bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain and Liver Dolichol in Chronic Alcoholism: A Necropsy Study
Authors: Kril Jillian J. , Pullarkat Raju K. , Pullarkat Premila S. , Harper Clive G.
Published: April 2006

Cerebral gray and white matter and liver dolichol levels were measured in postmortem samples from chronic alcoholics and nonalcoholic controls following recent suggestions that dolichol levels may be used as a marker for alcoholism. No significant differences in brain dolichol were found between the control and alcoholic groups. A significant reduction in the liver dolichol was observed in the alcoholic group. This was most marked in those alcoholics with liver disease.
Maternal Genetic Effects on Ethanol Teratogenesis and Dominance of Relative Embryonic Resistance to Malformations
Authors: Gilliam David M. , Irtenkauf Keith T.
Published: April 2006

Maternal genetic factors and/or fetal genetic factors contribute to variations in response to prenatal alcohol exposure. To assess the contribution of maternal genotype to ethanol teratogenesis, a reciprocal cross study was conducted in an animal model using C57BL/6J (B6) and long‐sleep (LS) mice. B6 mice are more susceptible than LS mice to prenatal ethanol‐induced malformations but both mouse stocks are susceptible to fetal weight deficits following in utero alcohol exposure. B6 and LS dams were reciprocally mated to B6 or LS males producing four embryonic genotype groups: the true‐bred B6B6 and LSLS genotypes, and the genetically similar B6LS and LSB6 genotypes (the F1 genotype). Dams were intubated with either 5.8 g/kg ethanol (E) or an isocaloric amount of sucrose (S) on day 9 of pregnancy. Fetuses were removed on gestation day 18, weighed, and assessed for soft tissue or skeletal malformations. Results showed a greater litter weight deficit and increased total malformation rate in ethanol‐exposed F1 litters carried by B6 mothers compared to ethanol‐exposed F1 litters carried by LS mothers. This result would be expected only if maternal genetic factors contribute significantly towards susceptibility to ethanol teratogenesis. The influence of the LS mother was to decrease susceptibility to ethanol teratogenesis compared to the B6 mother while the influence of the B6 mother was to increase susceptibility to ethanol teratogenesis compared to the LS mother.

The average malformation rate for F1 litters was significantly less than the predicted midparental value. This shows that the F1 genotype exhibited dominance towards resistance to prenatal alcohol effects. There was no differential effect of prenatal treatment on male and female fetuses for any embryonic genotype, indicating that the differential teratogenic response between F1 litters was not due to sex‐linked traits. Likewise, weight gain due to pregnancy and maternal blood ethanol levels did not differ among genotypes.

It was concluded that genetic factors differentially influence maternal physiological response to ethanol, which in turn affects teratogenic responses in F1 litters. Separation of maternal physiological mechanisms from fetal mechanisms responsible for ethanol teratogenic susceptibility is needed for targeting women and infants at risk. Such knowledge will help in formulating effective therapeutic intervention strategies.
Murine Model of Ethanol‐Induced Immunosuppression
Authors: Jerrells Thomas R. , Smith Wiley , Eckardt Michael J.
Published: April 2006

Alcohol abuse has been associated with an increased susceptibility to infectious diseases and certain tumors. On the basis of these obsevations, an effect of ethanol on the immune system has been suggested. We have used a mouse model system in which male C57B1/6 mice were fed either Lieber‐DeCarli liquid diet containing ethanol sufficient to supply 37% of the total calories or isocaloric control diet in a pair‐feeding design to examine the effect of ethanol on the immune system. The group consuming the ethanol‐containing diet maintained relatively stable levels of blood ethanol for the 8 days of feeding. Consumption of ethanol for 8 days resulted in a profound loss of thymus and spleen cells, and the recovery of thymus cellularity was delayed relative to the recovery of spleen cell numbers after ethanol feeding was discontinued. Proliferation of spleen lymphocytes to T‐cell stimuli (concanavalin A and alloantigens) was diminished; however, B‐cell proliferation to lipopolysaccharide was relatively unchanged in mice fed ethanol‐containing diet. Also in ethanol‐fed mice a significant decrease in the primary antibody response to sheep red blood cells but not to the T‐independent antigen trinitrophenol‐ficoll occurred. These data establish the murine model system as a means to define further the effect of ethanol on the immune system and host defense mechanisms.
Deranged Vitamin D Metabolism but Normal Bone Mineral Density in Finnish Noncirrhotic Male Alcoholics
Authors: Laitinen Kalevi , Välimäki Matti , Lamberg‐Allardt Christel , Kivisaari Leena , Lalla Martti , Kärkkäinen Merja , Ylikahri Reino
Published: April 2006

