bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Acute and Chronic Ethanol Administration on Rat Liver α 2,6‐Sialyltransferase Activity Responsible for Sialylation of Serum Transferrin
Authors: Malagolini Nadia , Dall'Olio Fabio , Serafini‐Cessi Franca , Cessi Carlo
Published: April 2006

The effect of a single administration and a 6‐week treatment with ethanol on rat liver sialyltransferase activity towards asialoglycoproteins and N‐acetyllactosamine (Galβ91,4GlcNAc) was studied. Since only the cα2,6‐sialyltransferase is involved in the in vivo sialylation of transferrin, GalβS1,4GlcNAc was chosen as an acceptor and α2,6‐sialyl‐N‐acetyllactosamine was separated from the corresponding α2,3‐sialyl isomer present in the sialyltransferase reaction mixture by high‐performance liquid chromatography. After a single ethanol administration there was a low (about 20%) but significant (p < 0.005) reduction of sialyltransferase activity towards asialotransferrin as well as a reduced α2,6‐sialyltransferase activity towards N‐acetyllactosamine. An opposite result was found in the chronically ethanol‐treated rats: in these animals either the total or α2,6‐sialyl‐transferase activity was slightly higher than in control animals. Blood ethanol concentration was significantly high (3.3 ±1.2 mg/ml) only in the acute‐treated animals, suggesting that the accumulation in the body of ethanol and/or its metabolites induces a reduction of liver α2,6‐sialyltransferase activity responsible for the transferrin sialylation. Current results are consistent with the finding (Stibler H, Hultcrantz R: Alcohol Clin Exp Res 11:468–473, 1987) that an enhanced level of hyposialylated transferrin isoforms is a marker of present but not previous alcohol abuse.
MRI Study of Brain Changes with Short‐Term Abstinence from Alcohol
Authors: Zipursky Robert B. , Lim Kelvin O. , Pfefferbaum Adolf
Published: April 2006

Magnetic resonance brain scans were obtained from 10 chronic alcoholics within 2 weeks of alcohol withdrawal, and 19 to 28 days later. Age‐matched control subjects were scanned at comparable intervals. At the initial scan, the alcoholics had larger lateral ventricles than the controls; at the second scan, their ventricles were significantly smaller than at the first scan. Among the controls, there was no mean change in the size of the lateral ventricles between the first and second scan. This study demonstrates reversibility in ventricular enlargement with short‐term abstinence from alcohol. The role of rehydration in this process and the possibility of further changes with continued abstinence remain to be tested.
A Conflict Procedure Not Requiring Deprivation: Evidence That Chronic Ethanol Treatment Induces Tolerance to the Anticonflict Action of Ethanol and Chlordiazepoxide
Authors: Criswell Hugh E. , Breese George R.
Published: April 2006

A conflict task that does not require food or water deprivation is described. Drugs with known anticonflict action including chlordiazepoxide, methysergide, ethanol, and TRH were active In this test while amphetamine, buspirone, and morphine were not Because this procedure did not require food or water deprivation, the effect of chronic ethanol administered in a liquid diet on the anticonflict actions of ethanol and chlordiazepoxide could be examined. Seven or 12 days of chronic ethanol treatment resulted in tolerance to the acute anti‐conflict action of ethanol whereas 3 days of treatment did not Tolerance was not observed to a dose of ethanol administered 3 hr after a previous ethanol treatment Following a chronic ethanol liquid diet, cross‐tolerance to the anticonflict action of chloridazepoxide was observed. This latter observation is consistent with the view that ethanol Influences a neural mechanism associated with benzodiazepine function. The importance of tolerance to the anticonflict action of ethanol is discussed.
More Rapid Elimination of Alcohol in Women as Compared to Their Male Siblings
Authors: Mishra Lopa , Sharma Savitri , Potter James J. , Mezey Esteban
Published: April 2006

Sex differences in rates of ethanol elimination were investigated in natural siblings to reduce genetic variability as compared to subjects chosen at random. Ethanol was infused intravenously in a dose of 0.6 g/kg of body weight over 45 to 60 min and serial blood samples obtained for 5 hr. The mean rate of ethanol elimination was higher in seven women, not different in one, and lower in one compared with their male siblings. The mean rate of ethanol elimination for all nine women was higher at 1.93 ± 0.12 as compared with the value of 1.69 ± 0.17 mmoles/kg body weight/hr in the men (p < 0.05). Higher rates of ethanol metabolism in women as compared to men may be important in the increased susceptibility of women to liver injury caused by alcohol consumption.
Human Brain Glyceraldehyde‐3‐Phosphate Dehydrogenase, Succinic Semialdehyde Dehydrogenase and Aldehyde Dehydrogenase Isozymes: Substrate Specificity and Sensitivity to Disulfiram
Authors: Ryzlak Maria T. , Pietruszko Regina
Published: April 2006

