bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alcohol Use by Alcoholics with and without a History of Parental alcoholism
Authors: Worobec Thomas G. , Turner Winston M. , O'Farrell Timothy J. , Cutter Henry S. , Bayog Rogelio D. , Tsuang Ming T. 
Published: April 2006

The association between parental history of alcoholism and the nature of alcoholism was assessed using a more reliable measure of family history (Family Tree Questionnaire) and a more comprehensive inventory of alcoholism (Alcohol Use Inventory) than used in earlier studies. Parental alcoholism was associated with more severe alcoholism on most parameters of alcohol use (age of onset, quantity, frequency, preoccupation, and sustained use) and alcohol‐related problems (social, vocational, physical, cognitive, and loss of control). The association between parental history of alcoholism and more severe alcoholism in the probands was independent of age of onset of alcoholism, current age, socioeconomic background, and marital status.Parental history positive (PH+) alcoholics were more reliant on alcohol to manage their moods but did not differ significantly from parental history negative (PH‐) alcoholics in the use of alcohol to improve sociability or mental functioning or to cope with marital problems. Surprisingly, the degree of concern, guilt, and worry over the negative consequences of drinking was not significantly different for PH+ alcoholics although the negative consequences were clearly much more severe for this group. While the data are inconclusive about the reasons for more severe alcoholism in PH+ alcoholics, greater reliance on ethanol to manage moods and a relative insensitivity to negative consequences could theoretically account for the vulnerability to more severe alcoholism found in PH+ alcoholics.
Suppression of Natural Killer Cell Activity by Ethanol Consumption and Food Restriction
Authors: Blank S. E. , Duncan D. A. , Meadows G. G. 
Published: April 2006

Effects of 4‐week food restriction and ethanol consumption on natural killer (NK) cell activity and carcass composition were evaluated. Female, C57BL/6 mice given water (H2O) or ethanol (20% w/v, ETOH) ad libitum were placed in one of three dietary groups: unrestricted (UNR), moderately restricted (MR, 2.2 g/day), or severely restricted (SR, 1.8 g/day).Food restriction alone (MR, SR) significantly reduced body, spleen, and thymus weights; carcass lipid content (SR only); spleen cell number; and baseline and interleukin‐2 (rlL‐2) stimulated NK cell activities. Ethanol consumption was unaffected by food restriction and in restricted mice it did not suppress food intake. Thus, average calories derived from ethanol increased from 30% (UNR) to 40% (SR) with the degree of food restriction in these groups. Mice given ethanol and restricted food intake had at least as heavy or heavier body, spleen, and thymus weights than water‐drinking (H2O) counterparts. Spleen cell number was reduced in ethanol‐consuming (ETOH), food restricted groups compared with UNR H2O control. Baseline NK cell activity was suppressed 50% to 90% in all ETOH and food‐restricted groups. rlL‐2 stimulated NK cell activity was suppressed 18% to 76% in food restricted mice independent of ethanol intake. These results indicate that supplementary ethanol calories did not enhance NK cell activity in UNR ETOH mice, nor did they protect splenic NK cell activity from the suppressant effects of food restriction.Ethanol consumption significantly increased carcass lipid content in all groups compared with their H2O counterparts. This increase was largely responsible for the preservation of body weight in ETOH mice especially during food restriction. Therefore, caution must be exercised when using body weight as an indicator of nutritional status for ETOH mice.
Alcoholic Liver Disease: Pathologic, Pathogenetic and Clinical Aspects
Authors: Ishak Kamal G. , Zimmerman Hyman J. , Ray Mukunda B. 
Published: April 2006

