bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Liver Transplantation on the Hypothalamic‐Pituitary‐Gonadal Axis of Chronic Alcoholic Men with Advanced Liver Disease
Authors: Van Thiel D. H. , Kumar S. , Gavaler J. S. , Tarter R. E.
Published: April 2006

The hormones testosterone, follicle stimulating hormone (FSH), and luteinizing hormone (LH) were assayed in blood obtained from men with alcoholic liver disease before and after successful liver transplantation. The frequency and severity of self reported impotence, intercourse, and paternity were assessed before and 18 ± 3 months post‐transplantation. The results obtained were compared with those of age‐matched males transplanted within the same month by the same surgical teams for advanced hepatocellular disease other than alcoholism. Little change for any parameter assessed pre‐ and post‐transplantation was noted for the nonalcoholics. In contrast, the FSH, LH, and testosterone levels of the alcoholic men all increased significantly following successful transplantation. These data suggest that the liver disease associated with alcoholism contributes to some of the endocrine effects of alcohol‐associated cirrhosis but not all. Because the transplanted alcoholics remain less adequate than controls, it is further suggested that some residual alcohol‐induced injury to the hypothalamic‐pituitary‐gonadal axis persists despite successful liver transplantation.
Plasma Noradrenaline, Platelet α2‐Adrenoceptors, and Functional Scores during Ethanol Withdrawal
Authors: Smith A. J. , Brent P. J. , Henry D. A. , Foy A.
Published: April 2006

Plasma noradrenaline and platelet α2‐adrenoceptor density (sites/cell using 3H‐rauwolscine with and without phentolamine) were correlated with withdrawal score in 23 hospitalized patients undergoing ethanol withdrawal. Control groups for plasma noradrenaline were 25 patients admitted to hospital for elective gastroscopy and 12 laboratory workers accustomed to venipuncture. Controls for platelet α2‐adrenoceptor measurements were a separate group of 31 normal subjects with a mean age close to that of the patients' withdrawing from ethanol.

Plasma noradrenaline was significantly higher in the patients undergoing ethanol withdrawal than in patients admitted to hospital for elective endoscopy. Twelve laboratory controls had plasma noradrenaline levels significantly lower than either patient group.

A significant though poor statistical correlation existed between ethanol withdrawal score and simultaneously determined plasma noradrenaline level.

Platelet α2‐adrenoceptor sites/cell were reduced in ethanol withdrawal compared with the normal controls. Platelet α2‐adrenoceptor sites/cell increased over the first 24 hr of ethanol withdrawal but remained significantly lower than control values. The change in platelet adrenoceptors was accompanied by a fall in mean plasma noradrenaline.

Thus, the stress of hospital admission itself is associated with an increase in plasma noradrenaline, but ethanol withdrawal enhances this increase, which is accompanied by and probably causes a reduction in platelet α2‐adrenoceptor numbers. These changes begin to return towards normal within 24 hr as the withdrawal reaction subsides.
Development of Tolerance to Ethanol in Cultured Adrenal Chromaffin Cells
Authors: Harper J. C. , Littleton J. M.
Published: April 2006

Dissociated bovine adrenal chromaffin cells in culture were utilized to study the mechanisms for development of cellular tolerance to ethanol. Three days after plating, cells were grown in either control medium or medium containing 200 mm ethanol for periods up to 6 days. Catecholamine release induced by carbachol, 80 mm K+, BAY K 8644, and veratrine was studied in ethanol‐treated and untreated cultures. The presence of ethanol in vitro was inhibitory to all these stimuli in untreated cell cultures, carbachol‐induced release being most sensitive (IC50 approximately 30 mm). After growth in ethanol for 6 days, carbachol‐induced catecholamine release was completely resistant to the inhibitory effects of ethanol. The resistance to ethanol of carbachol‐induced catecholamine release from cells grown in medium containing ethanol also extended to the inhibitory effects of butanol. The results show some similarities with changes observed in the central nervous system during the development of ethanol tolerance, and it is suggested that this model system may be useful in examining the mechanisms by which tolerance occurs.
Application of the Tridimensional Personality Questionnaire to a Population of Alcoholics and Other Substance Abusers
Authors: Nixon Sara Jo , Parsons Oscar A.
Published: April 2006

To assess its construct validity and application, Cloninger's Tridimensional Personality Questionnaire (TPQ) was administered to 267 inpatient substance abusers. One hundred seventy‐two of the patients were alcoholic, 47 abused stimulants, and 48 abused other drugs, primarily benzodiazepines, marijuana, or were polysubstance abusers. Of the sample 33.8% were female. Analyses were conducted to (1) determine whether TPQ scores could be used to classify alcoholics as either Cloninger Type I or Type II; (2) examine the intercorrelations of TPQ scales and identify differences in these patterns due to drug of choice; (3) replicate previously obtained gender differences on the TPQ. The results indicate that (1) TPQ scores did not classify the alcoholics into the expected frequencies for Type I and Type II; (2) the scales were not independent and did not give rise to any differences among drug user groups, but (3) did confirm previously reported gender differences. These results indicate that Cloninger's model and the TPQ must be subjected to careful empirical study prior to their widespread acceptance.
Learned Tolerance to Alcohol: Mental Rehearsal with Imagined Consequences
Authors: Zinatelli Marna , Vogel‐Sprott Muriel
Published: April 2006

