULTS: As the mean daily ethanol consumption did not differ between the two ethanol-exposed groups (continuous 5.7 g/kg/day versus intermittent 5.8 g/kg/day), the total dose of ethanol consumed was 42% smaller in the intermittent group. The total number of SCG neurons decreased by 28%, and neuron density by 23%, in the intermittent group compared with the control group, whereas no significant neuron loss was observed in the continuous group. The volume of the SCG was similar in all study groups. The results suggest that repeated ethanol withdrawals, rather than ethanol exposure per se, are deleterious to sympathetic neurons. CONCLUSIONS: Ethanol-induced degeneration of neurons is not only related to the amount of ethanol consumed, but also to the patterns of drinking.

Adrenergic Fibers↗

PubMed1999

Drinking, menstrual cycle, and female sexuality: a diary study.

Sexual feelings in connection with alcohol intake were investigated in 97 Finnish women aged 18 to 35 years. The subjects were drawn from a population sample and included both oral contraceptive users and nonusers. Structured diaries were used to monitor sexual feelings and alcohol intake during one menstrual cycle for each subject. Alcohol drinking was found to be significantly associated with elevated sexual interest and arousal in the post- and intermenstrual phases. We suggest that these phase-dependent effects could be due to known alcohol-mediated testosterone elevations.

Adolescent↗

PubMed1999

Acute effect of alcohol on estradiol, estrone, progesterone, prolactin, cortisol, and luteinizing hormone in premenopausal women.

BACKGROUND: Heavy alcohol consumption is associated with menstrual irregularities, including anovulation, luteal-phase dysfunction, recurrent amenorrhea, and early menopause. In addition, moderate to heavy alcohol intake has been found to increase the risk of spontaneous abortions and breast cancer. These adverse effects could at least in part originate from alcohol-mediated changes in hormone levels. METHODS: The acute effect of alcohol on the hormone balance in women using oral contraceptives (OC+) and also in nonusers (OC-), was evaluated in 30 OC- and 31 OC+ subjects, representing the whole period of the menstrual cycle. It was also evaluated in 40 OC- and 47 OC+ subjects during the midcycle phase and in 10 OC+ subjects with unknown cycle phase. RESULTS: We found that among subjects who used oral contraceptives, estradiol levels increased and progesterone levels decreased after intake of alcohol (0.5 g/kg). No dose effect (0.34-1.02 g/kg) on progesterone was observed in a substudy on 10 OC+ subjects. With regard to estrone levels, no effect was observed, although a significant increase was found in the estradiol-to-estrone ratio. Among subjects not using oral contraceptives, progesterone levels decreased after intake of alcohol (0.5 g/kg). No effect was found in estradiol, estrone, or the estradiol-to-estrone ratio during midcycle in this study group. A transient elevating effect of alcohol (0.5 g/kg) on prolactin levels was observed in both study groups. We found that alcohol (0.5 g/kg) had no significant effect on luteinizing hormone (LH) levels among subjects not using oral contraceptives, and observed a decline among subjects using oral contraceptives at midcycle. CONCLUSIONS: We suggest that the estradiol and progesterone effects are related to decreased steroid catabolism, resulting from the alcohol-mediated increase in the hepatic NADH-to-NAD ratio. The transient effect on prolactin levels may reflect acute changes in opioid and dopamine levels in the hypothalamus. The present findings regarding female sex steroids may be of relevance in the association between moderate to heavy alcohol consumption and the development of breast cancer.

Adult↗

PubMed1998

Effects of naltrexone and ethanol on auditory event-related brain potentials.

Acute effects of ethanol (0.55 g/kg) and the opioid antagonist naltrexone (50 mg) on auditory event-related brain potentials (ERP) (i.e., electrical brain activity time-locked to sensory stimuli) were investigated in 13 healthy social drinkers, using a double-blind, placebo-controlled, design. The subjects' task was to attend to tones presented to a designated ear while ignoring tones to the other, and to detect deviant tones among the attended tones. When administered alone, naltrexone significantly reduced the amplitude of the later part of negative difference (Nd[l]), suggesting impaired selective attention. However, this effect might have been caused by naltrexone-induced nausea. Ethanol, when ingested alone, attenuated the amplitude of the N1, and increased the peak latencies of the mismatch negativity (MMN) and N2b that have been suggested to reflect automatic change detection in audition and allocation of attentional resources to processing of stimulus deviance, respectively. In contrast, the P1 amplitude was augmented by alcohol, but only when the tones were attended. When ethanol and naltrexone were simultaneously ingested, however, the alcohol-induced P1 amplitude augmentation was canceled, thus tentatively suggesting opioidergic mediation of this alcohol effect. In contrast, the MMN peak latency was increased significantly more in the interaction condition than in the ethanol condition, thus suggesting that the detrimental effects of alcohol on involuntary attention switching were augmented by naltrexone. Furthermore, the N2b amplitude was significantly suppressed in the interaction condition, suggesting attentional impairment.

