bluuebunny/crossref_metadata_2025 huggingface dataset:
A Placebo‐Controlled Double‐Blind Comparative Clinical Study of the Disulfiram‐ and Calcium Carbimide‐Acetaldehyde Mediated Ethanol Reactions in Social Drinkers
Authors: Peachey J. E. , Zilm D. H. , Robinson G. M. , Jacob M. , Cappell H.
Published: February 2008

Treatment for 2 days with disulfiram (3.5 mg/kg once daily) and calcium carbimide (0.7 mg/kg twice daily) in social drinkers produced, as compared to controls, simllar blood ethanol values, 2– to 3‐fold increases in blood acetaldehyde, respectively, and increased heart rate, pulse pressure, skin temperature, and flushing following 0.15 g/kg of ethanol taken 12 hr after the last drug admlnistration. Peak blood acetaldehyde concentration was greater for calcium carbimide compared to disulfiram (p < 0.05) and subjects treated with calcium carbimide experienced greater discomfort compared to disulfiram due to palpitations and shortness of breath, and they reported less intention to drink durlng the reaction. However, neither drug produced sufflclent aversion to curtail further drlnklng totally. With repeated drinks, there was an overall reduction of blood acetaldehyde concentration for calcium carbimide of 85% and for disulfiram of 35%. These data may provide a biochemical basis for the claims of certain alcoholics that they can drink to “burn off” the effects of these drugs.
Acute Ethanol Treatment Modifies Response Properties and Habituation of the DR‐VR Reflex in the Isolated Frog Spinal Cord
Authors: Rinaldi P. C. , Nishimura L. Y. , Thompson R. F.
Published: February 2008

Ethanol modification of habituation, a fundamental form of behavioral plasticity, was examined in the isolated frog spinal cord preparation. The polysynaptic dorsal root to ventral root (DR‐VR) reflex response was assessed in normal Ringer's and at one of four ethanol concentrations. The reflex itself was facllitated at lower levels (0.025%) and depressed at higher levels (0.05–0.5%) Of ethanol. Habituation, decrement of the polysynaptic ventral root response to repeated dorsal root stimulatlon, was reduced at all ethanol concentrations. Understanding the mechanisms of ethanol action involved in the disruptlon of simple forms of plasticity will help us to explain Its actions on more complex forms of associa‐tional processes.
The Metabolic Fate of Double‐Labeled Disulfiram
Authors: Neiderhiser Dewey H. , Wych Gregory , Fuller Richard K.
Published: February 2008

The metabolic fate of disulfiram labeled with both 14C and 35S was studied in the rat. After administration of 50 mg of 14C,35S‐disulfiram dissolved in corn oil to rats by stomach tube, 95% of the radioactivity was recovered in urine, feces, and expired air at 144 hr. The major portion of the excreted radioactivity was in urine (75 ± 6%). Feces and expired air contained 13 ± 2% and 6 ± 5% of the dose, respectively. No measurable radioactivity was found in the body organs or carcass. Pretreatment of rats with unlabeled disulfiram for 20 days prior to administration of 14C,35S‐disulfiram led to more rapid catabolism of the drug and more rapid excretion of radioactivity in the urine during the first 12 hr after dosing.
Identification and Intervention of Heavy Drinking in Middle‐Aged Men: Results and Follow‐up of 24–60 Months of Long‐Term Study with Randomized Controls
Authors: Kristenson Hans , Öhlin Hans , Hultén‐Nosslin Maj‐Britt , Trell Erik , Hood Bertil
Published: February 2008

In a continuing screening and intervention programme in Malmó, elevated serum‐yglutamyltransferase (GGT) values were used for selection of heavy drinkers. The study population consisted of 585 individuals born 1926–1933 with two consecutive GGT values in the upper decile of the GGT distribution, randomly allocated either to an intervention group of to a control group. The subjects in the intervention group were further investigated and 75% of them were judged to have elevated GGT values caused by alcohol consumption. These individuals were repeatedly encouraged to lower their overall alcohol consumption and GGT measurements were used as biofeedback method in the treatment program. The controls were informed by letter to be restrictive with their alcohol consumption and that they should receive new invitations for measurements of their liver enzymes after 2, 4, and 6 years. The intervention and control groups were well matched and followed over a 2–6‐year period.

Two and 4 years after the screening investigation, the GGT values in both groups were significantly decreased. There were differences, however, between the two groups with regard to sick absenteeism, hospitalization, and mortality. A significant reduction was found in sick absence during 4 years by 80%, in hospital days during 5 years by 60%, and in mortality during 6 years by 50% in the intervention group compared with the control group. Thus, the intervention program was effective in preventing medico‐social consequences of heavy drinking.
Influence of Ethanol on Reproductive Functions of the Adult Male Rat as a Function of Body Weight
Authors: Rivier Catherine , Vale Wylie
Published: February 2008

Adult male rats were exposed to alcohol vapors for 3–4 weeks. Blood alcohol levels (BAL) ranged from 90 to 190 mg/100 ml. BAL of ≥ 0–130 mg/100 ml were compatible with adequate body weight gains and were not associated with diminished plasma testosterone (T) levels or reduced sex organ weights. BAL ≥ 180 mg/100 ml were associated with inhibition of androgen secretion only in those anlmals who failed to grow. From these results we conclude that in growing animals, the medium term exposure to ETOH leads to inhibition of reproductive parameters when high BALs induce weight loss, but not when adequate body growth is maintained.
Effects of Oral Administration or Implantation of Disulfiram on Aldehyde Dehydrogenase Activity in Human Blood
Authors: Hellstrom E. , Tottmar O. , Widerlöv E.
Published: February 2008