Two experiments tested the hypothesis that the acquisition of a new response is enhanced by mental rehearsal which includes the imagined consequence of mental performance. A total of 48 males participated in the research. Experiment 1 tested drug‐free learning of a motor skill task. Experiment 2 used the same task to test the acquisition of a drug‐compensatory response (i.e., tolerance) under alcohol. Subjects in each experiment were randomly assigned to one of three treatments: mental rehearsal with imagined consequences (C), mental rehearsal with no imagined consequences (N), and rest (R). Both experiments confirmed the hypothesis. C treatment yielded superior drug‐free performance, and a greater tolerance. The effect of N treatment was intermediate, and R treatment was least effective. It was concluded that incorporating an imagined consequence of mental performance enhances the learning of alcohol tolerance and the acquisition of a motor skill. Factors that may have contributed to the marginal efficacy of N treatment were discussed, and research implications were considered.
Ethanol Has Direct Inhibitory Effects on Steroidogenesis in Human Granulosa Cells: Specific Inhibition of LH Action
Authors: Saxena Sandhya , Meehan Daniel , Coney Ponjola , Wimalasena Jayantha
Published: April 2006

We have evaluated the direct effects of ethanol (EtOH) on the production of progesterone (P) and estradiol‐17β (E2) by cultured human granulosa cells obtained during in vitro fertilization procedures. On day 3 of culture, cells were divided into control and ethanol (20 mm) groups and stimulated by hFSH (50 ng/ml), hlh (0–50 ng/ml), FSH+LH, 8 Br‐cAMP (0.25 mm) and androstenedione (10−7 M). Experiments were terminated on days 7 and 9 and DNA, P, and E2 were measured. Ethanol inhibited P and E2 secretion stimulated by LH; however, there was no significant effect of ethanol on P and E2 production in the control group or when the cells were stimulated by FSH or cAMP. EtOH also had no effect on androstenedione stimulated E2 production. There was no significant difference in the DNA contents of the human granulosa cells in the ethanol group as compared with the control group. These results are the first demonstration of a direct effect of ethanol on cultured granulosa‐lutein cells and suggest that ethanol may inhibit action of LH on the corpus luteum. A direct selective toxic effect of EtOH on the ovary may be responsible for some of the reproductive abnormalities observed in alcoholic women.
Isoenzymes of Aldehyde Dehydrogenase in Human Lymphocytes
Authors: Dyck Lillian E.
Published: April 2006

The types of isozymes of aldehyde dehydrogenase (ALDH) present in human lymphocytes has been investigated using isoelectric focusing of polyacrylamide gels followed by substrate‐specific staining. Lymphocytes obtained from most individuals were found to contain both types I and II ALDH. This group of ‘typical’ individuals reported that they did not develop marked facial flushing or rapid heart rate after drinking alcohol nor did they develop an erythema to cutaneously applied ethanol. Lymphocytes obtained from ‘atypical’ individuals who do suffer from alcohol‐induced flushing and rapid heart rate and who developed erythema to cutaneous ethanol displayed type II, but not type I, ALDH. Lymphocytes thus appear to be an easily accessible and suitable tissue for determining type I ALDH phenotype.
Alterations in Splanchnic Blood Flow Following Chronic Ethanol Exposure
Authors: Piano Mariann R. , Ferguson J. L. , Melchior Christine L.
Published: April 2006

The purpose of these experiments was to determine whether or not tolerance develops to the effect of 3.0 g/kg ethanol on total and regional splanchnic blood flow in male Wistar rats. The animals were given the Lieber‐DeCarli liquid diet containing ethanol for 10 days; ethanol‐fed animals were withdrawn 24 hr prior to experiments. Regional blood flow and cardiac output (CO) were measured by the reference microsphere technique after an intraperitoneal injection of 3.0 g/kg of ethanol. Acute ethanol administration produced early nonsustained increases in portal vein blood flow in animals fed ethanol for 10 days and withdrawn for 24 hr and in control animals. However, after chronic exposure to ethanol, the pattern of increase in blood flow in response to ethanol in the splanchnic organs was different between the ethanol‐fed and control groups. Increases in portal vein flow in control groups were due to concomitant increases in small intestinal, colonic, and cecal blood flow while the increase in the ethanol‐fed group was due to a rise in small intestinal and stomach blood flow. The increase in stomach blood flow that occurred in the animals treated chronically with ethanol may be viewed as a conditioned response to ethanol, since this was not found in the control group. These results, demonstrate that the pattern of increase in blood flow in the splanchnic organs produced by an acute dose of ethanol depends on the animal's previous exposure to ethanol.
Moderate Prenatal Alcohol Exposure: Effects on Child IQ and Learning Problems at Age 7 1/2 Years
Authors: Streissguth Ann P. , Barr Helen M. , Sampson Paul D.
Published: April 2006

This longitudinal, prospective, population‐based study examined the long‐term effects of moderate prenatal alcohol exposure on 482 school aged children. Maternal reports of alcohol use obtained during pregnancy were significantly related to child IQ, achievement test scores, and classroom behaviors in second grade children, even after statistical adjustment for appropriate covariates. Consumption of two drinks per day or more on the average was related to a 7‐point decrement in IQ in 7‐year‐old children even after statistically adjusting for appropriate covariates. Low paternal education and more children in the household were identified as environmental factors exacerbating the effect of prenatal alcohol exposure on child IQ. Learning problems were associated with the alcohol “BINGE” pattern of five or more drinks on at least one occasion. This study shows that alcohol use patterns within the social drinking range can have long lasting effects on IQ and learning problems in young school aged children. These patterns should not be interpreted as biologic thresholds. It should also be noted that these are group effects of prenatal alcohol exposure, not necessarily predictable in the individual child, and that for the most part these children were functioning within the normal range of intelligence.
The Long‐Term Behavioral Effects of Prenatal Alcohol Exposure in Rats
Authors: Riley Edward P.
Published: April 2006