To study the effect of prolonged ethanol consumption on calcium metabolism and on the prevalence of osteoporosis we examined 38 Finnish noncirrhotic male alcoholics (30–55 years of age) with dietary interviews and biochemical measurements and by measuring the bone mineral content of the forearm using single photon absorptiometry (SPA) and the bone mineral density of the spine, humerus and proximal femur using nonquantified computer tomography (CT) and dual‐energy x‐ray absorptiometry (DEXA). In comparison two groups of healthy controls were studied. The mean daily dietary intake of calcium was 1.3 g in the patients and 1.2 g in the controls. The dietary intake of vitamin D was equal in the study groups, too. The serum levels of calcium, phosphate and parathyroid hormone did not show any difference between the patients and controls but in the alcoholics the urinary excretion of calcium was reduced by 42% (p < 0.0001) as compared to the controls. The serum levels of 25‐hydroxyvitamin D3, 1,25‐dihydroxyvitamin D3, and 24,25‐dihydroxyvitamin D3 were reduced in the alcoholics by 40% (p < 0.0001), 23% (p < 0.01), and 48% (p < 0.0001), respectively, as compared to the controls. The alcoholic men had normal levels of serum testosterone and they did not have hypercortisolism. The bone mineral content of the dominant forearm measured by SPA was similar in the study groups as were the bone mineral densities (BMD) of the lumbar and humeral areas measured by CT. The BMD at the lumbar, femoral neck, Ward's triangle and trochanter sites measured by DEXA did not differ, either. We conclude that bone mass is not reduced in noncirrhotic male alcoholics who have a high calcium intake and who are not hypogonadal. However, the metabolism of vitamin D is deranged by chronic ethanol consumption.
The Detection of Alcoholism in Hospitalized Schizophrenics: A Comparison of the MAST and the MAC
Authors: Searles John S. , Alterman Arthur I. , Purtill James J.
Published: April 2006

The Michigan Alcoholism Screening Test (MAST) and the MacAndrew Alcoholism Scale (MAC) were administered to forty‐one schizophrenic inpatients also meeting DSM‐III criteria for either alcohol abuse or alcohol dependence and 29 schizophrenic inpatients who did not qualify for an additional substance abuse diagnosis other than marijuana abuse/dependence. The MAC failed to differentiate between the alcoholic and nonalcoholic groups and both groups scored above the recommended cutting score. The MAST significantly differentiated the alcoholic and nonalcoholic schizophrenic patients and was as sensitive to a history of alcohol abuse as to alcohol dependence. Neither the MAST nor MAC was sensitive to recent versus more remote drinking. The overall classificatory accuracy of the MAST was found to be 80% and that of the MAC was 56%. A logistic regression analysis revealed that the use of just four MAST items can yield a group classificatory rate of 83%. It was concluded that the MAST exhibited sufficient sensitivity and specificity to be used as an initial screening instrument for alcoholism in schizophrenic patients.
Alcohol Protects the Diaphragm during Dietary Restriction
Authors: Reid Michael B. , Shannon Kathy , Feldman Henry A. , Miller Michael J.
Published: April 2006

We recently reported that alcoholic rat diaphragm develops greater contractile force than diaphragm of pair‐fed control animals. The present experiment examines whether alcohol or dietary restriction is the more likely cause of this surprising finding. We conditioned 10 rats using a liquid diet containing ethanol as 36% of calories. Ten pair‐fed control animals received an equal amount of isocaloric, ethanol‐free liquid diet. Ten ad libitum control animals had unrestricted access to lab chow and water. Rats were killed after 30 weeks. Left costal diaphragm strips were studied in vitro at optimal length using direct stimulation at supramaximal voltage. Isometric force was measured and divided by muscle cross‐section to compute stress. Maximal tetanic stresses developed by muscle from pair‐fed controls were systematically less than alcoholic and ad libitum control values (p < 0.0001); this did not depend on temperature (25° vs. 37°p > 0.50). Pair‐feeding increased twitch half‐relaxation times (p < 0.03) and shifted the tetanic stress‐stimulation frequency relationship leftward by 10 Hz (p < 0.01). Diaphragm of pair‐fed rats continued to generate lower stresses during the fatigue caused by repeated contractions (p < 0.01). We conclude that dietary restriction associated with pair‐feeding compromises diaphragm performance in rats. Chronic alcohol consumption prevents or reverses these changes, since diaphragm function of alcoholic and ad libitum control animals was not different.
Participation of Phosphoinositides in Gastric Mucosal Protection by Colloidal Bismuth Subcitrate against Ethanol‐Induced Injury
Authors: Slomiany Bronislaw L. , Wang Xiaoying , Palecz Danuta , Okazaki Kazuichi , Slomiany Amalia
Published: April 2006

The mechanism of gastric mucosal protection by an antiulcer agent, colloidal bismuth subcitrate (CBS), against ethanol‐induced injury was investigated using in vivo and in vitro systems. The experiments in vivo were conducted with groups of rats with and without indomethacin pretreatment, and the animals received either a dose of CBS (100 mg/kg) or a vehicle (saline), followed 30 min later by ethanol. In the in vitro studies, gastric mucosa segments were cultured in the presence of CBS, ethanol, or both. The results of in vivo experiments revealed that in the absence of CBS, ethanol caused extensive gastric hemorrhagic lesions which were significantly reduced following CBS pretreatment and this effect of CBS was not prevented by indomethacin. The data obtained with gastric mucosal culture established that in comparison to the controls, ethanol caused a 27% decrease in mucin synthesis, while mucin synthesis in the presence of CBS increased by 48%. The increase in mucin synthesis evoked by CBS was accompanied by the enhanced metabolism of mucosal phosphoinositides, as reflected by a decrease in PI (15%) and PIP2 (30%), and an increase in IP1 (26%) and IP3 (67%). In contrast, ethanol, which exhibited detrimental effect on mucin synthesis, caused a decrease in PIP (35%), IP2 (47%) and IP3 (38%), and an increase in PIP2 (80%), and IP1 (51%). However, when the mucosal culture was carried out in the presence of both CBS and ethanol, the detrimental changes evoked by ethanol on mucin synthesis were prevented, and the phosphoinositide and inositide phosphate distribution patterns were quite similar to those in the mucosa cultured in the presence of CBS only. The results indicate that CBS is capable of overcoming the untoward effect of ethanol on phosphoinositide‐specific phospholipase C, thus restoring phosphoinositide‐derived messenger molecule metabolism essential for cellular proliferation and mucus synthesis, the key factors in gastric mucosal defense.
Ethanol‐Inducible Cytochrome P‐450: Assessment of Substrates' Specific Chemical Probes in Rat Liver Microsomes
Authors: Lucas D. , Berthou F. , Dreano Y. , Floch H. H. , Menez J. F.
Published: April 2006