The goneral characteristics of the NAD‐dependent aldehyde dehydrogenase (ALDH) present in blood were examined to find suitable assay conditions for activity measurements with whole blood samples from disulfiram‐treated patients. The ALDH activity was measured as the rate of acetaldehyde disappearance. The ALDH activity in blood from alcoholics before disulf iram treatment was 39% lower than that found in blood from control subjects. Disulfiram caused a decreased ALDH activity in vitro. Similarly, a decreased activity was found in blood from patients treated with disulfiram orally (400 mg/ day). The activity declined to a level being 60% of the control activity during the first week of treatment. A significant inhibition was Observed 1 week after the treatment was discontinued. Implantation of 1 g of disulfiram in patients pretreated for 10 days with oral disulfiram did not cause a delayed return of ALDH activity, suggesting that the amounts of disulfiram released were too low to affect the ALDH activity in blood.
Predictors of Mortality in Alcoholic Women: A Prospective Follow‐up Study
Authors: Smith Elizabeth M. , Cloninger C. Robert , Bradford Susan
Published: February 2008

An 11‐year follow‐up of 100 alcoholic women who were systematically interviewed and diagnosed during hospitalization found 31% dead, the majority as a result of alcohol‐related causes. There were over 4 times as many deaths in alcoholic women as expected in the general population. The life span of alcoholic women was shortened by over 15 years. Only those women who had abstained during the interval followlng hospitalization had fewer than expected deaths. Five variables correctly predicted survival status for 79% of the subjects (80% of survivors and 77% of those who died): older age at index, onset of alcoholism before age 30, history of frequent benders, primary diagnosis of antisocial personality, and short‐term drinking status.
Alcohol‐Induced Euphoria Enhanced by Disulfiram and Calcium Carbimide
Authors: Brown Zavie W. , Amit Zalman , Smith Brian R. , Sutherland E. Ann , Selvaggi N.
Published: February 2008

In a double‐blind study, subjects were treated with either disulfiram or calcium carbirnide, inhibitors of acetaldehyde elimination, prior to consumption of low doses of alcohol. Self‐rating scales, individual interviews, and observations by independent judges revealed that experimental subjects manifested enhanced changes in mood and euphoria compared to placebo control subjects.
Cardiovascular Effects of Acetaldehyde Accumulation after Ethanol Ingestion: Their Modification by β‐Adrenergic Blockade and Alcohol Dehydrogenase Inhibition
Authors: Kupari Markku , Lindros Kai , Hillbom Matti , Heikkila Juhani , Ylikahri Reino
Published: February 2008

Left ventricular function was examined by echocardiography and systolic tlme intervals in nine healthy male volunteers, who ingested ethanol 0.35 g/kg 4 hr after a Smg peroral dose of calcium cyanamide, an aldehyde dehydrogenase inhibitor. Accumulation of acetaldehyde in blood was accompanied by marked increases in heart rate (53%) and cardiac output (78%) as well as by decreases in diastolic arterial blood pressure (19%) and peripheral vascular resistance (46%). Ejection fraction and maximum circumferential fibre shortening velocity increased by 25 and 47%, respectively: the preejection period/ejection time ratio decreased by 31%. 4‐Meth‐ylpyrazok, an alcohol dehydrogenase inhibitor, efficiently reduced blood acetaldehyde levels when injected intravenously (7 mg/kg) at the height of the reaction. It was as effective as intravenous propranolol (0.1 mg/kg) in attenuating the hyperdynamic circulation and stabilized arterial blood pressure better than propranolol. We conclude that even a very mild alcohol intoxication (30–50 mg/100 ml) causes a marked enhancement of cardlac function, in addition to vesodllation, in subjects with impaired acetaldehyde oxidation. These changes are reversed by preventing acetaldehyde formation through alcohol dehydrogenase inhibition.
Acute Effects of Alcohol on Female Sex Hormones
Authors: MD Matti Välimäki. , Härkönen Matti , Ylikahri Reino
Published: February 2008

The acute effect of alcohol on plasma concentrations of female sex hormones was studied in nine healthy women aged 20–32 years during the midluteal phase of menstrual cycle. The experimental subjects received alcohol (1.2 g/kg of body weight) during the first 3 hr of the experiment (from 18.00 to 21.00 hr) and the plasma concentrations of folliclestimulating hormone, luteinizing hormone, Prolactin, estradiol, estrone, progesterone, testosterone, and growth hormone were monitored for 20 hr after the start of the experiment. Every subject also participated in an identical control experiment without alcohol at the same phase of the next or previous cycle. Blood alcohol concentration reached its maximum 1.19 ± 0.02 g/liter (mean ± sem) 4 hr after the start of drinking. We could not demonstrate any alcohol‐induced decrease in plasma concentrations of estradiol, estrone, progesterone, and testosterone. In contrast, the relative values for plasma concentrations of estradiol, progesterone, and testosterone as calculated as per cent of the starting hormone levels tended to be even higher after alcohol administration than during the control session. During the first 4 hr of the oxperiment, plasma concentrations of gonadotropins seemed to decrease more rapidly after ethanol ingestion than during the control session, possibly due to negative feedback regulation of pituitary gonadotropin secretion by the relative high level of plasma estradiol, or due to a direct effect of ethanol administration. With ascending blood ethanol concentration, the values for plasma prolactin were decreased. The peak concentration of plasma growth hormone seen at 4 hr during the control session was totally abolished by ethanol ingestion.