Alcoholic liver disease includes steatosis, alcoholic hepatitis and cirrhosis. Other liver diseases of genetic origin, but with a curious association with alcohol intake, are hemochromatosis and porphyria cutanea tarda. The attribution of chronic hepatitis to alcohol intake remains speculative, and the association may reflect hepatitis C infection. Hepatic injury attributed to alcohol includes the changes reported in the fetal alcohol syndrome.Steatosis, the characteristic consequence of excess alcohol intake, is usually macrovesicular and rarely microvesicular. Acute intrahepatic cholestasis, which in rare instances accompanies steatosis, must be distinguished from other causes of intrahepatic cholestasis (e.g., drug‐induced) and from mechanical obstruction of the intrahepatic bile ducts (e.g., pancreatitis, choledocholithiasis) before being accepted. Alcoholic hepatitis (steatonecrosis) is characterized by a constellation of lesions: steatosis, Mallory bodies (with or without a neutrophilic inflammatory response), megamitochondria, occlusive lesions of terminal hepatic venules, and a lattice‐like pattern of pericellular fibrosis. All these lesions mainly affect zone 3 of the hepatic acinus. Other changes, observed at the ultrastructural level, are of importance in progression of the disease. They include widespread cytoplasmic shedding, and capillarization and defenestration of sinusoids. Progressive fibrosis complicating alcoholic hepatitis eventually leads to cirrhosis that is typically micronodular but can evolve to a mixed or macronodular pattern. Hepatocellular carcinoma occurs in 5 to 15% of patients with alcoholic liver disease.The clinical syndrome of alcoholic liver disease is the result of three factors—parechymal insufficiency, portal hypertension and the clinical consequences of extrahepatic damage produced by alcohol. At the several phases of the life history of alcoholic liver disease, the individual factors play a different role. The clinical manifestations of alcoholic steatosis are mainly extrahepatic in origin. Those of alcoholic hepatitis reflect mainly parenchymal insufficiency and those of cirrhosis are mainly those of portal hypertension.Alcoholic liver injury appears to be generated by the effects of ethanol metabolism and the toxic effects of acetaldehyde, perhaps the immune responses to alcohol‐ or acetaldehyde‐altered proteins, and questionably enhanced by viral hepatitis.Alcoholic hepatitis may be mimicked histologically, and to a varying degree clinically, by a number of conditions (obesity, diabetes, several drug‐induced injuries, jejunoileal bypass, and related “short‐circuiting” of the bowel). Perhaps the most important facet of the hepatotoxicity of alcohol is its enhancement of the effects of a number of other hepatotoxic agents, among which acetaminophen in the example.
Acute in Vivo Effects of Low Ethanol Concentration on the Capacity of Urea Synthesis in Rats
Authors: Jensen Søren Astrup , Almdal Thomas Peter , Vilstrup Hendrik 
Published: April 2006

We studied the effect of acute exposure, by constant intravenous infusion, to a low blood ethanol concentration (range 8‐14 mmol/l) on the in vivo capacity of urea‐N synthesis (CUNS), alanine elimination, and the nitrogen retention in fed and fasted rats. Alanine was infused to obtain a constant blood concentration of a‐amino nitrogen between 7.3 and 11.7 mmol/1, at which concentrations urea synthesis is at maximum.CUNS was calculated after nephrectomy as accumulation of urea in body water, elimination of alanine as alanine infusion rate corrected for accumulation, and nitrogen retention as the difference.In the fed state ethanol decreased CUNS from 7.84 ± 0.32 μmol N/(min 100 g body weight (BW)) (mean ± SEM) (n = 7) to 6.30 ± 0.58 (n = 6) (p <0.001) and in the fasted state from 8.25 ± 0.27 μmol N/ (min 100 g BW) (n = 10) to 6.90 ± 0.25 (n = 10) (p <0.001).In the fed state ethanol increased the elimination of alanine from 6.49 ± 0.28 μmol/ (min 100 g BW) (n = 7) to 6.95 ± 0.25 (n = 6) (p <0.01), and in the fasted state decreased it from 6.25 ± 0.12 μmol/ (min 100 g BW) (n = 10) to 5.67 ± 0.20 (n = 10) (p <.001).In the fed state nitrogen retention was changed by ethanol from‐1.35 ± 0.53 μmol/ (min 100 g BW) (n = 6) to 0.65 ± 0.77 μmol/(min 100 g BW) (n = 7) (p <0.001), and in the fasted state from‐2.0 ± 0.27 μmol/(min 100 g BW) (n = 10) to‐1.23 ± 0.30 μmol/(min 100 g BW) (n = 10) (p <0.001).The effects of acute exposure to low ethanol concentration on CUNS and nitrogen retention were abolished in rats pretreated with methylene blue.It is concluded that acute exposure to low ethanol concentrations transiently leads to suppression of the capacity of urea synthesis, presumably due to the decrease in NAD/NADH ratio during metabolism of ethanol.
Acetaldehyde Metabolism in Different Aldehyde Dehydrogenase‐2 Genotypes
Authors: Enomoto Nobuyuki , Takase Shujiro , Yasuhara Minoru , Takada Akira 
Published: April 2006