The capacity of liver microsomes to oxidize various substrates known to be specific of alcohol‐inducible cytochrome P‐450 was studied in rats treated with different xenobiotics such as 3‐methyl‐cholanthrene, phenobarbital, acetone, and ethanol. Analysis of results showed a significantly marked increase following ethanol and acetone treatments of the p‐nitrophenol hydroxylation (283 ± 19% and 304 ± 21%), N‐nitrosodimethylamine (NDMA) demethylation (280 ± 105% and 228 ± 95%), benzene hydroxylation (258 ± 60% and 236 ± 61%), butanol oxidation (173 ± 34% and 154 ± 32%), aniline hydroxylation (147 ± 22% and 95 ± 8%), and ether de‐ethylation (95 ± 17% and 83 ± 17%) and a not significant increase of N‐nitrosodiethylamine (NDEA) de‐ethylation (34 ± 11% and 9 ± 8%) in rat microsomes, respectively, versus control animals (mean ± SD, values expressed as nmol/min/nmole P‐450). All of these activities significantly decreased after 3‐MC treatment, except for the p‐nitrophenol hydroxylation. PB treatment markedly enhanced NDEA de‐ethylation, p‐nitrophenol, and benzene hydroxylations (106 ± 38%, 109 ± 14%, and 153 ± 62%, respectively) versus controls. These results suggest that NDMA and especially 1‐butanol are the most specific and useful probes of alcohol‐inducible cytochrome P‐450 in crude liver microsomes.
Effects of Alcohol on the Import of Aldehyde Dehydrogenase Precursor into Rat Liver Mitochondria
Authors: Wang Thomas T. Y. , Pak Youngmi K. , Weiner Henry
Published: April 2006

We previously showed that incubation of rat liver motochondria with alcohols resulted in the inhibition of the import of aldehyde dehydrogenase precursor but not that of ormithine transcarbamylase precursor (Wang TTY, Farrés J, and Weiner H: Arch Biochem Biophys 272:440–449, 1989). The time required for inhibition of import to occur was now measured with ethanol (200 mM) and butanol (100 mM) at 0° and 30°C. It required approximately 30 min to achieve 50% inhibition with butanol and 50 min with ethanol. To further substantiate the membrane perturbing effects of alcohols, we also examined the effect of oleic acid on import. We found that incubation of mitochondria with oleic acid (0–100 μM) resulted in inhibition of aldehyde dehydrogenase precursor import in a dose response fashion. In addition to in vitro effects of alcohols on import, we conducted a preliminary study on import of protein into liver mitochondria isolated from rats fed ethanol. We found that the rate of aldehyde dehydrogenase precursor import into liver mitochondria isolated from ethanol fed rats was identical to that from control. The results are consistent with finding that the activity and amount of aldehyde dehydrogenase was the same in mitochondria isolated from the alcohol‐fed or control animals.
Examination of Cloninger's Type I and Type II Alcoholism with a Sample of Men Alcoholics in Treatment
Authors: Penick Elizabeth C. , Powell Barbara J. , Nickel Elizabeth J. , Read Marsha R. , Gabrielli William F. , Liskow Barry I.
Published: April 2006

Cloninger's clinical method of classifying alcoholics into two groups (Types I and II) was examined with data obtained from 360 VA hospitalized male alcoholic patients. For operational criteria, the Cloninger clinical method of subtyping alcoholics employs age‐of‐onset of problem drinking and symptom‐clusters supposedly associated with each subtype. Marked overlap was found between the symptom‐clusters used to define the two subtypes. Ninety‐one percent of the entire sample satisfied criteria for both symptom‐clusters. Dividing the sample by early‐onset (Type II, ≤25 years) and lateonset (Type I, >26 years) alcoholism did not substantially reduce the overlap between symptom‐clusters; i.e., 96% of the early‐onset and 83% of the late‐onset subgroups were positive for both symptomclusters. Only 21 men (6%) could be classified when both age‐of‐onset and the type‐appropriate symptom‐cluster were used to separate patients. In hospital settings, at least, these findings suggest that the two‐group clinical alcoholism typology proposed by Cloninger basically reflects the age‐of‐onset of problem drinking.
Attention Deficits in Children Exposed to Alcohol Prenatally
Authors: Nanson J. L. , Hiscock M.
Published: April 2006

Twenty children with fetal alcohol syndrome or fetal alcohol effect (FAS/FAE) were compared with 20 attention deficit disorder (ADD) children and 20 normal controls on three experimental tasks designed to isolate four different components of attention. Parents completed three questionnaires regarding their child's activity level and overall functioning, and the children completed a short form of an IQ test. The children in each group ranged from 5 to 12 years. Results indicate that although the children with FAS/FAE are significantly more impaired intellectually, their attentional deficits and behavioral problems are similar to those of children with ADD. These findings imply that the treatments known to facilitate learning in children with ADD may also benefit children with FAS/FAE.
Utility of the Self‐Administered Alcoholism Screening Test (SAAST) in Schizophrenic Patients
Authors: Smith Cedric M. , Pristach Cynthia A.
Published: April 2006