In conclusion, our results suggest that the acute ingestion of moderate doses of alcohol has only small effects on female gonadal function during the luteal phase of the menstrual cycle.
Lipofuscin Granules in Purkinje Cells after Long‐Term Alcohol Consumption in Rats
Authors: Tavares M. A. , Paula‐Barbosa M. M.
Published: February 2008

The increased number of lipofuscin granules in Purklnje cells from chronic alcohol‐fed rats was studied by morphometric methods. These granules were autofluorescent and had marked acid phos‐phatase activity. No significant changes were found in the mean nuclear and perikaryon volumes when alcohol‐fed and control groups were compared. The number of lipofuscin granules per unit of surface area of cell cytoplasm (Na) and their volumetric density (V), were significantly greater in alcohol‐fed groups than in controls. These values were also significantly different when the 6– and 12‐month control groups were compared. Na and V, values in alcohol‐fed groups increased progressively. The increased number is probably related to disturbances in neuronal cell metabolism. The importance of age and malnutrition in the formation of these granules was also considered.
Diethyldithiocarbamic Acid‐Methyl Ester Distribution, Elimination, and LD50 in the Rat after Intraperitoneal Administration
Authors: Faiman Morris D. , Artrnan Linda , Maziasz Tim
Published: February 2008

Following the intraperitoneal administration of S35 diethyldithiocarbamic acid‐methyl ester (S35 DDTC‐Me) to male rats, maximal total radioactivity (S35) in most tissues was found 1 hr after dosing. Twelve hr after intraperitoneal S35 DDTC‐Me, most of the total radioactivity was found in urine. The feces accounted for approximately 15% of the total radioactivity. No radioactivity was detected in the breath. The kidney exhibited the greatest uptake of radioactivity, while the least uptake was found in the brain and heart. Most of the radioactivity in the tissues was due to the inorganic sulfate. S35 DDTC‐glucuronide was found in the gastrointestinal tract and feces. The LD50 for DDTC‐Me given intraperitoneally to male rats and mice was 167 and 263 mg/kg, respectively. Symptoms of toxicity proceeding death of the animals resembled those symptoms observed with disulfiram toxicity.
Clinical and Biochemical Course of Alcoholic Liver Disease Following Sudden Discontinuation of Alcoholic Consumption
Authors: Marshall John B. , Burnett David A. , MD Rowen K. Zetterman. , Sorrell Michael F.
Published: February 2008

It has been our impression that clinical deterioration and worsening of liver tests of patients with alcoholic liver disease (ALD) is common immediately following hospitalization and cessation of ethanol intake. In order to determine the frequency of such deterioration and characterize features which may identify those patients who initially deteriorate, we analyzed the standard liver tests and Clinical parameters of liver function following hospltaltzation of 273 cases of ALD, and correlated these with histologic patterns and hospital course. We found that moderate liver test worsening following hospitalization is frequent in patients with ALD, especially alcoholic hepatitis. The presence of alcoholic hyalin in patients with alcoholic hepatitis did not correlate with liver function or frequency of biochemical worsening, but did correlate with mortality. Biochemical deterioration did not correlate with clinical deterioration or mortality, unless complications such as bleeding, sepsis, or pancreatltls occurred. Spontaneous clinical deterioration of our patients in the absence of precipitating factors was rare. We conclude that worsening of liver tests following hospitalization frequently occurs in patients with ALD, does not necessarily imply presence of complications (e.g., biliary obstruction, sepsis, other liver injury), but should suggest the presence of alcoholic hepatitis.
Alcohol Use in Youthful Methadone‐Maintained Former Heroin Addicts: Liver Impairment and Treatment Outcome
Authors: Hartman N. , Kreek M. J. , Ross A. , Khuri E. , Millman R. B. , Rodriguez R.
Published: February 2008

Combined alcohol abuse and narcotic dependency is now recognized as a common problem in adults but has not been well characterized in adolescents, nor have the effects of combined substance abuse on liver function in this age group been assessed. Forty‐four youthful former heroin addicts (27 males (M) and 17 females (F)) on methadone maintenance therapy were interviewed in detail about past and present alcohol use and underwent physical examination. Liver function studies and tests for hepatitis B antigen and antibody were performed. Four and onehalf years later, 28 of these patients still in treatment or willing to return for study purposes were similarly reevaluated. The original sample included 15 whose alcohol intake was high (12 M + 3 F: group A) and 29 whose intake was low or absent (15 M + 14 F: group N). Sixty‐six per cent of group A patients and 58% of group N patients remained in treatment at the second time point. Group A had significantly greater abnormalities in liver function than group N with evidence of progression over 4 1/2 years, based both on physical examination and blood chemistry results. Seventy‐five per cent of the patients had evidence of exposure to hepatitis B virus (anti HB. positive) in 1981 while 7% demonstrated antigenemia. The results demonstrate that: (1) alcohol abuse is common among adolescents and young adults in methadone maintenance therapy; (2) that it is associated with significant acute or chronic liver impairment; (3) exposure to HE virus is endemic in youthful former heroin addicts; and (4) the retention of alcohol‐abusing patients in methadone treatment and drug‐free follow‐up is as great as with non‐alcohol abusing patients.
Demonstration of Central Nervous System Tolerance to Ethanol in Mice: Consequent Effects on Smooth Muscle in Vitro
Authors: Dillon Margaret M. , Waters Donald H. , Triggle David J.
Published: February 2008