Adult↗

PubMed1997

Voluntary alcohol drinking and acetaldehyde metabolism in F2 hybrid crosses of AA and ANA rat lines.

Alcohol-preferring AA and alcohol-avoiding ANA rat lines differ in their acetaldehyde metabolism and this has been suggested to be one reason for their different ethanol drinking behavior. To study whether acetaldehyde accumulation is indeed associated with alcohol drinking behavior and to evaluate which enzymatic differences previously observed in these rat lines are of importance in this regard, we produced an F2 generation from them. ADH and ALDH activities, and ALDH patterns were then assessed from these hybrids and correlated with their voluntary ethanol drinking and blood acetaldehyde concentrations measured during ethanol metabolism. A significant negative correlation between voluntary ethanol intake and blood acetaldehyde concentration was observed in F2 females drinking less than 17% of the total fluid as ethanol. In F2 males, hepatic microsomal high Km ALDH activities correlated negatively with blood acetaldehyde concentrations, indicating that low activity of this isoenzyme in ANA rats could be at least in part responsible for the accumulation of acetaldehyde in their blood. Finally, F2 rats that possessed the cytosolic ALDH isoenzyme pattern most frequently found in the AA rat line drank significantly more ethanol than the animals with typical ANA pattern, suggesting that this polymorphism might also be relevant in the regulation of voluntary ethanol drinking although it is probably not associated with acetaldehyde metabolism.

Acetaldehyde↗

PubMed1997

Effects of lifelong ethanol consumption on cerebellar layer volumes in AA and ANA rats.

Aging and chronic alcohol consumption can cause degenerative changes in the cerebellar cortex. In this study, the effects of aging and lifelong alcohol consumption on cerebellar cortical layer volumes (molecular and granular) and also white matter layer volumes were studied in alcohol-preferring (AA) and nonpreferring (ANA) rats of both sexes. The ethanol-consuming animals (EtOH) had 12% (w/v) ethanol as the only available fluid from 4 to 22 months of age, whereas the young (3 month) and old controls (24 months) had only water to drink. The volumes of molecular, granular, and white matter layers of the cerebellar vermis in folia II, IV, VII, and X were measured by using systematic sampling and a point-counting method. The volumes of the granular and white matter layers showed consistent increase between 3 and 24 months of age, whereas the volume of the molecular layer remained unchanged with increasing age. Individual ethanol intake was measured over a 1-week period at the beginning and at the end of chronic ethanol exposure. Significant (ANOVA, p = 0.000) sex difference was found in the drinking behavior in both lines, with females consuming more alcohol than males (daily ethanol consumption at 22 months of age 3.2 +/- 0.3 vs. 7.1 +/- 0.3 g/kg for AA males and females; 3.2 +/- 0.3 vs. 5.4 +/- 0.4 g/kg for ANA males and females, respectively). The only ethanol-induced effect on the cerebellum was observed in ANA-EtOH females with a 15% reduction in the volumes of the molecular and granular layer in folium II compared with age-matched controls and a significant (p < 0.05, analysis of covariance with ethanol intake as a covariate) line difference in folium II (molecular and granular layers) was observed between ANA-EtOH females and AA-EtOH females. Furthermore, the volume of the molecular layer in folium II was significantly (p < 0.05, analysis of covariance with ethanol intake and body weights as covariates) reduced for ANA-EtOH females, compared with ANA-EtOH males indicating a sex difference in the cerebellar degeneration due to chronic alcohol consumption. Of the three layers studied, the white matter layer was the most resistant layer to the effects caused by chronic alcohol consumption. In view of the fact that AA and ANA rats of both sexes differ regarding the drinking behavior and ethanol metabolism, they provide an important model for further research on ethanol-induced pathological changes in the central nervous system.

Acetaldehyde↗

PubMed1997

Behavioral sensitivity and ethanol potentiation of the N-methyl-D-aspartate receptor antagonist MK-801 in a rat line selected for high ethanol sensitivity.