Several enzymes active in the presence of NAD with acetaldehyde and propionaldehyde have been purified from human brain and characterized. The enzymes have been identified as aldehyde dehydrogenase (EC 1.2.1.3), NAD‐linked succinic semialdehyde dehydrogenase (EC 1.2.1.24), and glyceraldehyde‐3–phosphate dehydrogenase (EC 1.2.1.12). Glyceraldehyde‐3–phosphate dehydrogenase is extremely heterogeneous with some isozymes active with acetaldehyde, others inactive. The cytoplasmic enzyme, which is the classical glyceraldehyde‐3–phosphate dehydrogenase, is inactive with acetaldehyde as substrate; the isozymes that are active with short chain aliphatic aldehydes are localized in the mitochondrial fraction. Properties of glyceraldehyde‐3–phosphate dehydrogenase isozymes with respect to short chain aliphatic aldehydes and inhibition by disulfiram are described. Their Km values for acetaldehyde range from 300 to 2000 MM. All glyceraldehyde‐3–phosphate dehydrogenases that are active with acetaldehyde are easily inactivated by low concentrations of disulfiram. In all cases activity regain can be obtained with 2–mercaptoethanol; in the case of two glyceralde‐hyde‐3–phosphate isozymes (E8.5 and 9.0), activity can also be regained with cysteine and with glutathione; activity of E6.6 and E6.8 glyceraldehyde‐3–phosphate dehydrogenases could not be regained with 33 MM cysteine or glutathione. Succinic semialdehyde dehydrogenase and aldehyde dehydrogenase (EC 1.2.1.3) were also inhibited by disulfiram; their activity could be regained with 2–mercaptoethanol but not with 33 MM cysteine or glutathione. Comparison of human brain succinic semialdehyde dehydrogenase and aldehyde dehydrogenase with glyceraldehyde‐3–phosphate dehydrogenase shows that the activity with short chain aldehydes is not unique to aldehyde dehydrogenase; neither is sensitivity to disulfiram; activity with 3,4–dihydroxyphenylacetaldehyde appears to be a unique property of aldehyde dehydrogenase (EC 1.2.1.3).
In Vitro Effect of Acetaldehyde on Cell‐Mediated Cytotoxicity by Murine Spleen Cells
Authors: Walia Amrik S. , Pruitt Kenneth M. , Dillehay Dirck L. , Marshall G. M. , Lamon E. W.
Published: April 2006

The effects of acetaldehyde in vitro on the lytic capacity of murine spleen cells have been evaluated in three systems: antibody‐dependent cell‐mediated cytotoxicity (ADCC), natural killer (NK) activity, and alloimmune cytotoxic T lymphocyte (CTL) activity. Acetaldehyde had a biphasic effect on ADCC. Concentrations less than 1 mM acetaldehyde potentiated ADCC. Concentrations >1 mil produced a progressive decrease in lysis. The inhibitory effects were at the effector cell level and were partially irreversible. Preincubation experiments showed that inhibition of ADCC was both concentration and time‐dependent. Preincubation of the spleen cells for short periods of time produced potentiated lysis by concentrations of acetaldehyde up to 10 mM. However, potentiation of lysis in preincubation and short term (4h) lytic assay experiments was more variable than longer term (18h) experiments in which the acetaldehyde was not removed by washing. NK activity and alloimmune CTL‐mediated lysis were also inhibited by acetaldehyde. Concentrations of acetaldehyde up to 20 mM did not significantly decrease lymphocyte viability as determined by trypan blue exclusion. Acetaldehyde was lost from the reaction mixtures by first order kinetics with a rate constant of 0.5/hr. Thus, the final concentrations were 64–99.99% lower than the starting amounts.
The Structure of Psychological Defense Mechanisms in Women as a Function of Alcohol Intoxication
Authors: Gustafson R. , Källmén H.
Published: April 2006

The present experiment tested whether moderate alcohol intoxication influences the relative strength of different psychoanalytic defense mechanisms and whether the overall level of defense activity is changed. Thirty‐six women were randomly assigned to either an alcohol, a placebo, or a control group. The alcohol dose was 1.0 ml of 100% alcohol/kg body weight. Subjects were tested with the Defense Mechanism Test (DMT), which gives a valid measure of both elaborate or late and primitive or early defense mechanisms. Results indicated no significant effects of alcohol intoxication on any aspect of the defense system. This was taken as supportive of the psychoanalytic notion in respect of the stability of the defense system. Possible complications were discussed.
A Scheme for Determining the Prevalence of Alcoholism in Hospitalized Patients
Authors: Baird Macaran A. , Burge Sandra K. , Grant William D.
Published: April 2006

As a part of an on‐going effort to assess the prevalence of alcoholism among hospitalized patients, a structured technique was devised to document the prevalence of alcoholism in a large teaching hospital. A system of inpatient chart audit classification was developed to assess direct evidence of patient alcoholism. In addition, the reported prevalence of alcoholism as a discharge diagnosis was determined. An assessment of the degree of alcoholism was used to classify patients into severity levels. A determination was made of the relationship of hospital chart data classification level to other medical problems or treatments directly addressed by the physicians) that would indicate that the alcohol abuse, if present, was considered. A retrospective chart audit was conducted for 809 consecutive adult admissions to a 350‐bed urban university teaching hospital using a specific classification scheme for determining evidence of alcoholism. This technique revealed a reported prevalence of alcoholism in 4.3% of all nonobstetric admissions to this university hospital. However, a chart review technique using specific criteria for the diagnosis of probable alcoholism raised the estimated prevalence to 15.9%. When the chart contained a primary diagnosis of alcoholism, physicians' responses reflected treatment plans that addressed acute management of alcohol related medical complications but often did not document efforts to assist the patient with the underlying alcoholism/substance abuse.
Alcohol and Drug Abuse in Treated Alcoholics: A Comparison of Men and Women
Authors: Ross Helen E.
Published: April 2006