The utility of the Self‐Administered Alcoholism Screening Test (SAAST) in determining alcohol abuse and alcoholism was assessed in a preliminary study of 21 schizophrenic patients during their hospitalization in an acute care psychiatric unit; on admission all met DSM‐III‐R criteria for schizophrenia and none were detected to have any alcohol‐related diagnosis. SAAST scores ranged from 2 to 26 with a mean score of 10.8. Forty‐eight percent (10/21) had SAAST scores greater than or equal to 10, indicating “probable alcoholism”; 62% (13/21) scored 8 or higher. Every patient with a SAAST score of 8 or higher also met DSM‐III‐R criteria for alcohol abuse or dependence on the basis of patient interview, independent chart reviews, and interviews of significant others. In contrast, only half (5/10) of the high SAAST scorers would actually admit to a problem with drinking during the extensive study interviews. Six SAAST items were found to be highly predictive of abuse or alcoholism; the SAAST had greater sensitivity than the interviews. Sixty‐two percent (8 of 13) of the schizophrenic patients who met the DSM‐III‐R criteria for alcohol abuse reported a first degree relative with an alcohol‐related problem, in contrast to only 25% of the “nonalcoholic” patients. The patterns of the alcoholic schizophrenic patients' responses on the different SAAST items revealed even greater denial and lack of insight than those of nonschizophrenic alcoholic subjects.
A Comparative Blinded Study in Miniature Swine of Whole Blood‐, Hemoglobin‐, Platelet‐, Plasma‐, and Lymphocyte‐Associated Acetaldehyde as Markers for Ethanol Intake
Authors: Peterson C. M. , Scott B. K. , Sun Grace Y. , Sun Albert Y.
Published: April 2006

Blood samples were obtained from miniature swine maintained on 0, 2, or 6 g/kg/24 hr ethanol for 8 months (N= 6 in each group). Samples from drinking pigs were taken after 8 hr of ethanol abstinence and all were coded and sent for “blinded” analysis. A fluorigenic high performance liquid chromatographic assay was used to quantify whole blood‐associated acetaldehyde, hemoglobin‐associated acetaldehyde, plasma‐associated acetaldehyde, platelet‐associated acetaldehyde, and lymphocyte‐associated acetaldehyde. Detectable levels of acetaldehyde were found in each sample in both drinking and nondrinking pigs. Analysis of whole blood‐associated acetaldehyde was most discriminatory in distinguishing nondrinking from drinking pigs (mean 21.4 ± 1.0 μM for nondrinkers vs. 24.6 ± 1.5 so for the group consuming 2 g/kg ethanol, p= 0.001). Measurements of hemoglobin‐associated acetaldehyde normalized to protein concentration (250 ± 47 nmoles/g vs. 203 ± 33 SD, p < 0.05 drinking vs. nondrinking pigs) and platelet‐associated acetaldehyde (0.46 0.34 vs. 0.15 ± 0.16 nmoles/3 × 10° platelets, p= 0.05 drinking vs. nondrinking pigs) were also useful in discriminating drinking from nondrinking animals. Analysis of plasma‐associated acetaldehyde and lymphocyte‐associated acetaldehyde were not useful as markers of ethanol consumption. The miniature swine proved to be a useful model for the evaluation of these potential markers of ethanol intake. In this model, increased amounts of acetaldehyde can be found in several blood compartments eight hr after cessation of ethanol. Further work is warranted to define the relative kinetics of each measurement and the potential utility of each as a marker for ethanol consumption in man.
Electrophysiological Effects of Ethanol on Monoaminergic Neurons: An in Vivo and in Vitro Study
Authors: Verbanck P. , Seutin V. , Dresse A. , Scuvée J. , Massotte L. , Giesbers I. , Kornreich C.
Published: April 2006

Monoaminergic neurons have been shown to play a role in both the intoxicating and chronic effects of ethanol. We present here the results of a study about the acute effects of ethanol on serotonergic raphe nucleus, noradrenergic locus coeruleus, and dopaminergic ventral tegmental area. These nuclei were investigated electrophysiologically by recording the spontaneous firing rate of single neurons using glass microelectrodes, both in vivo in chloral hydrate anesthetized rats and in vitro in brain slices. Ethanol was perfused intravenously at a rate ranging from 0.2 mg/kg/min to 0.2 g/kg/min in vivo, and at concentrations between 10‐8 M and 1 M in vitro. We observed that each monoaminergic nucleus had its own pattern of responses to acute ethanol perfusion, and that high and low concentrations have different actions, suggesting a biphasic effect. For example, in slices, ethanol concentrations higher than 10 mM induce an excitation in most raphe and ventral tegmental area neurons, and an inhibition of firing in locus coeruleus neurons. The results were comparable in the in vivo model, but much more heterogenous. We conclude that the effect of ethanol on the monoaminergic neurons is specific of the type of neuron, and that a biphasic effect is commonly found.
Effects of Acute Alcohol Intake on Tolerance to Hypotension
Authors: Bottoms G. D. , Fessler J. F. , Johnson M. , Coatney R. W. , Voorhees W.
Published: April 2006