Prenatal exposure to alcohol can cause a variety of behavioral disturbances later in life. Many of the reports in animals of the behavioral teratogenic effects of alcohol have focused on assessing younger animals. The purpose of this paper is to review some of the longer lasting behavioral consequences of gestational alcohol exposure in animals. It is not meant as a comprehensive review, but rather focuses on selected studies. It is concluded that prenatal alcohol exposure does have long lasting effects, although some of these might only occur under challenging or stressful circumstances. It is hypothesized that as the animal matures compensatory mechanisms or strategies develop to compensate for these dysfunctions. Thus, behavioral problems may only be detected when these compensatory systems break down, either as a result of stress, because of complex testing procedures, or old age.
Neuroanatomic and Neurochemical Abnormalities in Non‐human Primate Infants Exposed to Weekly Doses of Ethanol during Gestation
Authors: Clarren Sterling K. , Astley Susan J. , Bowden Douglas M. , Lai Henry , Milam Ann H. , Rudeen P. Kevin , Shoemaker William J.
Published: April 2006

Ethanol was orally administered once per week to 54 gravid pigtailed macaques (Macaca nemestrina) in doses of 0.0, 0.3, 0.6, 1.2, 1.8, 2.5 or 4.1 gm/kg from the 1st week in gestation or in doses of 2.5, 3.3 or 4.1 gm/kg from the 5th week. Mean maternal peak plasma ethanol concentrations (MPPEC's) ranged from 24 ± 6 mg/dl at the 0.3 g/kg dose to 549 ± 71 mg/dl at the 4.1 g/kg dose. Thirty‐three live born infants were assessed for abnormalities of physical and behavioral development. Ocular pathology, neuropathologic and neurochemical assessments were done on 31 animals at 6 months postnatal age. Microphthalmia was noted in three of the 26 animals exposed to ethanol. Retinal ganglion cell loss was significantly associated with intra‐uterine ethanol exposure. Microphthalmia and retinal ganglion cell loss was observed in both the delayed and full‐gestational exposed animals. No structural anomalies were found in the brains via gross inspection or light microscopy. Chemical abnormalities in the striatal nuclei were identified. Striatal dopamine concentrations increased with increasing MPPEC exposure (0–249 mg/dl) among animals exposed weekly to ethanol throughout gestation. Striatal dopamine concentrations decreased with increasing MPPEC exposure (260–540 mg/dl) among animals whose weekly exposure to ethanol was delayed until the 5th week of gestation. The same pattern of association was also noted between MPPEC and ultrastructural alterations in the caudate nucleus. The extent of ultrastructural alterations increased with increasing MPPEC among the fullgestational exposed animals and decreased with increasing MPPEC among the delayed‐dose animals.
New Approaches to Research on the Long‐Term Consequences of Prenatal Exposure to Alcohol
Authors: West James R. , Goodlett Charles R. , Brandt Joan P.
Published: April 2006

As the summary presentation of a symposium on prenatal alcohol‐induced brain damage and long‐term postnatal consequences, this paper proposes the establishment of two main research priorities—to begin to correlate long‐term behavioral effects with alterations in underlying neural substrates, and to explore the mechanisms of neuroteratogenicity. To reach these goals, three objectives are described. First, animal and human research must become more interrelated. Second, experimental observations should be integrated into formal models that incorporate both neural structure and function. Third, researchers should choose well‐defined dependent measures that are derived from models of brain function based on modern concepts of cognitive neuroscience. Examples of neuropsychological tests that may serve as the bases for structure/function relationships are presented. Incorporating these objectives into future research will facilitate understanding of the fundamental issues concerning prenatal alcohol exposure and will begin to provide the bases for rational intervention or treatment.
Ethanol Causes Accelerated G1 Arrest in Differentiating HL‐60 Cells
Authors: Cook Robert T. , Keiner Judith A. , Yen Andrew
Published: April 2006

The effects of clinically relevant ethanol concentrations on myeloid differentiation in the HL‐60 cell promyelocytic leukemia line have been studied. The exposure of noninduced stem cells to 60 mm ethanol results in an increase in G1 cells, but there is no increase in superoxide production or expression of the Mo1 antigen. When HL‐60 cells are induced to differentiate along the myeloid line with dimethylsulfoxide (DMSO) or retinoic acid (RA), there is a shift to smaller cell size, an increase in G1 cells and acquisition of the ability to produce superoxide as reported previously by several authors. When ethanol is present during differentiation, there are further increases in G1 cells, and increases in the percentage of cells which produce superoxide and express Mo1, and decreases in mean cell size and total growth during the incubation period. Regrowth experiments after periods of differentiation indicate that the increased G1 arrest seen in the presence of ethanol represents terminal commitment if inducer is present, but in the absence of inducer the increased G1 percentage is readily reversible.

Examination of RNA content by flow cytometry reveals a decrease in both the peak and mean G1 RNA content during DMSO or RA induced differentiation. These decreases are accentuated by the presence of ethanol, resulting in a higher G1A/G1B ratio than in nonexposed cells.