In order to clarify the relationships between acetaldehyde (Ac‐CHO) metabolism and low Km (mitochondrial) aldehyde dehydrogenase (ALDHP) genotypes, hepatic ALDHS activity was determined and serial changes of blood Ac‐CHO levels after ethanol administration were analyzed in the individuals homorygous for the normal ALDH2 genes, heterozygous for the normal and mutant ALDH2 genes, and homozygous for the mutant ALDH2 genes. Genomic DNA was extracted from white blood cells and genotyping of ALDH2 was performed using the polymerase chain reaction technique and slot blot hybridization with synthesized oligonucleotide probes specific to the normal and mutant ALDH2 genes.ALDH2 activity was not detectable in the liver in two cases of the mutant homozygote. In four out of eight cases of the heterozygote, hepatic ALDH2 activity was measurable, although the activity was lower compared with that in the normal homozygote. Blood ethanol levels after alcohol administration were not different among the three different ALDH2 genotypes. Blood Ac‐CHO levels after drinking of alcohol were significantly higher in the heterorygotes and the mutant homozygotes than in the normal homozygotes. The levels after a moderate amount of ethanol (0.8 g/kg of body weight) in a case of the mutant homozygote were not different from those of the heterozygotes. However, the levels after a small amount of ethanol (0.1 g/ kg of body weight) were significantly higher in the mutant homorygotes than in the heterozygotes.These results indicate that hepatic ALDH2 activity is lacking completely, and metabolism of Ac‐CHO in the liver is severely impaired in the homozygotes of the mutant ALDH2 genes. On the other hand, the lack of hepatic ALDH2 activity is partial, and impairment of hepatic Ac‐CHO metabolism is mild, in the heterozygotes of the ALDH2 genes. Clear differences of blood Ac‐CHO levels after a small amount of ethanol suggest that blood Ac‐CHO levels after a small amount of ethanol are good markers for the evaluation of ALDH2 genotypes.
Effects of in Utero Ethanol Exposure on the Developing Serotonergic System
Authors: Druse Mary J. , Kuo Alison , Tajuddin Nuzhath 
Published: April 2006

Previous work in this laboratory demonstrated that the 19‐ and 35‐day‐old offspring of ethanol‐fed rats have a significant deficiency of cortical serotonin (5‐HT) and 5‐hydroxyindoleacetic acid (5‐HIAA), as well as a decrease in the number of total 5‐HT1 receptors in the motor and somatosensory cortex. The present studies extend our previous reports by demonstrating that there is also a deficit of 5‐HT and 5‐HIAA in the motor cortex but not in the somatosensory cortex. In addition, we have shown that a deficit of 5‐HTlA receptors in the motor and somatosensory cortices contributes to the deficit of total 5‐HT1 receptors. In contrast, we did not observe any changes in the binding to 5‐HT1B receptors in these cortical regions from the 19‐day‐old offspring of ethanol‐fed rats.The present studies also examined the effects of in utero ethanol exposure on the early development of the serotonergic system. The results of these studies demonstrated a deficit of 5‐HT and/or 5‐HlAA in the brain stem as early as the 15th day of gestation (G15) and in the cortex as early as G19. In addition, we demonstrated a delay in both the normal developmental decline of 5‐HT1A receptors in the brain stem and in the acquisition of cortical 5‐HT1A receptors. No changes were found in the binding of [125]cyanopindolol to 5‐HT1B receptors in either region of fetal or neonatal rats exposed to ethanol in utero. Given the important role of serotonin for normal central nervous system (CNS) development, it is possible that these early serotonergic abnormalities contribute to altered CNS development in ethanol‐exposed rats.
Effect of Concentration of Ingested Ethanol on Blood Alcohol Levels
Authors: Roine Risto P. , Gentry R. Thomas , Lim Robert T. , Baraona Enrique , Lieber Charles S. 
Published: April 2006