A survey of 229 male patients and 198 female patients who met lifetime DSM‐III criteria for alcohol abuse or dependence was carried out in Toronto, Canada. The patients were evaluated with the National Institute of Mental Health Diagnostic Interview Schedule and other substance abuse rating scales. The prevalence of individual alcohol and drug symptoms, the patterns of abuse, and the prevalence of drug disorders were compared in the two sexes. The study patients were younger than previous treatment samples and were more likely to have other drug disorders. While the overall prevalence of drug disorders was similar in male and female alcoholics, women were more likely to abuse sedatives and minor tranquilizers while men were more prone to the abuse of cannabis and tobacco. Men continue to be more likely to have social and occupational problems resulting from alcohol abuse, to start abusing alcohol earlier in their lives, to have been abusing for longer, and to report higher quantity and frequency of alcohol consumption. With one or two exceptions, the sexes do not differ on other indicators of pathologic use, withdrawal or tolerance, medical sequelae or treatment history. While men have significantly more alcohol problems than women, as measured by the DIS and the MAST, these differences disappear when length of alcohol abuse history, antisocial personality disorder and employment status are controlled for. Similarly, when these variables are controlled for, women exhibit more symptoms of alcohol dependence as measured by the ADS. Women alcoholics come into treatment earlier in their alcoholic careers.
Event‐Related Potential Characteristics in Children of Alcoholics from High Density Families
Authors: Hill Shirley Y. , Steinhauer Stuart , Park Jennifer , Zubin Joseph
Published: April 2006

Sons and daughters (ages 8–14) of male alcoholics without psychiatric problems were compared with sons and daughters of controls employing two auditory paradigms to elicit event‐related potentials (ERPs). All of the children of alcoholics were from high density families (each father had an average of 3.7 first and second‐degree relatives meeting criteria for alcoholism). Subjects were presented with high‐ and low‐pitched tones with global probabilities of 25% and 75% of total trials, respectively. Subjects were instructed to count silently the number of “high’tones (rare targets) but not the number of “low’tones (non‐targets) and report the number heard. In a second auditory paradigm (Choice Reaction task), subjects were asked to perform a different motor response to each high or low tone. The amplitude of the P300 component was influenced significantly by event probability (decreased amplitudes were associated with increased event probability). A greater rate of decrease in P300 amplitude occurred among the high risk children as event probability increased. In addition, greater negativity beginning at approximately N250 was observed for both tasks at the frontal electrode for the high risk children as compared to controls. This enhanced frontal negativity is interpreted in terms of a maturational lag hypothesis.
Alterations in Gait Following Ethanol Exposure During the Brain Growth Spurt in Rats
Authors: Meyer Linda S. , Kotch Lori E. , Riley Edward P.
Published: April 2006

Walking patterns were assessed in rats that had been exposed to alcohol neonatally during a period encompassing the brain growth spurt. Rat pups were exposed via an artificial rearing technique to either a 2.50% (w/v) or 2.15% (w/v) EtOH‐milk formula on Days 26‐32 postconception. An artificially reared control group and a suckle‐control group were also included in the experiment. Gait patterns were assessed in animals from each of the neonatal treatment groups at 43, 67, and 87 days postconception. No differences in gait patterns were evident on Day 43 postconception; however, on Days 67 and 87 animals exposed to alcohol during the neonatal period displayed an abnormal gait. These animals had a shortened stride length and an increased angle of placement of the hindfeet relative to artificially reared and suckle‐control animals. The altered gait pattern may be the result of alcohol‐induced hippocampal and cerebellar damage during the brain growth spurt.
Ethanol Self‐Administration in Males with and without an Alcoholic First‐Degree Relative
Authors: de Wit H. , McCracken S. G.
Published: April 2006

The reinforcing and subjective effects of a low dose of ethanol (ETH; 0.5 g/kg) were investigated in normal males with or without an alcoholic first‐degree relative. Reinforcing effects were measured using a double‐blind preference procedure comparing ETH to placebo (PLC), and subjective effects were assessed using standardized self‐report questionnaires. Subjects with a positive family history of alcoholism (FHP) did not differ from subjects without alcoholic relatives (FHN) either in frequency of choice of ETH over PLC (about 60% of occasions) or in the total dose self‐administered (about 0.9 g/kg per session). The two groups also did not differ on most measures of acute ETH effects (e.g., mood‐altering effects, liking ratings, behavioral changes, or blood ETH levels). The FHP subjects reported a slightly faster onset of “feeling any drug effects’and “high’after ETH than the FHN group. The FHP group also scored higher than the FHN group on several scales indicative of dysphoric mood, regardless of drug administration. Thus under these conditions male social drinkers with or without a family history of alcoholism did not differ either in preference for ETH or in their subjective responses to the drug.
Ethanol‐Induced Esophageal Motor Disorder: Development Of An Animal Model
Authors: Keshavarzian A. , Rizk G. , Urban G. , Willson C.
Published: April 2006

Abnormal esophageal motility has been reported in alcoholics. This includes abnormally high esophageal contraction amplitudes (ECA) and elevated lower esophageal sphincter pressures (LESP). However, an animal model is lacking for evaluating the underlying mechanisms. To develop such a model of ethanol‐induced esophageal motor dysfunction, esophageal manometry was done in control, chronically intoxicated, and withdrawing cats. Ethanol was administered for at least 30 days via gastrostomy tube and blood alcohol levels, typically 300 mg/dl, were adjusted to maintain inebriation. LESP and upper (striated muscle) and lower (smooth muscle) ECA were elevated in male withdrawing cats. In intoxicated cats only upper ECA was elevated. Surprisingly, LESP and ECA were not significantly affected in females. Duration of ECA was prolonged in both male and female intoxicated cats. These findings indicate that: (1) similar to withdrawing men, ECA and LESP are elevated in withdrawing male cats; (2) ethanol‐treated cats are an appropriate model for studying the mechanism of ethanol effects on esophageal motor function; (3) gender has a significant role in influencing the effects of alcohol.
Comparative Pharmacokinetics of Ethanol in Inbred Strains of Mice Using Doses Based on Total Body Water
Authors: Faulkner Thomas P. , Cantleberry Shelly B. , Watts Val J. , Hussain Ajaz S.
Published: April 2006