These findings indicate that ethanol enhances G1 growth arrest in HL‐60 cells exposed to myeloid inducers. Partial differentiation occurs during this process, resulting in terminally arrested cells, some of which have undergone fewer postinduction cell divisions than normal and may not be fully competent.
Taste Reactivity in Alcohol Preferring and Nonpreferring Rats
Authors: Bice Paula J. , Kiefer Stephen W.
Published: April 2006

Taste reactivity tests were used to examine the orofacial responses of alcohol preferring (P) rats and alcohol nonpreferring (NP) rats to the taste of alcohol. In the initial exposure, naive rats were tested for reactivity to five concentrations of alcohol (5%, 10%, 20%, 30%, and 40% v/v), water, and one solution each of sucrose and quinine. A two‐bottle consumption test was then given for a 3‐week period to allow the rats access to 10% alcohol. After the preference test, a second taste reactivity test was done using the same solutions as in the initial reactivity test. The results indicated no significant differences in taste reactivity between P rats and NP rats on the initial exposure, except that NP rats made significantly more mouth movements. During the two‐bottle tests, consumption of alcohol by P rats was consistently higher than that of NP rats across all test days. On the second taste reactivity test, P rats showed an increase in the number of ingestive responses and a decrease in the number of aversive responses to alcohol. NP rats' taste reactivity to alcohol remained unchanged from Exposure 1 to Exposure 2. P rats' and NP rats' responses to sucrose and quinine did not change from Exposure 1 to Exposure 2. It was concluded that there were no innate taste response differences between P and NP rats to alcohol but that following alcohol experience, P rats showed a significant increase in ingestive responses and a concomitant decrease in aversive responses to the taste of alcohol. These data suggest that the taste of alcohol becomes more palatable to P rats after alcohol experience, a factor that may be important in the maintenance of continued high alcohol consumption by P rats.
Subject Selection Bias in Alcoholics Volunteering for a Treatment Study
Authors: Strohmetz David B. , Alterman Arthur I. , Walter Dan
Published: April 2006

Baseline differences in alcoholism problem severity were compared between alcoholics who did and did not volunteer to participate in a treatment effectiveness study. A positive relationship was found between self‐reports of alcohol‐related problems and the degree of research participation. Group differences were also revealed in the rate of treatment completion. Possible explanations and solutions for this volunteer bias are discussed.
Effects of Ethanol on Hexose Uptake by Cultured Rat Brain Cells
Authors: Singh Sant P. , Snyder Ann K. , Eman Svetlana
Published: April 2006

The effects of ethanol on hexose uptake by glial cells was investigated using primary cultures prepared from term rat fetuses. Specific 3H 2‐deoxy‐D‐glucose (2DG) uptake was significantly reduced by a 4‐hr exposure to ethanol at concentrations of 25, 50, and 100 mM, but not 200 or 300 mM. The inhibitory effect of 50 mM ethanol increased with the duration of exposure, with 2DG uptake inhibited by 36% after 18 hr. Astrocytes cultured from the brains of term fetuses of rats fed ethanol during pregnancy showed essentially the same 2DG uptake response to in vitro ethanol treatment. Kinetics of 2DG uptake showed a significant decrease of Vmax in the presence of ethanol. No interaction was found between ethanol and insulin, which stimulated 2DG uptake and protein content of the cultures. The data suggest that ethanol can modulate hexose uptake by astrocytes cultured from fetal rat brain. However, insulin actions on glial cells were not affected by ethanol.
Molecular Changes Associated with Ethanol‐Induced Growth Suppression in the Chick Embryo
Authors: Pennington Sam N.
Published: April 2006

In humans and in animal models the most frequently observed alcohol‐related birth defect (ARBD) is intrauterine growth retardation (IUGR). The central nervous system (CNS) is sensitive to the growth inhibitory effects of in utero ethanol exposure and neonatal CNS alterations with associated behavioral deficits are a likely result of maternal ethanol consumption. Presently, little information exists as to the biochemical mechanism by which ethanol inhibits fetal CNS growth. Further, it is unknown if there are genetic differences in maternal or fetal responses to ethanol. Ongoing research using a chick model indicates that pharmacologically appropriate doses of ethanol (< 30 mm) inhibit brain growth and reduce CNS 3′,5′‐cyclic adenosine monophosphate (cyclic AMP) with an associated 50% decrease in the binding of cyclic AMP by the regulatory subunit (RII) of protein kinase A. Furthermore, there is a specific loss of phosphorylation of RII by kinase catalytic subunit as a result of ethanol exposure. Because tissue cyclic AMP content and the degree of RII phosphorylation are important parameters for the regulation of protein kinase A catalytic activity, it is hypothesized that these alterations may be biochemical transformations that underlie ethanol‐induced growth suppression.
Alcohol Induction of Ferritin Expression in a Human Hepatoblastoma Cell Line (HEP G2)
Authors: Moirand Romain , Lescoat Gérard , Hubert Noëlla , Dezier Jean Francois , Pasdeloup Nicole , Brissot Pierre
Published: April 2006