The role of the N-methyl-D-aspartate (NMDA) receptors in differential ethanol sensitivity of the alcohol-insensitive [alcohol-tolerant (AT)] and alcohol-sensitive [alcohol-nontolerant (ANT)] rat lines selected for low and high sensitivity to ethanol-induced (2 g/kg) motor impairment was studied in behavioral and neurochemical experiments. A noncompetitive antagonist of the NMDA receptor, dizocilpine maleate (MK-801; 0.2 mg/kg), impaired motor function in ANT rats, but not in AT rats, in a tilting plane test. The impairment was further potentiated by a dose (0.75 g/kg) of ethanol, which alone was inactive. This effect was apparently not associated with the locomotor stimulation produced by MK-801 (0.1 and 0.2 mg/kg), because stimulation did not differ between the rat lines. Locomotor stimulation was potentiated by the low ethanol dose in both rat lines. Ethanol treatment decreased the cerebellar and hippocampal cGMP concentrations both with and without MK-801 pretreatment in both rat lines. In situ hybridization using oligonucleotide probes specific for NMDA receptor subunit mRNAs NR1 and NR2A, B, C, and D revealed no clear differences in brain regional expression between ANT and AT rates. These results indicate that the alcohol-sensitive ANT rats are very sensitive to a low dose of ethanol in the presence of NMDA receptor antagonism, consistent with the hypothesis that this receptor system is involved in acute ethanol intoxication.

Alcoholism↗

PubMed1997

Manipulation of alcohol drinking by liver transplantation.

The procedure of liver transplantation in alcoholic liver disease raises the question whether it would be possible to regulate the recipient's future drinking by the choice of donor liver. To address this question, we conducted transplantations with rat lines selected for high (AA) and low (ANA) alcohol preference. AA recipients having alcohol experience before the operation remained heavy drinkers regardless of whether the graft came from an AA or ANA donor. However, in these AA recipients who started drinking only after the operation, differences emerged, with AA grafts creating heavy drinking and ANA donor livers resulting in very low drinking. An overall increase in the acetaldehyde levels was introduced by the ANA livers, thus reflecting the original line differences. Similarly, in subsequent experiments, it was observed that when the aldehyde dehydrogenase inhibitor calcium carbimide was introduced in different amounts to the diet, alcohol drinking was reduced more in animals not used to drinking. The magnitude of this effect, especially in situations with established heavy drinking, is of relevance in future contemplations about liver transplantations between humans with different aldehyde dehydrogenase genotypes.

Acetaldehyde↗

PubMed1996

Estrogen-related acetaldehyde elevation in women during alcohol intoxication.

Alcohol is more often unpleasant and causes tissue damage more rapidly in women than men. The present study was designed to find out whether acetaldehyde, the primary metabolite of alcohol, could play a crucial role in these actions. Special emphasis was focused on the appropriate determination of blood acetaldehyde and hormonal factors. Occurrence of elevated blood acetaldehyde levels during alcohol oxidation was established in both normally cycling women and ones taking oral contraceptives, but not in men. An association between elevated acetaldehyde levels and high estrogen phases was observed in both groups of women. Estrogen-related acetaldehyde elevation is suggested to be the key factor explaining the gender differences of the adverse effects of alcohol.

Acetaldehyde↗

PubMed1995

Consequence of long-term exposure to corticosterone or dexamethasone on ethanol consumption in the adrenalectomized rat, and the effect of type I and type II corticosteroid receptor antagonists.

The daily fluid intake of male Wistar rats with simultaneous access to 6% ethanol and water was determined during a baseline period (1 week), following adrenalectomy (1 week) and for 3 weeks following SC implantation of hormone pellets containing corticosterone (CORT) or dexamethasone (DEX). Ethanol consumption dropped during the first week of adrenalectomy (ADX) but increased again in the absence of hormone replacement to reach preoperative levels during the ensuing weeks. The CORT treatment, which produced plasma hormone levels similar to the 24-h mean concentration of adrenally intact rats, not only reversed the effect of ADX on alcohol consumption but also enhanced it to levels above those observed in intact rats. Water intake was not affected by the CORT treatment. DEX implants stimulated water intake, but did not enhance the drinking of ethanol. SC injections of RU 28318 (type I corticosterone receptor antagonist; 10 mg/kg) or mifepristone (RU 38486; type II receptor antagonist; 25 mg/kg) at the beginning and halfway through three daily, 6-h tests failed to affect ethanol drinking in adrenally intact rats or in ADX rats bearing CORT implants. Similarly, there was no effect of giving the two antagonists in combination. These results suggest that exogenous CORT can induce excessive alcohol intake in genetically unselected rats and that this facilitatory effect may be mediated by non-genomic cellular mechanisms.

Adrenalectomy↗