The mean total body water was determined by desiccation in DBA/2J, CBA/J, and C57BL/6J mice to be 60.6, 65.6, and 68.6 percent of body weight, respectively. The pharmacokinetics of ethanol was subsequently studied in mice of these strains given an intraperitoneal dose of 116 mmoles/l of total body water based on the desiccation study. This dose was equivalent to 70, 76, and 80 mmoles/kg in the DBA/2J, CBA/J, and C57BL/6J strains, respectively. The zero time concentrations were nearly identical between strains; therefore volume of distribution (VD) estimates based on mmole/kg doses reflected interstrain differences in total body water. The apparent zero order elimination rate was significantly greater in the DBA/2J strain versus the other two strains using this regimen. Interstrain differences in ethanol sleep time paralleled the differences in anesthetic sensitivity evidenced by blood concentrations at the time of regaining the righting reflex. The results demonstrate the importance of considering differences in total body water and hence ethanol VD when comparing the effects of ethanol in inbred mouse strains.
The Effects of Ethanol Consumption on the Expression of Immunity to Trichinella spiralis in Rats
Authors: Steven William M. , Kumar Shantha N. , Stewart George L. , Seelig Leonard L.
Published: April 2006

The effects of ethanol ingestion on immune responses of female rats against Trichinella spiralis (T. spiralis) infections were investigated. Female rats were pair‐fed either ethanol‐containing or isocaloric control liquid diets for 68 days, during which time they underwnt one pregnancy cycle. For some studies, animals were fed ethanol diets for 68 days beginning prior to pregnancy and continuing through lactation and involution. They were infected on Day 7 of involution with 1000 L1 larvae of T.spiralis and tested for a primary rejection response 10 days later. To test for a secondary immune response, rats were infected with T. spiralis, placed on ethanol‐containing liquid diet 15 days later, and after 68 days on diets, challenged with 1000 T. spiralis larvae and killed 3 days later. For primary immunized studies, ethanol‐treated animals demonstrated significantly lower levels of anti‐T. spiralis serum antibodies in ELISA, reduced rates of H3 thymidine incorporation by lymph node cells stimulated with T. spiralis antigen and significantly higher numbers of intestinal worm burdens (decreased immunity) compared with pair‐fed controls. For animals sensitized to T. spiralis prior to pregnancy and given a secondary challenge during involution, no differences were found between ethanol and pair‐fed animals in their ability to reject their worm burdens or in anti‐T. spiralis serum antibody levels; however, ethanol‐treated animals showed reduced rates of thymidine incorporation by lymph node cells when stimulated with T. spiralis antigen. These results suggest that ethanol consumed prior to immunization can inhibit immune responses, including antibody production, to T. spiralis during a primary immune response; however, when made immune prior to ethanol administration, it has less of an effect on a secondary immune challenge.
Differential Regulation of Anterior Pituitary Corticotrope Function is Observed in Vivo but not in Vitro in Two Lines of Ethanol‐Sensitive Mice
Authors: Wand Gary S.
Published: April 2006

Anterior pituitary corticotrope function was analyzed in the long sleep (LS) and short sleep (SS) lines of mice selectively bred for differences in sensitivity to ethanol. In vivo challenge with acute ethanol or CRH administration or the stress of novel handling resulted in a more pronounced increase in serum corticosterone levels in LS mice compared with SS mice. Likewise, in vivo administration of ethanol resulted in 3‐fold higher levels of anterior pituitary pro‐ACTH/endorphin mRNA in LS mice compared with SS mice. However, this differential regulation of the HPA axis during in vivo analysis was not observed during in vitro studies of anterior pituitary corticotrope function. Primary cultures of LS and SS anterior pituicytes responded appropriately but equivalently to a variety of secretagogues known to stimulate anterior pituitary ACTH secretion. These secretagogues included CRH (10 nm), dibutyryl‐cAMP (1 mm), vasopressin (100 nm), and phorbol 12‐myristate 13‐acetate (10 nm). Ethanol had no direct stimulatory effect on pituitary ACTH secretion. Quantitation of anterior pituitary corticotrope peptide biosynthesis was determined by immunoprecipitation and sodium dodecyl sulfate‐polyacrylamide gel electrophoresis of extracts from [35S]methionine‐labeled anterior pituitary explants and from [35S]methionine‐labeled primary cultures of anterior pituitary cells. LS mice pro‐ACTH/endorphin biosynthesis in pituitary explants was 2‐fold greater than pro‐ACTH/endorphin biosynthesis in SS mice pituitary explants. However, in culture, isolated from hypothalamic and adrenal factors, the LS anterior pituitary pro‐ACTH/endorphin biosynthetic rate became eguivalent to the SS anterior pituitary pro‐ACTH/endorphin biosynthetic rate. The results suggest that the differential regulation of LS and SS anterior pituitary corticotropes observed in vivo is not due to genetic differences in LS and SS anterior pituitary corticotrope function.
Problems Associated with Average Alcohol Consumption and Frequency of Intoxication in a Medical Population
Authors: Kranzler Henry R. , Babor Thomas F. , Lauerman Richard J.
Published: April 2006