Mice were given ethanol (9 g/kg) or saline (57 ml/kg) daily in three divided doses for periods of 1 and 4 days to study the effects of such ethanol (ETOH) exposure on central nervous system (CNS) and peripheral smooth muscle (vasa deferentia) function. After 1 day, ETOH‐treated mice were functionally tolerant to the hypothermic (3 g/kg, intraperitoneal), but not to the hypnotic (3.25 g/kg, intraperitoneal) effect of ETOH. Functional tolerance to both CNS effects of ETOH was demonstrated in mice after the 4‐day ETOH exposure. Norepinephrine (NE) and high K+‐depolarizing solutions each elicited dose‐dependent contractions in the mouse vasa deferens preparation in vitro that consisted of a phasic and tonic component. The tonic components of the NE and K+ responses were more dependent upon extracellular Ca2+ (Ca2+ext) than the phasic components. Addition of ETOH (120 to 480 mM) or the Ca2+ channel‐antagonist nifedipine (1× 10+ to 3 × 10−‐7 m) to the preparation selectively inhibited the tonic component of the NE and K+ responses, suggesting that both agents acted to inhibit the responses by interfering with the translocation of Ca2+ext. Vasa deferentia isolated from ETOH‐treated mice did not exhibit altered reactivity to NE in the phasic or tonic comp nent of the response. The isolated smooth muscle from mice centrally tolerant to ETOH did not appear to be tolerant to the inhibitory effect of ETOH or cross‐tolerant to the inhibitory effect of nifedipine on stimulant‐induced contractions.
Alcohol and Sober Mood State in Female Social Drinkers
Authors: Bimbaum Isabel M. , Taylor Thomas H. , Parker Elizabeth S.
Published: February 2008

The goals of the present study were to measure the relationship between alcohol consumption in 93 female social drinkers and their cognitive functioning and mood in the sober state, and to investigate the possible causal effects of alcohol consumption on these variables. In the first test session, a limited relationship was seen between previous alcohol consumption and sober cognitive performance. A strong relationship was found between alcohol Consumption and self‐reported depression and anger in the sober state. Either a prolonged reduction in alcohol consumption or a prolonged maintenance of alcohol consumption was undertaken by random subsets of the original sample. In the second test session 6 weeks later, women who had been randomly selected to reduce their alcohol intake showed decreases in depression, anger, and mental confusion when they were sober, relative to women who maintained or increased their alcohol consumption over the same perlad of time. We found no changes in cognitive performance In these groups. We concluded that the simplest explanation of the findings is that relatively low levels of alcohol consumption produce wbstantial increases in depression and anger in the sober state in female social drinkers. The value of considering alcohol consumption as a continuous variable rather than a dichotomous variable with “safe” and “unsafe” zones was discussed.
Effect of Chronic Ethanol Ingestion on the Cyclic AMP System of the Upper Gastrointestinal Tract in the Rat
Authors: Seitz H. K. , Simon B. , Czygan P. , Veith S. , Kommerell B.
Published: February 2008

Chronic ethanol consumption significantly increases gastric adenyl‐ate cyclase (AC) activity (p < 0.05) without influencing low Km 3′,5′‐cyclic adenosine monophosphate (cAMP) phosphodiesterase (PD) activity in the rat. On the other hand, in the duodenum and upper part of the jejunum, chronic ethanol feeding leads to a significant decrease of adenyiate cyclase activity (p<0.02) and, again, does not affect low Km cAMP phosphodiesterase activity. In addition, the effect of various hormonal secretagoques on small intestinal adenylate cyclase activity was Investigated. Prostaglandin I2 and D2, as well as glucagon, do not stimulate AC at all. However, small intestinal adenylate cyclase exhibits a lower sensitivity to prostaglandin E2 and vasoactive intestinal peptide (VIP), and a lower efficacy to VIP after chronic ethanol consumption when compared to controls. The decrease of both basal and stimulated AC activity following ethanol ingestion in the upper small intestine may be due to membrane alterations and tissue damage caused by ethanol. The ethanol‐induced increase in gastric AC may be of relevance with respect to an increased acid secretion observed after alcohol administration.
Pattern of Alcohol Administration and Physical Dependence
Authors: PhD Bernard Le Bourhis. , Aufrère Gilles
Published: February 2008

The purpose of this work was to study the Influence of the pattern of alcohol administration on the intensity of withdrawal syndrome. Some rats were intoxicated by inhalation of ethanol vapor. The ethanol concentration in atmosphere was increased throughout the whole experiment in such a manner that the blood alcohol concentration (BAC) during the experiment increased as a linear function of time. When the area under BAC curve was varied by changing the duration of alcohol administration and keeping constant the slope of BAC increase, the intensity of withdrawal syndrome increased with the duration of alcohol intoxication. When the duration of alcohol administration and the slopes of the SAC curves were varied in such a manner that the area under the BAC curves was kept constant, the severity of the withdrawal syndrome increased with the slope of the SAC curves.
Inhibition of Prostaglandin Synthesis by Indomethacin Does Not Affect Alcohol Consumption in Inbred Mice
Authors: Anton Raymond F. , Randall Carrie L. , Williams Colleen K. , Hoffmeyer Gayle E.
Published: February 2008