Hyperterritinomla, an unclear mechanism, is frequently observed in chronic alcoholics. The aim of this work was to study the effect of alcohol on ferritin expression in a human hepatoblastoma cell line, HepG2. This cell line proved to be sensitive to alcohol, since alcohol increased γ‐GT activity both in cells and media. The most striking result was the increase of ferritin in cells and media by alcohol. Moreover, this effect was specific, since it contrasted with a decrease in total protein synthesis and secretion, a decrease in transferrin excretion and a lack of effect on orosomucoid. In our model, alcohol was able to induce, in a specific manner, ferritin expression.
Overall Functioning and Criteria of Progress in Rehabilitation of Alcohol Abusers: Longitudinal Analyses of Changes
Authors: åkerlind Ingemar , Hörnquist Jan Olof , Elton Martin , Bjurulf Per
Published: April 2006

The aim was to compare alcohol consumption and vocational adjustment as criteria of rehabilitation progress of alcoholics, with regard to links to concomitant changes in functioning in other life areas. Thirty‐four advanced alcohol abusers in rehabilitation were examined twice with an interval of 2 years between each examination. Change scores in alcohol consumption and work capacity were correlated with change scores in social network, activities, life‐satisfaction, psychological well‐being, psychiatric symptoms, and biomedical functioning. Improved drinking habits were connected with some changes in overall functioning, however not solely in a favorable direction. Negative mood changes were especially note‐worthy. Improvements in vocational adjustment, on the other hand, appeared to be somewhat more unequivocally and encompassingly associated with amelioration in the wider range of functioning. The results indicate that drinking measures alone are not sufficient indicators of progress in rehabilitation and underscores the need more global criteria of general adjustment.
Alcohol Use by Alcoholics with and without a History of Parental alcoholism
Authors: Worobec Thomas G. , Turner Winston M. , O'Farrell Timothy J. , Cutter Henry S. , Bayog Rogelio D. , Tsuang Ming T.
Published: April 2006

The association between parental history of alcoholism and the nature of alcoholism was assessed using a more reliable measure of family history (Family Tree Questionnaire) and a more comprehensive inventory of alcoholism (Alcohol Use Inventory) than used in earlier studies. Parental alcoholism was associated with more severe alcoholism on most parameters of alcohol use (age of onset, quantity, frequency, preoccupation, and sustained use) and alcohol‐related problems (social, vocational, physical, cognitive, and loss of control). The association between parental history of alcoholism and more severe alcoholism in the probands was independent of age of onset of alcoholism, current age, socioeconomic background, and marital status.

Parental history positive (PH+) alcoholics were more reliant on alcohol to manage their moods but did not differ significantly from parental history negative (PH‐) alcoholics in the use of alcohol to improve sociability or mental functioning or to cope with marital problems. Surprisingly, the degree of concern, guilt, and worry over the negative consequences of drinking was not significantly different for PH+ alcoholics although the negative consequences were clearly much more severe for this group. While the data are inconclusive about the reasons for more severe alcoholism in PH+ alcoholics, greater reliance on ethanol to manage moods and a relative insensitivity to negative consequences could theoretically account for the vulnerability to more severe alcoholism found in PH+ alcoholics.
The Adrenocortical Response to Brain Injury: Correlation with the Severity of Neurologic Dysfunction, Effects of Intoxication, and Patient Outcome
Authors: Woolf P. D. , Cox C. , Kelly M. , Nichols D. , McDonald J. V. , Hamill R. W.
Published: April 2006

To test the hypothesis that cortisol levels reflect the extent of neurologic dysfunction and predict patient outcome, neurologic function and cortisol levels were determined in 120 traumatically brain injured patients who never received glucocorticoid treatment. Their mean age was 29 years and 78% were men. The impact of intoxication was examined in 59 patients who had ethanol levels measured. Ethanol was detectable in 40 patients and ≥ 100 mg/dl in 31. There were significant correlations between the extent of neurologic dysfunction, determined by the Glasgow Coma Score and plasma cortisol concentrations 1 and 4 days postaccident. Cortisol levels were universally elevated on admission and approached normal 7 days later. Multiple linear regression analysis revealed significant effects of circulating ethanol levels on the association between cortisol concentrations and progressively worsening neurologic function, i.e., ethanol reduced the magnitude of the cortisol elevations in a dose dependent manner, abolishing this relationship at levels above 100 mg/dl. Analysis of the relationships between circulating cortisol levels and patient outcome provided a second method for ascertaining the association between injury severity and the magnitude of adrenocortical activation. Admission and day 1 cortisol concentrations were 25 to 40% lower in patients having good recoveries or moderate disabilities than those who remained severely disabled, persistently vegetative or died; serum cortisol values of < 20 μg/dl one day after the accident were more likely to be associated with a good outcome than a poor one (55 vs. 25%, p < 0.001). The worsening prognosis of patients having higher cortisol values is further reflected in the duration of acute hospitalization of these individuals. Thus, in an acute brain injury paradigm there is an excellent time dependent relationship between the severity of illness and the degree of activation of the adrenal cortex. This is reflected in the significant relationship between circulating cortisol levels and the magnitude of neurologic dysfunction and between cortisol concentrations and patient outcome. Ethanol, a frequent compounding factor in head injury, however, moderates the initial adrenocortical response through mechanisms that await clarification.
Ethanol and (Na+,K+)‐ATPase: Alteration of Na+‐K+ Selectivity
Authors: Swann Alan C.
Published: April 2006