The specific aim of this research was to test the hypothesis that intoxication with alcohol results in poor tolerance to hemorrhage. This was evaluated on the basis of blood pressure, cardiac output respiratory rate, blood flow to organs, and survival for 4 hr after hemorrhage. Four groups of six swine per group were used (control, intoxicated, hemorrhage, and intoxicated‐hemorrhage). The results revealed that blood alcohol concentrations near 0.1% greatly reduced tolerance to hemorrhage. intoxicated animals subjected to hemorrhage were unable to maintain an adequate cardiac output, blood pressure, or respiratory rate to sustain life. Pigs tolerated higher blood alcohol concentrations, up to 0.35%, when not exposed to hemorrhage. Also, unintoxicated pigs were able to compensate for severe hemorrhage. Only one of the six pigs in the intoxicated‐hemorrhage group survived for 4 hr after hemorrhage. In conclusion the body's ability to compensate and recover from hemorrhage was greatly reduced during intoxication. It is logical to assume that the ability to overcome numerous other stressors may also be reduced during intoxication.
Cell Population Depletion Associated with Fetal Alcohol Brain Damage: Mechanisms of BAC‐Dependent Cell Loss
Authors: West James R. , Goodlett Charles R. , Bonthius Daniel J. , Hamre Kristin M. , Marcussen Britt L.
Published: April 2006

Neuronal death is one of the most serious consequences of alcohol exposure during development. Studies described in this paper used a neonatal rat model to address factors affecting neuronal death following alcohol exposure during the period of rapid brain growth, and relate them to possible mechanisms of damage. The profile of blood alcohol concentrations (BACs) is an important variable influencing both brain growth deficits and neuronal death—a smaller daily dose of alcohol can be more damaging than a larger daily dose, if it is consumed in a binge‐like pattern that produces relatively higher BACs. Alcohol exposure for a single day also can be damaging, producing both brain growth deficits and neuron loss, if high BACs are obtained. Various brain regions and different neuronal populations within a given brain area exhibit different degrees of vulnerability. Some neuronal loss clearly is a function of cell death due to direct effects of alcohol, while other deficits may be due to either primary or secondary effects of the alcohol insult. In the cerebellum, a maturational or metabolic factor also appears to be involved with alcohol‐induced neuronal death. Immunocytochemical studies using a monoclonal antibody against microtubule‐associated protein 2 (MAP2) indicated that cerebellar lobules containing Purkinje cells that are in the process of extending dendrites are ones that are more vulnerable to alcohol than lobules containing Purkinje cells that mature later. Alcohol exposure during brain development may be producing neuron attrition in multiple ways, including disruption of membrane integrity, inhibition of protein synthesis or other alterations such as lipid solubility, or by disruption of cytoskeletal elements.
Hemoglobin‐Acetaldehyde Adducts in Human Volunteers Following Acute Ethanol Ingestion
Authors: Niemelä Onni , Israel Yedy , Mizoi Yasuhiko , Fukunaga Tatsushige , Eriksson C. J. Peter
Published: April 2006

Rabbit antibodies against albumin‐acetaldehyde adduct were used in an enzyme‐linked immunosorbent assay to detect acetaldehyde‐hemoglobin condensates from the blood of 12 volunteers following ingestion of 1.3 to 2.9 g of ethanol per kg body weight during 8 hr. Blood samples were drawn before drinking and between 2 to 46 hr after starting the drinking session. While there were no significant increases in blood acetaldehyde levels in these samples, acetaldehyde‐hemoglobin adducts were significantly increased in the samples drawn after ethanol had been eliminated from the body. Administration of ethanol (0.1 g/kg) to an Oriental flusher resulted in an increase both in blood acetaldehyde and the hemoglobin‐acetaldehyde adduct levels. These results suggest that acetaldehyde‐hemoglobin condensates are formed in vivo following acute ethanol ingestion. Such condensates may be of value to mark alcohol consumption.
Detection of a New Acetaldehyde‐Induced Hemoglobin Fraction HbA1ach by Cation Exchange Liquid Chromatography
Authors: Sillanaukee Pekka , Koivula Timo
Published: April 2006

We developed a sensitive cation exchange liquid chromatographic method for analysis of acetaldehyde binding with hemoglobin. When human hemolysates were incubated in vitro with micromolar concentrations of acetaldehyde without reducing agents, HbAo was found to form two new fractions. One of them was eluated with HbA1c, whereas a novel, previously undescribed fraction was detected between HbF and HbA1c. This new fraction was termed HbA1sch. The mean within‐assay variation for the different hemoglobin fractions varied from 0.45 (HbA0) to 8.2% (HbA1ach) and the between‐assay variation from 0.6 to 19.3%, respectively. After incubation with [1,214C]acetaldehyde the specific radioactivity of HbA1ach was about 10 times higher than that of HbA0 and twice as high as the activity of the HbA1c fraction.

The reaction kinetics of the formation of hemoglobin adducts were studied in vitro by incubation of hemolysates with various acetaldehyde concentrations. Acetaldehyde caused both short‐term and permanent changes in hemoglobin. Even low acetaldehyde concentrations from 10 to 100 μmol/liter caused detectable changes in hemoglobin. During incubation the amount of HbA1ach and HbA1c fractions increased rapidly within the first 10 min and decreased slowly during the next hr but did not return to the initial levels. This suggests that only the part of binding of acetaldehyde with hemoglobin is irreversible and the changes can be already detected after incubation with physiological acetaldehyde concentrations.
The Michigan Alcoholism Screening Test: False Positives in a College Student Sample
Authors: Martin Christopher S. , Liepman Michael R. , Young Christopher M.
Published: April 2006