The relationship between patterns of alcohol consumption and adverse consequences of drinking was examined in a cross‐sectional study of hospital patients. Regular drinking that exceeds 40 g per day by males and 25 g per day by females was found to increase significantly the risk of a variety of alcohol‐related medical and psychosocial problems. Similarly, frequent consumption of six or more drinks per occasion significantly increased the risk of problems for both men and women. Among males elevated average daily consumption contributed more to alcohol‐related problems than frequency of intoxication, while the opposite was true for females. These results indicate that the frequency and amount of alcohol consumption are important risk factors for both nonalcoholics and alcoholics, and that measures of drinking pattern may be useful for screening purposes.
Effects of Arachidonic Acid on Hepatic Lipids in Ethanol‐Fed Rats
Authors: Stern Zev , Korsten Mark A. , De Carli Leonore M. , Lieber Charles S.
Published: April 2006

The effects of arachidonic acid supplementation on rats fed ethanol employing an ad libitum schedule have been reported to be different from those observed when rats are fed in more limiting, matched fashion. To reexamine this issue, rats were fed unrestricted amounts of a diet in which 36% of the energy was provided by either ethanol or isocaloric amounts of carbohydrate. In half the animals, 7% of fat consisted of arachidonic acid. Despite earlier reports to the contrary, arachidonic acid had no effect on weight gain and did not attenuate the ethanol‐induced fatty liver. Arachidonate supplementation tended to increase hepatic total lipids and triacylglycerols, and to potentiate the ethanol‐induced elevation of cholesterol esters. Our present results are consistent with those previously reported using pair‐feeding techniques in which dietary intakes are somewhat limited. Thus, regardless of the feeding technique employed, relative arachidonic deficiency cannot be invoked to explain the lipid accumulation observed after chronic ethanol consumption.
Genetically Determined Alcohol Preference and Cyclic AMP Binding Proteins in Mouse Brain
Authors: Beeker Kelly R. , Lee Renee C. , Phung Hanh M. , Smith Carlton P. , Pennington Sam N.
Published: April 2006

Free‐choice consumption of alcohol by mice with differing phenotypic alcohol preferences caused uniformly large decreases in brain cyclic AMP‐dependent protein kinase activity toward an exogenous substrate (histone 2b) but the effect of alcohol on brain cyclic AMP binding activity was strain‐specific. Furthermore, particulate kinase phosphorylating activity toward an endogenous protein (kinase regulatory subunit, RII) was altered by alcohol consumption in a strain‐specific manner. The changes in cyclic AMP binding and phosphorylating activity appeared to result from phenotypic differences in the brain's response to alcohol. Thus, low preference animals were sensitive to alcohol and showed a large decrease in cyclic AMP binding and an increase in phosphorylation of regulatory subunit in response to alcohol. In contrast, high preference strain had only a small decrease in cyclic AMP binding and a decrease in phosphorylation, even though these animals consumed a significantly larger dose of alcohol. These data suggest that changes in cyclic AMP binding and/or phosphorylation of kinase regulatory subunit may be phenotypic markers of alcohol preference in inbred mice.
Protein Synthesis in Bone and Skin of the Rat Are Inhibited by Ethanol: Implications for Whole Body Metabolism
Authors: Preedy Victor R. , Marway Jaspaul S. , Salisbury Jonathan R. , Peters Timothy J.
Published: April 2006

The acute effects of ethanol (75 mmol/kg body weight, intraperitoneal) on rates of protein synthesis in bone (tibia) and skin of young (approximately 100 g body weight) laboratory rats was investigated. Plasma ethanol levels were raised to approximately 40 mmol/liter. At 2.5 hr, rates of protein synthesis were measured with a flooding dose of L‐[4‐3H]phenylalanine. In bone the protein‐bound specific radioactivities, fractional synthesis rates, and synthesis rates relative to RNA and DNA were significantly reduced by approximately 30%. In skin these variables similarly decreased in response to ethanol treatment, by approximately 25%.

The reduction in absolute rates of protein synthesis in bone (Δ, 0.7 g protein/day/kg body weight) and skin (Δ, 3.4 g protein/day/kg body weight) were comparable to the reductions in liver and skeletal muscle in response to acute ethanol. As bone and skin contribute to a quarter of whole body protein synthesis, it was concluded that these observations may have important implications for whole body protein homeostasis.
Interaction of Ethanol with Enflurane Metabolism and Toxicity: Role of P450IIE1
Authors: Tsutsumi Rika , Leo Maria Anna , Kim Cho‐il , Tsutsumi Mikihiro , Lasker Jerome , Lowe Nancy , Lieber Charles S.
Published: April 2006

Administration of enflurane (EF), a widely‐used anesthetic agent, sooetimes results in occult liver injury. As hepatic cytochromes P450 oxidize EF to a reactive intermediate, we assessed whether one such microsomal enzyme, ethanol‐inducible P450IIE1, plays an obligatory role in EF metabolic activation and hepatotoxicity. Liver microsomes from rats fed ethanol (36% of total calories for 14 days) oxidized 1 mm EF (measured by its defluorination) at rates nearly 10‐fold greater than those from control rats, reflecting the markedly enhanced content of immunoreactive microsomal P450IIE1 in the former animals. P450IIE1 involvement in hepatic EF oxidation was further suggested by the pronounced inhibition of microsomal defluorination noted with P450IIE1 antibodies and with ethanol, a specific substrate for this enzyme. EF administration to rats treated chronically with ethanol caused significant elevations in plasma levels of aspartate and alanine aminotransferases and glutamate dehydrogenase, indicative of hepatic injury, whereas concurrent treatment of naive rats with EF and ethanol failed to produce the same effect. Our results imply that ethanol‐inducible P450IIE1 is the primary catalyst of hepatic EF bioactivation and that the increased bioactivation occurring in vivo secondary to chronic ethanol consumption is attendant with an increased incidence of EF hepatotoxicity.
Body Composition in Detoxified Alcoholics
Authors: York James L. , Pendergast David E.
Published: April 2006