The prostaglandin system has been implicated in mediating both the acute and chronic pharmacologic effects of alcohol. The effect of blockade of prostaglandin synthesis by indomethacin on genetically based alcohol preference in C57BL/6, C3H/He, and BALB/c mice was examined. Although strain typical alcohol preference patterns were observed, there was no effect of indomethacin on either naive or preestablished alcohol preference and consumption. Genetically transmitted alcohol preference may be a complex system in which prostaglandin synthesis does not play a part.
Physicians in Alcoholism: A Study of Current Status and Future Needs
Authors: Galanter Marc , Blume Sheila , Bissell LeClair
Published: February 2008

Members of the American Medical Society on Alcoholism were studied to shed light on medical manpower needs in the alcoholism field. Findings were compared to AMA and federal survey data for all American physicians. AMSA respondents were broadly distributed among specialties: primarily psychiatrists, internists, and family practitioners. They were evenly divided between office‐based and institutional practice, and most were on medical school faculties. Regarding alcoholism treatment, they generally agreed that Alcoholics Anonymous is necessary and that nonmedical counsellors are effective, although their altitudes on the etiology of alcoholism were divided. This sample of physicians in alcoholism, although not inclusive of all in the field, represents a diverse group, with differing clinical and educational needs.
Body Sway and Divided Attention Performance under the Influence of Alcohol: Dose‐Response Differences between Males and Females
Authors: Mills Kenneth C. , Bisgrove Eilene Z.
Published: February 2008

This study assessed women and men on a divided attention task, body sway, and subjective (self‐report) estimates of impairment across different doses of alcohol. Twelve females and 12 males (mean age of 20.4 years) were given placebo, low, and high doses of alcohol in random order across sessions. Each subject was tested 3 times during each session. The study controlled for recent drinking history by restricting participation to light drinkers who were matched on age and education. Alcohol doses were adjusted for body fat and equivalent blood alcohol concentrations (BACs) went attained in the two gender groups. The results indicated that women and men did not differ in their extent of cognitive impairment at placebo and low alcohol doses. However, women showed significantly more cognitive impairment than their male counterparts, at the high alcohol doses, even with equivalent BACs. The sway measure was influenced Only by BAC and not by the gender of the subject Sway observations were less sensitive and more variable than estimates of cognitive impairment The subjective impairment data indicated that female subjects were less sensitive than males to the effects of alcohol at both the low and high doses. Implications for future research on cognitive impairment are discussed.
Clinical Conditions and Concentrations of MOPEG in the Cerebrospinal Fluid and Urine of Male Alcoholic Patients during Withdrawal
Authors: Borg Stefan , Czarnecka Alexandra , Kvande Hans , Mossberg Dick , Sedvall Goran
Published: February 2008

The levels of 3‐methoxy‐4‐hydroxyphenylethyleneglycol (MOPEG), the major noradrenaline metabolite in the central nervous system, were analyzed in lumbar cerebrospinal fluid (CSF) and urine from 74 male alcohol addicts during acute withdrawal and after 1 week of abstinence. The values obtained were compared to those of 21 healthy male volunteers. Clinical conditions were rated on the Sampling days.

Concentrations of MOPEG were elevated during early withdrawal and the levels decreased during detoxication. This pattern was found in both the CSF and urine, irrespective of type of drug treatment during withdrawal. The clinical symptoms improved during withdrawal and, in the beginning, there were significant positive correlations between MOPEG levels in the CSF and sleeping problems, tremors, restlessness, visual hallucinations, and elevated muscle tension. Changes in MOPEG levels correlated to changes of mood. A significant correlation was also found between low MOPEG level and craving for alcohol. Few correlations were found between MOPEG levels in the urine and clinical symptoms.

The results indicate an elevated noradrenergic transmitter turnover rate in the early phase of alcohol withdrawal and a connection between noradrenaline metabolism and several clinical conditions during alcohol withdrawal.
Lymphocyte Subsets Studied with Monoclonal Antibodies in Liver Tissues of Patients with Alcoholic Liver Disease
Authors: Si Lusheng , Whiteside Theresa L. , Schade Robert R. , Thiel David Van
Published: February 2008

In order to determine the nature of T lymphocytes accumulating in hepatic tissues of patients with alcoholic liver disease, we phenotyped these cells in situ, using monoclonal antibodies to lymphocyte surface antigens and the avidin‐biotin‐peroxidase complex (ABC) technique. In portal areas of cirrhotic livers, a significant increase (p< 0.001) in T lymphocytes was observed as compared to livers showing only fatty changes and normal her tissues. The T cells accumulating in cirrhotic livers comprised T helper‐inducer (T4) and T suppressor‐cytotoxic (T8) subsets with the T4/T8 ratio of 1.4 f 0.5 (SD, n= 14). In contrast, the T lymphocytes in the cellular projections which extended into the parenchyma consisted mostly of suppressor‐cytotoxic cells. The relative enrichment in T8+ lymphocytes among the cells invading the parenchyma suggests that they may be important in the mediation of a cytotoxic injury of hepatocytes in advanced alcoholic liver disease and in regulating an immunologic challenge possibly initiated in response to alcoholic hyaline.
Alcohol‐Induced Changes in Lipids and Lipoproteins
Authors: Gandhi B. M. , Raina Nillima
Published: February 2008

Fasting plasma samples from 42 voluntary subjects of moderate to high socioeconomic status families and living in Delhi, taking 5–20 oz/week of alcohol regularly, and 42 normal subjects from comparable socioeconomic status with no history of intake of alcohol and no evidence of any known metabolic or coronary problems were analyzed for cholesterol and triglycerides and their levels in lipoprotein fractions, i.e., very low density lipoproteins (VLDL), low density lipoproteins (LDL), and high density lipoproteins (HDL). Free fatty acids, urea, uric acid, and glucose levels were also determined and dietary intake was calculated in the two groups.