The Michigan Alcoholism Screening Test (MAST), designed and validated by Selzer (1971), is widely used to screen for persons with alcohol problems. The most recent version of the MAST includes the question “Have you ever attended a meeting of Alcoholics Anonymous (AA)?”. This question may contribute to false positive identifications, as it does not specify whether attendance is for the subject's own problem drinking. In the current research, 114 college students completed the MAST along with an additional question: “Have you ever attended a meeting of Alcoholics Anonymous because of your own problem drinking?”. The results indicated that seven of 114 subjects (6.1%) attained inflated MAST scores because they had attended an Alcoholics Anonymous meeting, but not for their own problem drinking. It is suggested that the wording to the Alcoholics Anonymous question on the MAST be changed to reduce the number of false positive identifications produced by this instrument.
Dendritic Hypertrophy in Purkinje Neurons of Old Fischer 344 Rats after Long‐Term Ethanol Treatment
Authors: Pentney Roberta J. , Quackenbush Laurie J.
Published: April 2006

Metric parameters of Purkinje cell dendritic networks in 24‐ to 26‐ month‐old Fischer 344 rats were determined after 48 weeks of chronic ethanol intake. Measurements included the total number and length of all segments/network, the total number and length of segments within topologically defined segment categories, and the mean length of segments in each category. A main effect of ethanol was expressed as a significant increase in cumulative length within one category of terminal segments. This increase was the result of a significant increase in mean length/segment in that category. Metric changes in other segment categories were not significant, showing that changes in the networks during ethanol treatment were not distributed randomly. Recovery after ethanol treatment was associated with further nonrandom remodeling of these networks. Significant differences in lengths of terminal segments were no longer present, but internal segments in networks of both pair‐fed and ethanol‐fed rats were significantly longer. Only one category of internal segments showed this change during recovery. The data showed that long term ethanol treatment in old rats, at a time when effects of aging processes were prominent in Purkinje cell networks, was associated with remodeling of those networks through dendritic extension. This effect was interpreted as compensatory growth in surviving networks following ethanol‐related neuronal loss and/or damage to the surrounding neuropil. Recovery from dietary treatment produced further internal remodeling of those networks that was not related specifically to ethanol. It could be shown, however, that the restructuring processes that resulted in longer internal segments after dietary recovery were different in the pair‐fed and the ethanolfed rats.
The Bidirectional Effects of Shock on Alcohol Preference in Rats
Authors: Volpicelli Joseph R. , Ulm Ronald R. , Hopson Natalie
Published: April 2006

Rats given a choice between a 5% alcohol solution and water will dramatically increase alcohol preference on the days following experience with inescapable electric footshocks, compared with unshocked animals. Although, total alcohol preference did not differ during shock days, an interaction occurred between shock stress and alcohol preference. Rats that initially preferred alcohol decreased alcohol preference during shock days, whereas, rats that initially avoided alcohol increased alcohol preference during shock days. Therefore, the stress of inescapable electric footshock has bidirectional effects on alcohol preference. These bidirectional effects depend on the temporal dynamics of alcohol consumption in relation to the shock experience and the initial alcohol preference.
Comparison of Blood Aldehyde Dehydrogenase Activities in Moist Snuff Users, Cigarette Smokers and Nontobacco Users
Authors: Helander Anders , Curvall Margareta
Published: April 2006

The aldehyde dehydrogenase (ALDH; EC 1.2.1.3) activity was determined in samples of whole blood and in isolated erythrocytes and leukocytes from users of Swedish moist snuff, cigarette smokers and non‐tobacco‐using controls. The mean whole blood ALDH activity of the smokers was reduced by 21% (P<0.001) when compared to the controls, while that of the snuff users was reduced by only 8% (not significant). Similar but somewhat less pronounced differences were obtained both in the assays with erythrocytes and leukocytes. In the cigarette smokers, the whole blood activity correlated significantly (r= ‐0.79, P<0.001) with the plasma concentration of cotinine, the major metabolite of nicotine, whereas no correlation was observed for the users of moist snuff. Similar plasma nicotine and cotinine levels were found in smokers and snuff users, which indicates that the reduced blood ALDH activity in smokers is not caused by nicotine or any of its metabolites, but more likely, by components formed during combustion of tobacco. Since a reduced blood ALDH activity has previously been suggested as an indicator of excessive alcohol consumption, the present results show that, in future studies on blood ALDH, the smoking habits should also be taken into account.
Videotape versus Computer Interactive Education in Alcoholic and Nonalcoholic Controls
Authors: Alterman Arthur I. , Baughman Timothy G.
Published: April 2006

Few studies have evaluated the ability of the alcoholic patient to learn treatment‐related information and all have involved conventional educational modalities such as videotape or lecture. Since computer interactive (Cl) programs allow for individualization, feedback, and active learning, we were interested in determining whether Cl would prove to be a more effective educational/treatment modality for male alcoholic patients than the conventional videotape (V) modality. The current study compared the relative effectiveness of the CI and V educational interventions for VA alcoholic patients and a cognitively and sociodemographically matched sample of nonalcoholic VA patients.