Body composition was evaluated in healthy detoxified alcoholics (aged 20–39) and lifestyle controls, with the expectation that prolonged, excessive consumption of alcohol may bring about nutritional or toxicologic alterations in the relationship between body fat and lean body mass. Body fat was assessed by measurements of skinfold thickness and by means of bioelectric impedance methodology. No noteworthy differences were observed between alcoholics and controls with regard to the relationship between lean body mass and body fat or in the relationship between extracellular and intracellular water. It would appear that 15–20 years of heavy alcohol consumption does not necessarily alter body composition in healthy, young alcoholics.
Ad Libitum Alcohol Ingestion Does Not Induce Renal IgA Deposition in Mice
Authors: Smith Suzanne Meleg , Hoy Wendy E
Published: April 2006

This study investigated the induction of alcohol abuse related IgA glomerulonephritis in mice, a disease we have previously described in humans and in rats with noncirrhotic alcoholic liver disease. A commercial liquid diet was fed ad libitum to 115 mice from three strains: C57BL/6J, BALB/cJ, and C3H/HeJ. Animals were divided into two groups: 60 received 30% of their caloric intake as ethanol—alcoholized; and 55 were fed the same calorie count in the form of glucose—controls. Mice were killed at weekly intervals after 4 to 10 weeks of liquid diet ingestion. No diagnostic renal pathology was observed.
Acute Alcohol Infusion Does Not Alter Plasma Gonadotropins or Prolactin in Ovariectomized Rats
Authors: Subramanian Marappa G. , Savoy‐Moore Ruth T. , Bergeski Barbara A. , Kruger Michael L. , Abel Ernest L.
Published: April 2006

We examined the effects of acute alcohol on basal plasma FSH, LH, and prolactin in ovariectomized rats. Alcohol infusion and blood sampling were done via an indwelling atrial catheter. Blood samples for alcohol and hormone determinations were collected before, and 5 to 120 min after completion of saline (control) or alcohol in saline (experimental) infusion. Plasma follicle‐stimulating hormone, luteinizing hormone, and prolactin were not altered during the 2‐hr period. Peak blood alcohol concentrations achieved following 1.0‐ and 2.0‐ g/kg body weight of alcohol doses were approximately equal to, and twice, the legal human intoxication levels, respectively. Alcohol clearance rates from blood for the two groups were: 130 ± 3 mg/kg/hr for the 1.0‐g/kg body weight group and 151 ± 3 mg/kg/hr for the 2.0‐g/kg body weight group. These results show that acute alcohol does not affect basal gonadotropins and prolactin secretion in ovariectomized rats.
Further Characterization of LSXSS Recombinant Inbred Strains of Mice: Activating and Hypothermic Effects of Ethanol
Authors: Erwin V. Gene , Jones Byron C. , Radcliffe Richard
Published: April 2006

Lines of mice selected for differential initial sensitivity to the anesthetic effects of ethanol also differ in their locomotor responses to lower doses of ethanol. Sixteen recombinant inbred strains of mice derived from long‐sleep (LS) and short‐sleep (SS) selected lines as well as inbred LS and SS mice were used in a genetic correlational study to investigate possible associations between high‐dose and low‐dose indices of initial sensitivity to ethanol. Measurements of high‐dose (4.1 g/kg) effects of ethanol were hypothermia, sleep time, and blood ethanol content at regaining of righting response, and the index of low‐dose (1.875 g/kg) sensitivity was distance traveled during a 5‐min period immediately following intraperitoneal injection with ethanol. The results indicated wide genetic variation in hypothermia and ethanol‐induced locomotor activation in a manner consistent with polygenic influence. Furthermore, correlations between low‐dose locomotor activity and hypnotic dose effects tended to be low and nonsignificant, indicating independence of inherited mechanisms underlying high‐ and low‐dose ethanol sensitivity.
Alcohol Intoxication Blunts Sympatho‐Adrenal Activation Following Brain Injury
Authors: Woolf Paul D. , Cox Christopher , Kelly Mary , McDonald Joseph V. , Hamill Robert W.
Published: April 2006

In 46 patients experiencing traumatic brain injury, we studied the interactions of alcohol intoxication and severity of neurologic dysfunction on the resulting sympathetic nervous system activation. Sixty percent of the variation in norepinephrine (p < 0.0001) and more than 50% of the variation in epinephrine (p < 0.0001) were due to the initial ethanol concentrations and extent of brain injury assessed by the admission Glasgow Coma Score (GCS). As brain function deteriorated plasma cathecholamines rose (p < 0.0001), but ethanol qualitatively and quantitatively modified this observation. The magnitude of the sympathetic response to worsening neurologic function was progressively diminished in association with increasing ethanol levels, i.e., the inverse relationship of GCS values with both norepinephrine and epinephrine was flattened. In comatose patients (GCS < B) increasing ethanol levels was associated with progressively decreasing norepinephrine and epinephrine responses (p < 0.04), such that catecholamines were reduced by 80 to 90% at ethanol concentrations approaching 400 mg/dl (87.0 mmol/l). However, the impact of ethanol on the degree of sympathetic nervous system activation depended upon the degree of injury; the apparent ethanol suppression was greatest in patients with the most severe neurologic dysfunction (GCS 3 or 4), but it diminished as neurologic function improved.