Cholesterol and triglycerides in plasma, and VLDL and LDL fractions were found to be increased in the alcohol‐taking group even though their intake of alcohol was moderate. VLDL fraction formed 65 and 32% of total triglycerides and cholesterol, respectively. Sugar, uric acid, and free fatty acids (FFA) increased significantly in the alcohol‐taking group. Total energy intake was significantly higher in the alcohol‐taking group mainly from significant high intake of proteins and fats. Calculated on the basis of intake/day/kg of body weight the difference in intake of protein, fat, and carbohydrates was insignificant Regular intake of even small quantity of alcohol along with food rich in proteins and fats may induce elevation of high cholesterol‐containing lipoproteins, i.e., LDL and VLDL with increased hypertriglyceridemia, and these increased levels may constitute important coronary risk factors.
Effects of Chronic Ethanol Feeding on Sympathetic Innervated Organs: Temporal Sequence of Biochemical, Functional, and Trophic Changes
Authors: Rubio M. C. , Perec C. J. , Medina J. H. , Tiscomia O. M.
Published: February 2008

In noradrenergic nerves as well as In effector organs of the sympathetic nervous system, chronic ethanol feeding induced biochemical, functional, and trophic changes. The time sequence of modifications in the activities of tyrosine hydroxylase, phenylethanolamine‐N‐methyl transferase, monoamine oxidase, endogenous norepinephrine levels, as well as the neuronal uptake mechanism and secretory responses to norpinephrine in the submaxillary gland of the rat confirms that the effects of chronic ethanol administration are related to an increase in sympathetic tone.
Alcoholism, Anxiety Disorders, and Agoraphobia
Authors: Bowen R. C. , Cipywnyk D. , D'Arcy C. , Keegan D.
Published: February 2008

A group of 48 inpatient alcoholics were studied using the Schedule for Affectve Disorders and Schizophrenia–Life‐time Version (SADS‐L) and the Brief Standard Self‐rating for Phobic Patients. Approximately one‐quarter of the patients were diagnosed as suffering from agoraphobia and social and mixed phobias. Approximately 44% were diagnosed as suffering from anxiety disorders and 46% had suffered from an episode of major depression. Data from the self‐rating questionnaire were consistent with the diagnostic data. The alcoholics with phobias had experienced more severe dysphoric feelings than nonphobic alcoholics with other psychiatric disorders.
Effects of Elevated Female Sex Steroids on Ethanol and Acetaldehyde Metabolism in Humans
Authors: Jeavons Candace M. , Zeiner Arthur R.
Published: February 2008

Two groups (n = 20 each for pill and no pill groups) of young female social drinkers were tested with an acute ethanol dose (0.52 g/kg) as a 20% solution in water. Ethanol pharmacokinetics and acetaldehyde were repeatedly assayed from breath by a gas chromatograph. Cardiovascular indices were concurrently recorded. Groups did not differ on ethanol pharmacokinetics. However, the group on birth control pilts reached a significantly higher acetaldehyde concentration than did the group of normally cycling females not on birth control pills (3.26 ng/ml vs. 1.45 ng/ml). Further, the pill (P) group showed significantly greater vasodilation 20 mm postdrink as indexed by ear lobe plethysmography than did the no pill (NP) group (P = 160.3% vs. NP = 113.9%). Results are consistent with the interpretation that female sex steroids modulate aldehyde dehydrogenase function. Practical implications are that females with elevated steroids (either pregnant or on birth control pills) may be at greater risk for toxic effects 01 ethanol consumption.
Relationship of Endocrine Status on the Stimulatory Effect of Ethanol on Hepatic Very Low Density Lipoprotein Synthesis
Authors: Lakshmanan M. R. , Felver Michael E. , Ezekiel Mildred
Published: February 2008

The normal stimulatory effect of an acute oral dose of ethanol on hepatic very low density lipoprotein synthetic rate is abolished in thyroidectomized rats but not in adrenalectomized rats. This lack of stimulation by ethanol can be explained in part by the decreased rate of hepatic fatty acid esterification to neutral lipids in thyroidectomized animals.
Diagnostic Value of Serum Procollagen Peptide Measurements in Alcoholic Liver Disease
Authors: RiittaSavolainen Eeva‐ , Goldberg Burton , Leo Maria A. , Velez Maria , Leber Charles S.
Published: February 2008

Procollagen type I carboxyterminal and type III aminoterminal peptide concentrations were measured in sera of 60 patients with alcoholic and 14 with nonalcoholic liver disease to study whether these assays are useful as clinical tests to differentiate various stages of alcoholic liver injury. Both propeptides were markedly elevated in alcoholic hepatitis and cirrhosis: procollagen type III peptide in 90% and type I peptide in 60‐80% of these patients. Moderately increased values were found less frequently in patients with fatty liver. These tests did not differentiate patients with simple fatty liver from those with fatty liver and early fibrosis. There was a significant difference in serum procollagen type III peptide between fatty fiver and both alcoholic hepatitis and cirrhosis (p < 0.001), and in type I peptide between fatty liver and alcoholic hepatitis (p < 0.005). Although serum peptide values correlated with the degree of liver fibrosis, appreciable overlap of values was found between the various groups. The peptide concentrations also seemed to be related to the degree of hepatic inflammation, and the highest values were observed in a subgroup of patients with alcoholic hepatitis in whom numerous Mallory bodies were found. The data suggest that in alcoholic liver diseases, serum collagen propeptide determination may be useful in diagnosing severe alcoholic hepatitis.
Ethanol and Lipids
Authors: Lieber C. S. , Savolainen M.
Published: February 2008