Relative internal concentrations of Na+ and K+ are important in regulating (Na+,K+)‐ATPase in situ. Ethanol is known to inhibit (Na+,K+)‐ATPase and to reduce K+ affinity, but the concentrations required for these effects in vitro are large compared with those probably attainable in vivo. Yet, there is evidence suggesting that ethanol has physiologically relevant effects on (Na+,K+)‐ATPase. We have investigated the effects of ethanol on selectivity for Na+ versus K+. At 150 mM, ethanol had little effect on (Na+,K+)‐ATPase activity under the usual assay conditions, slightly (but nonsignificantly) reduced K+ affinity, and had no effect on extrapolated Na+ affinity in the absence of K+. However, ethanol had marked effects on cation selectivity, doubling the K, for K+ on Na+ affinity and halving the K, for Na+ on K+ affinity. These data show that ethanol, at concentrations too small for effects on (Na+,K+)‐ATPase activity under optimal assay conditions, can alter its responses to changes in Na+ or K+.
The Pulsatile Secretion of Gonadotropins and Growth Hormone, and the Biological Activity of Luteinizing Hormone in Men Acutely Intoxicated with Ethanol
Authors: Välimäki Matti , Tuominen Juha Antti , Huhtaniemi Ilpo , Ylikahri Reino
Published: April 2006

The effects of acute alcohol ingestion were studied on pulsatile secretion of immunoreactive luteinizing hormone (LH), follicle‐stimulating hormone (FSH), and growth hormone (GH), and on serum bioactive LH, testosterone, cortisol, and prolactin. A dose of 1.5 g ethanol per kg of body weight was administered by mouth to eight healthy male volunteers (aged 20 to 26 years) during 3 hr from 1800 to 2100 hr. Blood samples were collected every 20 min for 20 hr until 1400 hr of the following day. Each subject served as his own control in an identical experiment without ethanol, carried out at least 1 month later. Ethanol ingestion decreased serum testosterone concentration on average by 23% (p < 0.05) between 10 and 16 hr after starting the drinking. The mean levels of LH and FSH and the mean number and amplitude of LH and FSH pulses remained unchanged. Ethanol ingestion did not affect the biological activity of LH. In each subject alcohol administration reduced the nightly peak of GH secretion, and in addition, changed the timing of this peak in most subjects. Only marginal changes were found in the prolactin levels but ethanol ingestion increased the cortisol levels on average by 36% (p < 0.05) between 11 and 14 hr after the start of drinking. We conclude that the decrement in serum testosterone evoked by ethanol is not attributable to impaired pulsatile secretion of gonadotropins nor to reduced biological activity of LH. In contrast, ethanol profoundly suppressed the pulsatile secretion of growth hormone.
Human Gastric Alcohol Dehydrogenase: Its Inhibition by H2‐Receptor Antagonists, and Its Effect on the Bioavailability of Ethanol
Authors: Hernández‐Muñoz Rolando , Caballeria Joan , Baraona Enrique , Uppal Rajiv , Greenstein Robert , Lieber Charles S.
Published: April 2006

Two types of alcohol dehydrogenase isoenzymes (differing in their affinity for ethanol, sensitivity to 4‐methylpyrazole, and electrophoretic migration) have been identified in the human stomach. At the high ethanol concentrations prevailing in the gastric lumen during alcohol consumption, the sum of their activities could account for significant oxidation of ethanol. In vitro, these activities were inhibited by cimetidine and ranitidine, but not by famotidine. In vivo, therapeutic doses of cimetidine (but not of famotidine) increased blood ethanol levels when ethanol was given orally, but not when it was given intravenously, indicating a significant contribution of the gastric ADH to the bioavailability and thereby the potential toxicity of ethanol.
Plasma Protein Catabolism in Ethanol‐ and Colchicine‐ Treated Liver Slices
Authors: Donohue Terrence M. , Chaisson Mary L. , Zetterman Rowen K.
Published: April 2006

The present study was conducted to determine whether the antisecretory agents colchicine and ethanol affect the intracellular degradation of plasma proteins in rat liver. Plasma proteins were prelabeled in vivo with [3H]leucine and their levels were monitored immunochemically in both the medium and extracts of rat liver slices incubated alone or in the presence of 50 μM colchicine or 25 mM ethanol. Compared with those left untreated, colchicine‐treated slices had a 40‐55% lower secretory capacity and, at one point, showed significant hepatocellular retention of total plasma proteins. Plasma protein secretion by ethanol‐treated liver slices was 22‐32% lower than controls, but there was no detectable retention of unsecreted plasma proteins in the ethanol‐treated liver tissue. In all experiments, the total radioactivity in plasma proteins (i.e., the immunoprecipitable radioactivity in the liver plus that in the medium) decreased with time in a manner suggestive of intracellular degradation. Regression analyses of the rates of degradation of presecretory proteins revealed that compared with controls, plasma protein catabolism was accelerated 57% in colchicine‐treated slices. In ethanol‐treated liver slices, there was a 50% increase in the degradation of total plasma proteins and a 46% increase in albumin catabolism. In all cases, degradation was intracellular. These findings indicate that inhibition of hepatic protein secretion by either colchicine or ethanol is associated with accelerated catabolism of unsecreted plasma proteins, suggesting that hepatocellular degradative processes are responsive to changes in the levels of presecretory proteins and/or perturbations of the secretory process.
Suppression of Natural Killer Cell Activity by Ethanol Consumption and Food Restriction
Authors: Blank S. E. , Duncan D. A. , Meadows G. G.
Published: April 2006

Effects of 4‐week food restriction and ethanol consumption on natural killer (NK) cell activity and carcass composition were evaluated. Female, C57BL/6 mice given water (H2O) or ethanol (20% w/v, ETOH) ad libitum were placed in one of three dietary groups: unrestricted (UNR), moderately restricted (MR, 2.2 g/day), or severely restricted (SR, 1.8 g/day).