We conclude that the presence of alcohol appears to modify the rise in catecholamine levels following traumatic brain injury in a dose‐dependent manner and alters the relationship between neurologic dysfunction and SNS activation. These alterations may have profound effects on patient morbidity in the immediate post‐accident period.
Familial Transmission of Alcohol Use Norms and Expectancies and Reported Alcohol Use
Authors: Johnson Ronald C. , Nagoshi Craig T. , Danko George P. , Honbo Kelly Ann M. , Chau Lai Ling
Published: April 2006

Members of 183 families (biological parents and one adult offspring) completed questionnaires on their quantity and frequency of alcohol use, what they would consider a “normal'’quantity‐frequency of alcohol use, “problem” quantity‐frequency of use, flushing after alcohol use, and other expected physiological and subjective responses to alcohol. Within individuals, own quantity‐frequency of alcohol use was moderately negatively correlated with flushing after one drink or less (“fast flushing”), but more highly positively correlated with judged normal alcohol use and with expected subjective effects. Spouse resemblances were low for quantity‐frequency of alcohol use and flushing, but high for alcohol use norms and expected physiological and subjective responses. Parent‐offspring resemblances were low to moderate for own alcohol use and flushing, but moderate to high for expected physiological and subjective effects. These results were discussed in terms of the effects of genetically transmitted flushing after alcohol use and culturally transmitted alcohol norms and expectations on alcohol use.
Alterations in Interleukin‐2 Utilization by T‐Cells from Rats Treated with an Ethanol‐Containing Diet
Authors: Jerrells Thomas R. , Perritt David , Eckardt Michael J. , Marietta Cheryl
Published: April 2006

Administration of ethanol to Sprague‐Dawley rats has been shown to produce a defect in lymphocyte proliferation in response to concanavalin A. Because a critical element in T‐cell proliferation is the production of interleukin‐2, experiments were designed to evaluate the influence of ethanol on the production and utilization of interleukin‐2 by spleen cells from ethanol‐treated animals. To ensure that changes in spleen cell responses to mitogenic stimulation were not simply caused by a loss of responding T cells, we tested nylon wool‐nonadherent cells. The response to concanavalin A of isolated T cells from ethanol‐treated rats was consistently less than that of equivalent numbers of cells from control animals. The addition of recombinant interleukin‐2 to cultures of T cells did not correct the defect in proliferation to concanavalin A noted in cells from ethanol‐treated rats. Further study results demonstrated that interleukin‐2 production by T cells from ethanol‐treated animals was equal to or greater than that by cells from animals given control diet. Blast cells recovered from 48‐hr concanavalin A‐stimulated spleen cell cultures from ethanol‐treated animals, however, showed a decreased ability to proliferate in response to exogenous interleukin‐2. Binding of 125I‐interleukin‐2 to blast cells resulting from concanavalin A stimulation, under conditions that detected high‐affinity binding, was similar in cells from treated and control animals. These data indicate that the deficiency in proliferation of lymphocytes from ethanol‐treated animals is not caused by a lack of interleukin‐2 production by the T cells. It is also apparent that T cells from ethanol‐treated rats are not deficient in high‐affinity interleukin‐2 receptors.
Diagnostic Value of Serum γ‐Glutamyl‐Transferase Activity and Mean Corpuscular Volume in Alcoholic Patients with or without Cirrhosis
Authors: Pol Stanislas , Poynard Thierry , Bedossa Pierre , Naveau Sylvie , Aubert Alain , Chaput Jean‐Claude
Published: April 2006

In an attempt to assess the diagnostic values of serum γ‐glutamyl‐transferase (GGT) and mean corpuscular volume (MCV) variations as markers of liver disease and of abstinence in alcoholic patients, we compared 174 patients with alcoholic cirrhosis, 175 with noncirrhotic alcoholic liver disease and 67 patients with nonalcoholic cirrhosis. GGT and MCV values were checked three times, the day of admission, 7 days later, and on the last sample available during follow‐up (1 to 12 months), and were compared according to the liver disease and abstinence.

A decrease of GGT activity during the 1st week of hospitalization was noted in alcoholics with (‐9 IU/liter) or without (‐13 IU/liter) cirrhosis and not in nonalcoholic cirrhosis (+8 IU/liter), without MCV variations. During follow‐up, median GGT activity was strikingly different in abstinent patients with (27 IU/liter) or without (21 IU/liter) cirrhosis and in nonabstinent patients (99 IU/liter and 123 IU/liter, respectively) (p < 0.001). MCV decrease was noted in alcoholics whatever their abstinence or not, contrasting with the absence of decrease in nonalcoholic patients. For the diagnosis of alcoholism in cirrhotic patients, the positive predictive value (PPV) of a GGT or a MCV decrease during the 1st week of hospitalization was 0.82 and 0.78, respectively, and the negative predictive value (NPV) was 0.33 and 0.70, respectively. For abstinence during follow‐up, the PPV of a GGT activity < 50 IU/liter was 0.92 and the NPV was 0.65. In multidimensional stepwise regression analysis, the GGT decrease appeared independently associated with initial GGT activity (p < 0.001) and with alcohol withdrawal (p < 0.001) while MCV decrease was only associated with the initial MCV value.