The interaction of ethanol with lipid metabolism is complex. When ethanol is present, it becomes a preferred fuel for the liver and displaces fat as a source of energy. This favors fat accumulation. In addition, the altered redox state secondary to the oxidation of ethanol promotes lipogenesis, for instance, through enhanced formation of acylglycerols. The depressed oxidative capacity of the mitochondria injured by chronic alcohol feeding also contributes to the development of the fatty liver. Accumulation of fat acts as a stimulus for the secretion of lipoproteins and the development of hyperlipemia. Hyperlipemia may also be facilitated by the proliferation of the endoplasmic reticulum after chronic ethanol consumption and the associated increase of enzymes involved in the production of triglycerides and lipoproteins. The propensity to enhance lipoprotein secretion is offset, at least in part, by a decrease in microtubules and an impairment of the secretory capacity of the liver. The level of blood lipids depends on the balance between these two opposite changes: At the early stage of alcohol abuse, when liver damage is still small, hyperlipemia will prevail, whereas the opposite occurs with severe liver injury. When hyperlipemia occurs, it involves all lipoprotein classes, including high density lipoprotein (HDL). The latter have been suggested to be responsible for the lower incidence of coronary complications of moderate drinkers compared to teetotalers, but in fact, the subtype of HDL involved (HDL,) differs from the HDL2 subtype associated with protection.
Oxidation Phenotyping in Alcoholics with Liver Disease of Varying Severity
Authors: Lanthier Philippe L. , Reshef Ron , Shah Rashmikant R. , Oates Nicholas S. , Smith Robert L. , Morgan Marsha Y.
Published: February 2008

The propensity to develop alcoholic cirrhosis is probably, at least in part, genetically determined. A striking similarity exists histologically between pernexiline and alcohol‐related hepatitis and both are potentially precirrhotic lesions. Liver damage due to pernexiline is associated with impaired drug oxidation capacity which is genetically determined and tested by use of debrisoquine. Oxidation phenotyping might be used to predict susceptibility to pernexiline liver damage; it might also predict the potential to develop alcoholic cirrhosis. Oxidation phenotyping was therefore undertaken, using debrisoquine in 100 alcoholic patients, 30 of whom had only fatty liver despite prolonged alcohol abuse, while the remaining 70 had alcoholic hepatitis and/or cirrhosis. One hundred patients with nonalcoholic chronic liver disease served as controls. The number of patients with severely impaired drug oxidation capacity (poor metabolizer phenotype) was similar in the alcoholic group (8%) and the nonalcoholic control group (7%). In particular, the incidence of the poor metabolizer phenotype was similar in alcoholics with severe liver disease (10%) and in those with only fatty change (3%).

There appears to be no association between the susceptibility to develop alcoholic cirrhosis and drug oxidizing capacity.
A Reinvestigation of the Usefulness of Breath Analysis in the Determination of Blood Acetaldehyde Concentrations
Authors: Stowell Allan , Johnsen Jon , Aune Hakon , Vatne Karteif , Ripel Åse , Mørtand Jørq
Published: February 2008

Human volunteers were given ethanol (0.4 g/kg) either intravenous or per os. They were also given ethanol (0.2 g/kg) intravenous 4 hr after receiving a dose of 50 mg titrated calcium carbimide, an aldehyde dehydrogenase inhibitor. During the first hour after starting the administration of ethanol, ethanol and acetaldehyde concentrations were determined in expired air, blood from the right atrium, arterial blood, and venous blood. In the absence of calcium carbimide treatment, the respective maximal blood acetaldehyde concentrations were (range): 6‐30 μM (calculated from breath analysis using a Moodrbreath partition ratio of 190 for acetaldehyde); 0‐3.5 μM (right atrium blood); and 0 μM (arterial and venous blood). After calcium carbimide treatment, the maximal blood acetaldehyde concentrations were 10‐220 μM (calculated from concentrations in expired air), 38‐280 μM (right atrium), 31‐250 μM (arterial Wood), and 7‐186 μM (venous blood). With aldehyde dehydrogenase inhibition, a clear correlation existed between breath concentrations and blood concentrations. Without this inhibition, no such correlation was found. A clear arterio‐venous difference was seen for acetaldehyde concentrations whUe they were artificially elevated by calcium carbimide. Our study suggests that factors other than the equilibration of acetaldehyde between alveolar air and pulmonary blood are of great importance in determining the concentration of acetaldehyde in expired air.
Evidence for Impersistence in Young Male Alcoholics
Authors: Alterman Arthur I. , Tarter Ralph E. , Petrarulo Edward W. , Baughman Timothy G.
Published: February 2008

This investigation compared a group of 30‐year‐old male Veterans Administration inpatient alcoholics with an IQ, age, and education matched comparison group of nonpsychiatric VA outpatients or blue collar employees on three measures of persistence: Matching to Familiar Figures Test (MFFT), Retarded Rotation Test (RRT), and Mirror Tracing (MT). Alcoholics were found to make significantly more errors on the MFFT and MT tasks, but didn't differ significantly from nonalcoholics on the RRT. The alcoholics were also differentiated from the nonalcoholics on an overall index of persistence based on a combination of the three measures. The ramifications of the findings for understanding the etiology of the neuropsychological deficits manifested by alcoholics are discussed.
Drinking Norms Versus Drinking Behavior
Authors: Solomon Susan D. , Harford Thomas C.
Published: February 2008