The 91 male alcoholic subjects (46 V, 45 Cl) were lower socioeconomic outpatients in a VA Alcoholism Treatment program. Control subjects were 35 nonalcoholic men (18 V, 17 Cl) attending an outpatient medical clinic at the same facility. All subjects were individually exposed in a single session to a 1 hr intervention on the Medical Effects of Alcohol. Baseline knowledge was measured prior to the intervention using a 21‐item multiple choice test, while learning and retention were assessed with the same instrument 24 hr after the intervention. All four subgroups (two types of subjects x two types of intervention) identified approximately three more items correctly at the post‐test than at baseline. Thus, neither alcoholics for nonalcoholics acquired more information when exposed to the CI intervention. Further, no differences were found overall in the learning of the alcoholic and nonalcoholic subjects. The implications of these findings and their limitations are discussed.
Alcohol Preference and Hepatic Alcohol Dehydrogenase Activity in Adult Long‐Evans Rats is Affected by Intrauterine Sibling Contiguity
Authors: Mankes R. F. , Glick S. D. , Van der Hoeven T. , LeFevre R
Published: April 2006

Alcohol preference and hepatic alcohol dehydrogenase activity in adult rats are known to be sexually dimorphic. Intrauterine sibling contiguity (the intrauterine position of a fetus relative to adjacent siblings of the same or opposite sex) alters selected reproductive, behavioral and enzymatic sexual dimorphisms via intersibling sex hormone transfer. We postulated that sibling contiguity would affect alcohol preference and hepatic alcohol metabolism in adult rats. The results of our study demonstrate that adult mMm male Long–Evans rats (genetic male rat developing in utero between two male siblings) had significantly lower ethanol preference, attained higher blood alcohol levels after standard ethanol “challenge” doses and had significantly lower hepatic alcohol dehydrogenase activity than either male siblings developing in utero between two females (fMf) or genetic females developing between two males or between two females (mFm or fFf). Hepatic cytosolic aldehyde dehydrogenase activity was higher in adult female than male rats regardless of nearest neighbor siblings. It is suggested that the differences in ethanol preference and hepatic alcohol dehydrogenase activity between the adult mMm and fMf male rats is due to differences in prenatal hormonal environment which can modulate sexual dimorphisms in alcohol intake and metabolism in the adult.
Interrelationship between Activation of Dopaminergic Pathways and Cerebrospinal Fluid Concentration of Dopamine Tetrahydroisoquinoline Metabolite Salsolinol in Humans: Preliminary Findings
Authors: Faraj Bahjat A , Camp Vernon M. , Kutner Michael
Published: April 2006

The main objective of this study was to determine whether the activation of dopaminergic pathways, through adrenal‐caudate transplantation, stimulated the production of dopamine and salsolinol in cerebrospinal fluid (CSF) of patients with Parkinson's disease. Dopamine sulfate and salsolinol sulfate in CSF specimens were measured by radioenzymatic technique. The results of this study demonstrated that the replacement of degenerative nigrostriatal neurons with new dopamine‐producing cells by adrenal brain transplants in patients with Parkinson's disease resulted in significant increase (p <0.05) in CSF levels of free dopamine, dopamine sulfate, free salsolinol, and salsolinol sulfate as compared with preoperative levels. Moreover, the oral administration of L‐dopa to these transplanted patients caused substantial (p <0.001) elevation in CSF levels of free dopamine (before L‐dopa, 146 ± 57 pg/ml; after L‐dopa, 575 ± 207 pg/ml), dopamine sulfate (before L‐dopa, 1966 ± 945 pg/ml; after L‐dopa, 41679 ± 29326 pg/ml), free salsolinol (before L‐dopa, 43 ± 29 pg/ml; after L‐dopa, 186 ± 90 pg/ml), and salsolinol sulfate (before L‐dopa, 405 ± 477 pg/ml; after L‐dopa, 2908 ± 2572 pg/ml), respectively.
The Influence of the Renin Gene on Alcohol Consumption in Dahl Rats
Authors: O'Dowd B. F. , Grupp L. A.
Published: April 2006

A rat renin allele (the S‐allele) has been identified in Dahl rats which cosegregates with increases in blood pressure. Rats with a double dose of the allele—the salt‐sensitive hypertensive rats—have low renin activity compared with the salt‐resistant hypertensive rat that does not have this S‐allele. Alcohol consumption in rats has also been shown to vary with renin activity, and the possible involvement of renin activity in the genetics of alcohol consumption was suggested by previous work showing that the alcohol‐preferring P line of selected rats had low renin levels. In the present study we examined alcohol consumption in a group of inbred Dahl rats, which have a double dose of the S renin allele, and in a group of selected Dahl rats, which have only a single dose of this S‐allele. After an initial acclimation period, these two groups were first given daily 1‐hr access to ascending concentrations of alcohol (3%, 6%, 8% w/v) over a 34‐day period followed by continuous access to alcohol for a further 10 days. Water and food were always available. Regardless of whether alcohol was rationed or continuously available, the rats with the double dose of the S‐allele drank significantly more alcohol than the rats that had only a single dose of this allele. These findings suggest that genetically mediated alterations in the renin gene may exert a significant influence on alcohol consumption and may be a component in the etiology of alcoholism.
Chronic Tolerance and Sensitization to Alcohol in Sons of Alcoholics
Authors: Newlin David B. , Thomson James B.
Published: April 2006

In view of conflicting results concerning differences between sons of alcoholics and sons of nonalcoholics in response to a single alcohol challenge (with a given dose), we exposed these high and low risk groups to several sessions in which they drank alcohol at the same dose in order to measure the development of chronic tolerance or sensitization with repeated doses. Sons of alcoholics and sons of nonalcoholics received a moderate dose of alcohol (0.5 g/kg) in three sessions with alcohol, followed by a placebo session. Sons of alcoholics developed reverse tolerance or chronic sensitization to repeated dosings of alcohol in finger pulse amplitude, while sons of nonalcoholics did not. Sons of alcoholics failed to show chronic tolerance in skin conductance and finger temperature, while sons of alcoholics did show the development of tolerance. Sons of alcoholics demonstrated greater motor activity throughout the sessions, both before and after alcohol. These results indicate that high and low risk groups differ in terms of their developmental adaptation to alcohol, as well as in the temperamental trait of behavioral activity.
Reduced Cerebral Grey Matter Observed in Alcoholics Using Magnetic Resonance Imaging
Authors: Jernigan Terry L. , Butters Nelson , DiTraglia Gina , Schafer Kimberly , Smith Tom , Irwin Michael , Grant Igor , Schuckit Marc , Cermak Laird S.
Published: April 2006