GGT and MCV do appear per se as weak indicators of alcoholism during liver diseases. Inversely, the early decrease of serum GGT activity, which is independent of the type of the liver disease, and a frank decrease of MCV during follow‐up of out‐patients are markers of alcoholism. A persistent decrease of GGT activity to normal or under 2.5‐fold normal values is a marker of abstinence in alcoholics with or without cirrhosis.
Plasma Tumor Necrosis Factor α Predicts Decreased Long‐Term Survival in Severe Alcoholic Hepatitis
Authors: Felver Michael E. , Mezey Esteban , McGuire Marielena , Mitchell Mack C. , Herlong H. Frank , Veech George A. , Veech Richard L.
Published: April 2006

Plasma tumor necrosis factor α (TNF α), interleukin 1 α (IL‐1α), and interleukin 1 β (IL‐1β) were measured in plasma samples obtained from 23 patients with severe alcoholic hepatitis on admission and after 30 days of hospitalization. Over a 2‐year follow‐up period, 14 patients died at a mean time of 8 months following discharge. The presence of elevated plasma TNF α either at admission or discharge from the hospital was associated with death in 82% (14/17) of patients. By contrast absence of elevated plasma TNF α was associated with survival in 100% (6/6). The difference in survival with and without detectable plasma TNF α was significant at p= 0.0022. Plasma TNF α was not elevated in alcoholic patients without clinically apparent liver disease, with alcoholic cirrhosis, or in nonalcoholic healthy controls. Plasma IL‐1a was also significantly increased in alcoholic hepatitis whereas IL‐1β was not. Neither IL‐1α nor β was correlated with outcome in the alcoholic hepatitis group. It is concluded that the presence of elevated plasma TNF α is a significant predictor of decreased long‐term survival in patients with severe alcoholic hepatitis.
Effects of Prenatal Ethanol and Long‐Chain n‐3 Fatty Acid Supplementation on Development in Mice. 1. Body and Brain Growth, Sensorimotor Development, and Water T‐Maze Reversal Learning
Authors: Wainwright P. E. , Ward G. R. , Winfield D. , Huang Y‐S. , Mills D. E. , Ward R. P. , McCutcheon D.
Published: April 2006

Pregnant mice were fed equivalent daily amounts of a liquid diet containing 25% (kcal) ethanol, or with maltose dextrin substituted isocalorically for ethanol. In addition, the diet contained 20% oil; this was either of two mixtures, one comprised of predominantly n‐6 (18:2n‐6) fatty acids, and the other containing an equivalent amount of n‐6, but supplemented with a source of long chain n‐3 (20:5n‐3, 22:6n‐3) fatty acids. An additional control group was fed lab chow ad libitum. The treatment was implemented from day 7 to 17 of gestation, whereafter all groups were fed lab chow. Ethanol decreased maternal weight gain and pup body and brain weight; it also retarded both sensory and motor development in the pups and impeded reversal learning in a water maze. The n‐3 supplementation lowered maternal blood alcohol concentration, but counteracted only some of the effects of ethanol, by increasing maternal weight gain and pup body weight, and also by enhancing sensory development in the pups. Such effects were additive, in that they were also present in the maltose‐dextrin control group. These findings suggest that n‐3 supplementation may ameliorate some of the effects of ethanol on neurobehavioral development, but the magnitude of the effect appears to be small.
Gestational Ethanol Consumption on Tissue Amino Acid Levels: Decreased Free Histidine and Tryptophan in Fetal Tissues with Concomitant Increase in Urinary Histamine Excretion
Authors: Lin Grace W.‐J. , Lin Tsau‐Yen , Jin Liying
Published: April 2006

The effects of ethanol consumption during pregnancy on maternal, placental, and fetal tissue amino acid levels and metabolism were investigated. Pregnant Sprague‐Dawley rats were given 35% ethanol‐calorie liquid diet, ad libitum, from gestation day 7 to 21. Control rats were pair‐fed with isocaloric sucrose substituted for ethanol. Ethanol consumption decreased fetal body weight and increased placental weight. Twenty‐four amino acids were determined in six tissues (maternal plasma and liver, placenta, fetal plasma, liver, and brain) by HPLC with orthophthalaldehyde derivatization. The effects of ethanol on free amino acid levels differed from tissue to tissue. In general, ethanol affected more amino acids in maternal plasma, fetal plasma, and liver. Maternal liver, placenta, and fetal brain amino acids were more resistant to ethanol effect. Two essential amino acids, histidine and tryptophan, were consistently decreased in fetal tissues by maternal ethanol consumption. The values (ethanol vs. control, nmole/ml or g, mean ± SEM,N= 20) of fetal Plasma, liver, and brain for histidine were 51.8 ± 6.0 vs. 85.3 ± 4.5 (p= 0.001), 269.0 ± 26.4 vs. 503.7 ± 47.3 (p= 0.0004), and 117.9 ± 7.7 vs. 154.6 ± 8.7 (p= 0.0055), respectively; and for tryptophan were 105.7 ± 3.1 vs. 132.2 ± 4.1 (p= 0.0001), 128.8 ± 3.7 vs. 144.3 ± 6.0 (p= 0.0407), and 83.4 ± 7.2 vs. 103.6 ± 3.2 (p= 0.0198), respectively. Histidine was also decreased in placenta by ethanol (138.1 ± 6.6 vs. 189.1 ± 11.8 nmole/g,p= 0.0014). By contrast, the concentrations of histidine and tryptophan in maternal plasma and liver were either unaffected or increased by ethanol. Histidine and tryptophan are the precursors of neurotransmitters, histamine and serotonin, respectively, and since FAS has a high incidence of CNS dysfunction, it is suggested that reduced levels of histidine and tryptophan in fetal brain from ethanol group may have significant implication. Placenta transport study with14C‐histidine observed no inhibitory effect of ethanol. Histamine excretion was increased in the urine from the ethanol‐treated rats as compared with the controls. On gestation day 20, the increase was 173% (mean ± SEM, 674 ± 52 vs. 247 ± 32μg/24 hr urine,N= 20,p< 0.0001). Significant, negative correlations between urinary histamine and fetal and placental histidine were observed. Thus, the decreased histidine contents observed in fetal and placenta tissues from the ethanol‐treated group could be the result of enhanced production of histamine depleting the histidine pool.