Data from 1002 households indicated that contextual factors (group size, subsequent activity) and individual difference factors (sex, ‐extroversion, drinking frequency) differentially influenced consumption and normative ratings. These findings suggest that contextual cues serve as determinants of drinking norms and that drinking behavior reflects individual variation in sensitivity to these cues.
Ethanol Clearance in Nine Inbred Rat Strains
Authors: Erickson Carlton K.
Published: February 2008

The rate of ethanol disappearance was determined for each of eight inbred rat strains and the N/Nih line of heterogeneous rats. There are significant differences in ethanol elimination rates in the strains tested. Females have rates significantly different from those of males in five of the eight inbred strains and in the N/Nih line. Castration of males alters the rate of elimination only in the F344/N strain.
Studies on Tolerance Development in Inbred and Heterogeneous Stock National Institutes of Health Rats
Authors: Tabakoff Boris , Culp Steven G.
Published: February 2008

The rate of development of environment‐independent tolerance was assessed in seven inbred strains of rats, in randomly bred Sprague‐Dawley rats, and in the heterogeneous stock (HS) animals developed from the inbred strains. The results demonstrated significant differences in rates of tolerance development between the various groups of inbred animals. A relationship between the initial sensitivity of an animal to the incoordinating effects of ethanol and the rate of tolerance development was also demonstrated. Animals displaying the greatest initial sensitivity to ethanol were found to develop tolerance at a faster rate than those displaying greater resistance to the incoordinating effects of ethanol. The HS animals developed from the inbred strains were demonstrated to embody the full range of rates of tolerance development exemplified by the parental inbred strains.
Genetic Differences in the Effect of Ethanol on Plasma Corticosterone and Nonesterified Fatty Acid in Rats
Authors: Pohorecky L. A.
Published: February 2008

The influence of genotype on the responsiveness to ethanol in rodents was examined using biochemical measures. Nine different strains of rats were treated with saline or various doses of ethanol, and the changes in plasma corticosterone and of nonesterified free fatty acids were measured 1 hr later. It was found that the BUF/N strain of rats had the lowest response on both measures and also had the lowest blood ethanol levels. The most sensitive strains to ethanol were the ACI/N with respect to corticosterone, and WKY/N and M520/N with respect to nonesterified free fatty acids. The highest blood ethanol levels were seen in the MR/N and the WKY/N strains of rats.
Changes in (Na++K+)ATPase Activity and the Composition of Surface Carbohydrates in Erythrocyte Membranes in Alcoholics
Authors: Stibler Helena , Beaugé Francoise , Borg Stefan
Published: February 2008

(Na++K+)ATPase activity and sensitivity to the inhibitory effect of ethanol and noradrenaline in vitro as well as the concentrations of sialic acid, galactose, and hexosamine were determined in erythrocyte membranes in 20 healthy controls and in 20 alcoholic patients within 24 hr of withdrawal. Basal (Na++K+)ATPase activity, the sensitivity of the enzyme to inhibition by ethanol and noradrenaline added in vitro, and the concentrations of sialic acid and galactose were significantly reduced in the patients (p < 0.0005). All of these abnormalities were significantly correlated to each other as well as to the estimated dairy quantity of ethanol consumed. After enzymatic removal of terminal sialic acid and terminal and sialic acid‐bound β‐galactose, the (Na++K+)ATPase differences between the patients and the controls were eliminated. The results showed that the previously reported reduced inhibition of (Na++K+)ATPase by ethanol in the presence of noradrenaline in brain membranes in chronically ethanol‐fed animals is also found in erythrocyte membranes in alcoholic humans. Abnormal carbohydrate composition of glycoiipids and/or glycoproteins of the membrane surface appeared to be related to the (Na++K+)ATPase changes, possibly due to interference either with K+ transport or surface electrostatics or, directly or indirectly, with the conformation of (Na++K+)ATPase.
Diminished Blood Selenium Levels in Alcoholics
Authors: Dworkin Brad M. , Rosenthal William S. , Gordon Gary G. , Jankowski Rita H.
Published: February 2008

Plasma, whole blood, and red blood cell selenium levels were determined by spectrofluorometry in 30 patients with chronic heavy ethanol ingestion (group I) and 20 normal controls (group II). Nutritional and general medical evaluations were also performed. The mean plasma selenium level was 0.065 μg/ml ± 0.012 (so) for group I versus 0.100 ± 0.016 for group II (p < 0.0001). Whole blood levels were 0.076 μg/ml ± 0.011 versus 0.114 ± 0.015 (p < 0.0001), and red blood cell levels were 0.092 μg/ml ± 0.016 compared with 0.130 ± 0.025 (p < 0.0001), respectively. Mean triceps skin fold was 8.2 mm ± 3.5 for group I males versus 12.3 mm ± 5.0 (p < 0.005) for group II males but was not well correlated with whole blood selenium status (r = 0.33). Nutritional parameters of percentage of ideal body weight, midarm muscle circumference, serum albumin, and total lymphocyte count revealed no differences. Mildly elevated serum aspartate aminotransferase and/or alkaline phosphatase values occurred in 53% of alcoholics, but selenium levels in these patients were no different from those with normal liver tests. We conclude that depressed blood selenium levels occur frequently in patients with chronic heavy ethanol ingestion even in the absence of overt malnutrition. Since selenium deficiency can produce a spectrum of organ injury which resembles that associated with chronic alcoholism, the relationship of selenium deficiency to alcohol‐induced organ injury deserves further study.