Twenty‐eight chronic alcoholics and 36 age‐ and sex‐matched nonalcoholic controls were examined with magnetic resonance imaging and brain morphometric analyses. Results confirmed large increases in subarachnoid cerebrospinal fluid (CSF) volume and mild ventricular enlargement in the alcoholics and revealed associated volume reductions of localized cortical and subcortical cerebral structures. Volume losses in the diencephalon, the caudate nucleus, dorsolateral frontal and parietal cortex, and mesial temporal lobe structures were the most prominent. Significant correlations between increments in cortical and ventricular CSF and decrements in the volume of cortical and subcortical grey matter were noted. Although there was little evidence for relationships between performance on neuropsychological tests and volume of grey matter structures, significant correlations between some cognitive measures and subcortical and cortical fluid volumes were found. The parallels between this pattern of affected structures and recent neuropathological findings are discussed.
Personality Stability and Adolescent Substance Use Behaviors
Authors: Bates Marsha E. , Pandina Robert J.
Published: April 2006

Several personality needs have consistently been identified as placing adolescents at heightened risk for the relatively intensive use of alcohol and other drugs. At the same time, little is known about the natural history of personality change during adolescence as it relates to substance use behaviors. Yet, this question is of clear importance to our understanding of personality risk factors for substance use because personality needs appear less temporally stable during adolescence than later in the life span. In this study, we use prospective longitudinal data to investigate the relation of high‐risk personality needs to substance use in two groups of adolescents: those who maintained a temporally stable personality need structure across 3 years and those who showed considerable changes in personality needs during the same time interval. Subjects were 12, 15, or 18 years old at the first test time and 15, 18, or 21 years old, respectively, at the second test time. For subjects of both sexes, only those who maintained a temporally stable, low‐risk personality profile showed quite conservative substance use patterns across time compared with all others. Generalized personality changes were linked to more intensive substance use behaviors in males, especially among those who had high levels of risky personality needs at the first test time. In contrast, personality change, per se, did not appear as relevant to females’ alcohol and other drug use behaviors until combined with information regarding their level of high‐risk personality needs. The results are discussed in terms of their implications for prevention and future research.
In Vivo Microdialysis Study of Brain Ethanol Concentrations in Rats Following Oral Self‐Administration
Authors: Ferraro Thomas N. , Carrozza David P. , Vogel Wolfgang H.
Published: April 2006

Using intracerebral microdialysis, the time‐course of ethanol absorption was determined in the striatum of rats after oral self‐administration of an ethanol solution. Microdialysis samples were collected every 10 min for 1 hr before and 1 hr after consumption of ethanol over a 5‐min period. Substantial levels of ethanol were detected in the brain in the first sample taken after self‐administration although these levels did not correlate with the amount of ethanol consumed. Striatal ethanol levels reached maximum or near maximum by the second sample and remained constant for the time points between 20 and 60 min; at these times, brain ethanol levels correlated significantly with the amount consumed. This study demonstrates that oral consumption of ethanol leads to measurable brain levels within a relatively short time. Results suggest that experimental animals may experience the central effects of ethanol during the course of drinking and this could play a role in alcohol preference or avoidance behavior.
Suppression of Immune Responsiveness: Sex Differences in Prenatal Ethanol Effects
Authors: Weinberg Joanne , Jerrells Thomas R.
Published: April 2006

Exposure to ethanol in utero results in changes in the offspring's developing immune system, including thymus lymphocyte subpopulation shifts and functional lymphocyte changes that persist in adult animals. The present study was designed to define further the extent of changes in the immune system that result from fetal ethanol exposure and to compare effects in male and female offspring. In adulthood, male and female offspring from Sprague‐Dawley dams fed an ethanol‐containing liquid diet (alcohol, A), an isocaloric liquid control diet (pair‐fed, PF), or laboratory chow and water (control, C) during pregnancy were tested for several measures of immune competency. Prenatal ethanol exposure differentially affected male and female offspring. Fetal ethanol‐exposed males exhibited a decrease in thymocyte number as well as a decreased splenic lyrnphocyte proliferative response to the T‐cell mitogen, concanavalin A (Con A), with a concomitant decrease in recoverable blast cells, when compared with PF and C males. Further, the defect in T‐cell proliferation of A males was not due to an inability to produce the critical growth factor, interleukin‐2 (IL‐2), but to an inability of lymphoblasts to utilize exogenous IL‐2. Fetal ethanol‐exposed females showed some suggestion of lower thymocyte counts and decreased splenic T‐cell proliferative responses to Con A compared to PF and C females. For most of the immune measures, however, no significant differences occurred among A, PF, and C females. In utero ethanol exposure did not significantly alter spleen cell counts or IL‐2 production, splenic B‐cell proliferation to bacterial lipopolysaccharide (LPS), or thymocyte response to IL‐2 in animals of either sex. As expected, however, all females had lower lymphoid organ cell counts and generally better lymphocyte responses than males from the corresponding groups.

These data demonstrate that exposure to ethanol during fetal development results in a number of deficits in immune competency that persist in the adult animal. Of particular importance are the observations that these deficits were observed in T‐cell‐dependent aspects of immunity and were found primarily in male offspring.