Food restriction alone (MR, SR) significantly reduced body, spleen, and thymus weights; carcass lipid content (SR only); spleen cell number; and baseline and interleukin‐2 (rlL‐2) stimulated NK cell activities. Ethanol consumption was unaffected by food restriction and in restricted mice it did not suppress food intake. Thus, average calories derived from ethanol increased from 30% (UNR) to 40% (SR) with the degree of food restriction in these groups. Mice given ethanol and restricted food intake had at least as heavy or heavier body, spleen, and thymus weights than water‐drinking (H2O) counterparts. Spleen cell number was reduced in ethanol‐consuming (ETOH), food restricted groups compared with UNR H2O control. Baseline NK cell activity was suppressed 50% to 90% in all ETOH and food‐restricted groups. rlL‐2 stimulated NK cell activity was suppressed 18% to 76% in food restricted mice independent of ethanol intake. These results indicate that supplementary ethanol calories did not enhance NK cell activity in UNR ETOH mice, nor did they protect splenic NK cell activity from the suppressant effects of food restriction.

Ethanol consumption significantly increased carcass lipid content in all groups compared with their H2O counterparts. This increase was largely responsible for the preservation of body weight in ETOH mice especially during food restriction. Therefore, caution must be exercised when using body weight as an indicator of nutritional status for ETOH mice.
The Structure of Drinking‐Related Consequences in Alcoholic Women
Authors: Turnbull Joanne E. , Gomberg Edith S.L.
Published: April 2006

This study examines the structure of drinking‐related consequences in women in treatment facilities by describing indices that were constructed by submitting 69 measures to factor analysis. Two hundred fifty‐four (254) alcoholic women responded to self‐report interview items that measured the consequences that the respondent perceived to follow or result from her drinking. The items were submitted to a series of exploratory principal component analyses. Nine factors, social withdrawal, sexuality, early effects, maternal role, accidents, symptoms, work, illness, and relationship conflict, emerged in the rotated solution, with the majority of coefficient alphas in the 0.6 to 0.8 range. Internal reliabilities for the indices remained sufficiently high across age subgroups in the sample.
Alcoholic Liver Disease: Pathologic, Pathogenetic and Clinical Aspects
Authors: Ishak Kamal G. , Zimmerman Hyman J. , Ray Mukunda B.
Published: April 2006

Alcoholic liver disease includes steatosis, alcoholic hepatitis and cirrhosis. Other liver diseases of genetic origin, but with a curious association with alcohol intake, are hemochromatosis and porphyria cutanea tarda. The attribution of chronic hepatitis to alcohol intake remains speculative, and the association may reflect hepatitis C infection. Hepatic injury attributed to alcohol includes the changes reported in the fetal alcohol syndrome.

Steatosis, the characteristic consequence of excess alcohol intake, is usually macrovesicular and rarely microvesicular. Acute intrahepatic cholestasis, which in rare instances accompanies steatosis, must be distinguished from other causes of intrahepatic cholestasis (e.g., drug‐induced) and from mechanical obstruction of the intrahepatic bile ducts (e.g., pancreatitis, choledocholithiasis) before being accepted. Alcoholic hepatitis (steatonecrosis) is characterized by a constellation of lesions: steatosis, Mallory bodies (with or without a neutrophilic inflammatory response), megamitochondria, occlusive lesions of terminal hepatic venules, and a lattice‐like pattern of pericellular fibrosis. All these lesions mainly affect zone 3 of the hepatic acinus. Other changes, observed at the ultrastructural level, are of importance in progression of the disease. They include widespread cytoplasmic shedding, and capillarization and defenestration of sinusoids. Progressive fibrosis complicating alcoholic hepatitis eventually leads to cirrhosis that is typically micronodular but can evolve to a mixed or macronodular pattern. Hepatocellular carcinoma occurs in 5 to 15% of patients with alcoholic liver disease.

The clinical syndrome of alcoholic liver disease is the result of three factors—parechymal insufficiency, portal hypertension and the clinical consequences of extrahepatic damage produced by alcohol. At the several phases of the life history of alcoholic liver disease, the individual factors play a different role. The clinical manifestations of alcoholic steatosis are mainly extrahepatic in origin. Those of alcoholic hepatitis reflect mainly parenchymal insufficiency and those of cirrhosis are mainly those of portal hypertension.

Alcoholic liver injury appears to be generated by the effects of ethanol metabolism and the toxic effects of acetaldehyde, perhaps the immune responses to alcohol‐ or acetaldehyde‐altered proteins, and questionably enhanced by viral hepatitis.

Alcoholic hepatitis may be mimicked histologically, and to a varying degree clinically, by a number of conditions (obesity, diabetes, several drug‐induced injuries, jejunoileal bypass, and related “short‐circuiting” of the bowel). Perhaps the most important facet of the hepatotoxicity of alcohol is its enhancement of the effects of a number of other hepatotoxic agents, among which acetaminophen in the example.
The Effect of Desglycinamide‐(ARG8)‐Vasopressin (DGAVP) on the Acquisition of Free‐Choice Alcohol Drinking in Rhesus Monkeys
Authors: Kornet M. , Goosen C. , Ribbens L. G. , Van Ree J. M.
Published: April 2006

The vasopressin analog desglycinamide‐(Arg8)‐vasopressin (DGAVP) has been reported to reduce the acquisition of heroin and cocaine self‐injection behavior in rats. This led to the hypothesis that DGAVP can reduce the self‐administration of psycho‐active drugs (including ethanol) by attenuating central reinforcement processes. Under forced ingestion conditions, DGAVP has been reported, however, to enhance alcohol drinking in rats. We studied the effect of DGAVP on the acquisition of voluntary, free‐choice alcohol drinking in naive rhesus monkeys, that had concurrent access to either 1% and 2% (n = 12) or to 4% and 8% (n = 8) ethanol/water solutions in addition to drinking water. Half of the monkeys were injected twice per day with 50 μg. kg‐1 of DGAVP for 14 successive days, the other half received placebo. Subsequently, all subjects had access to the same solutions for another 14 days without treatment. DGAVP did not significantly affect concentration preference behavior. With regard to net ethanol ingestion in animals drinking 1% and 2% solutions, DGAVP decreased net ethanol intakes, having a time‐dependent and long lasting effect; placebo‐treated animals gradually increased net ethanol intakes over time. The placebo‐treated animals in the 4% and 8% group, showed a different acquisition pattern; DGAVP reduced net ethanol intake in two animals in a similar way as above. Two animals behaved differently. It is concluded that in a free‐choice condition DGAVP did not enhance the acquisition of alcohol drinking in monkeys, but rather inhibited ethanol self‐administration in the majority of the subjects.
Acute in Vivo Effects of Low Ethanol Concentration on the Capacity of Urea Synthesis in Rats
Authors: Jensen Søren Astrup , Almdal Thomas Peter , Vilstrup Hendrik
Published: April 2006

We studied the effect of acute exposure, by constant intravenous infusion, to a low blood ethanol concentration (range 8‐14 mmol/l) on the in vivo capacity of urea‐N synthesis (CUNS), alanine elimination, and the nitrogen retention in fed and fasted rats. Alanine was infused to obtain a constant blood concentration of a‐amino nitrogen between 7.3 and 11.7 mmol/1, at which concentrations urea synthesis is at maximum.

CUNS was calculated after nephrectomy as accumulation of urea in body water, elimination of alanine as alanine infusion rate corrected for accumulation, and nitrogen retention as the difference.

In the fed state ethanol decreased CUNS from 7.84 ± 0.32 μmol N/(min 100 g body weight (BW)) (mean ± SEM) (n = 7) to 6.30 ± 0.58 (n = 6) (p <0.001) and in the fasted state from 8.25 ± 0.27 μmol N/ (min 100 g BW) (n = 10) to 6.90 ± 0.25 (n = 10) (p <0.001).

In the fed state ethanol increased the elimination of alanine from 6.49 ± 0.28 μmol/ (min 100 g BW) (n = 7) to 6.95 ± 0.25 (n = 6) (p <0.01), and in the fasted state decreased it from 6.25 ± 0.12 μmol/ (min 100 g BW) (n = 10) to 5.67 ± 0.20 (n = 10) (p <.001).

In the fed state nitrogen retention was changed by ethanol from‐1.35 ± 0.53 μmol/ (min 100 g BW) (n = 6) to 0.65 ± 0.77 μmol/(min 100 g BW) (n = 7) (p <0.001), and in the fasted state from‐2.0 ± 0.27 μmol/(min 100 g BW) (n = 10) to‐1.23 ± 0.30 μmol/(min 100 g BW) (n = 10) (p <0.001).

The effects of acute exposure to low ethanol concentration on CUNS and nitrogen retention were abolished in rats pretreated with methylene blue.

It is concluded that acute exposure to low ethanol concentrations transiently leads to suppression of the capacity of urea synthesis, presumably due to the decrease in NAD/NADH ratio during metabolism of ethanol.
Effect of Acute Ethanol on Esophageal Motility in Cat
Authors: Keshavarzian Ali , Urban Glenn , Sedghi Shahriar , Willson Christopher , Sabella Linda , Sweeny Christopher , Anderson Karen
Published: April 2006

In man, acute ethanol administration decreases lower esophageal sphincter pressure (LESP), prolongs the duration, and lowers the amplitude of esophageal contractions. These changes may contribute to gastroesophageal reflux and esophagitis. To evaluate the underlying mechanisms of these changes an animal model is needed. Hence, we studied the effect of various doses of ethanol on esophageal motility in cats, an animal with an esophagus similar to man's. Similar to man, intravenous administration of ethanol significantly decreased LESP and amplitude of lower (smooth muscle portion) esophageal contractions. It also prolonged the duration of lower esophageal contractions, even through it had no effect on contraction velocity. The effect of ethanol on upper (striated muscle portion) esophagus was different. Ethanol had no effect on the amplitude of contractions, whereas it prolonged their duration and decreased their velocity. The effect of acute ethanol on LESP in four withdrawing alcoholic cats was similar to controls. However, the acute effect of ethanol on the esophageal contractions was less marked in alcoholics. Bilateral cervical vagotomy and intravenous injection of the neurotoxin tetrodotoxin before the administration of ethanol did not prevent the effect of ethanol on LESP. This data suggests that cat esophagus is a good model for studying the underlying mechanisms of the effects of acute ethanol because its response is similar to the esophagus of man, and the acute effect of ethanol on LESP is not neurally mediated but is the result of its direct effect on muscle.