The effect of the concentration of ingested ethanol on the resulting blood alcohol concentrations (BAC) was tested in both humans and rats. In humans, when 0.3 g/kg body weight ethanol was ingested postprandially, the mean area under the blood alcohol curve (AUC) and the mean peak BAC were significantly lower with a concentrated (40% w/v) than with a dilute (4%) solution. Similarly, rats in the fed state exhibited decreasing mean AUCs with increasing concentrations (4%, 16%, and 40%) of intragastrically administered ethanol (1.0 g/kg). Pharmacokinetic analysis comparing intragastric and intraperitoneal administration of ethanol to rats indicated that the more concentrated solution resulted in less alcohol reaching the systemic circulation (4%: 0.896 ± 0.071 g/kg; 16%: 0.772 ± 0.072 g/kg; 40%: 0.453 ± 0.037 g/kg) and suggested that this effect could be attributed to two factors: increased gastric retention of ethanol (4%: 0.109 ± 0.024 g/kg; 16%: 0.102 2 0.016 g/kg; 40%: 0.214 ± 0.042 g/kg) and a large increase in first‐pass metabolism (4%: 0.004 ± 0.054 g/kg; 16%: 0.145 ± 0.048 g/kg; 40%: 0.329 ± 0.044 g/kg).In contrast to the results in the fed state, in humans fasted overnight the concentration of alcohol consumed (4%, 16%, and 40%) had no significant effect on mean AUCs. In fasted rats, mean AUCs after intragastric intubation of the two lower concentrations of ethanol (4% and 16%) were comparable to those found after intraperitoneal injection, and only the highest ethanol concentration (40%) produced a lower mean AUC.Our results demonstrate that the consumption of a concentrated solution of ethanol results in lower blood alcohol levels than does a dilute solution, when subjects are tested in the fed state. This effect is associated with more first pass metabolism and less bioavailability with the high ethanol concentrations. These findings now raise the issue whether ethanol in low concentration beverages such as beer and wine has a greater bioavailability than in distilled spirits.
Carbohydrate‐Deficient Transferrin (CDT) in Serum as a Possible Indicator of Heavy Drinking in Young University Students
Authors: Nyström Mikael , Perasalo Juhani , Salaspuro Mikko 
Published: April 2006

Carbohydrate‐deficient transferrin (CDT) in serum was studied as a possible marker of heavy drinking in a sample of 187 female and 102 male 1st year university students from Finland. CDT was measured by a new radioimmunoassay (Pharmacia CDT RIA). Alcohol consumption was measured on a quantity‐frequency scale.For female students CDT was 18.2 ± 0.45 units/liter (mean ± SEM) and for male students 13.3 ± 0.48 units/liter. 9.6% of female students and 7.8% of male students had elevated CDT with a cutoff level of 26 units/liter for females and 20 units/liter for males. The correlation between CDT and reported alcohol consumption was 0.30 (p < 0.001) for females and 0.25 (p= 0.014) for males. Those reporting a consumption of at least 10 kg of pure ethanol per year were considered as heavy drinkers (3.7% of females and 22.5% of males). In female students the average CDT of heavy drinkers did not differ significantly from that of social drinkers but in teetotalers CDT was significantly (p < 0.03) lower than in female alcohol users. In male students the average CDT of heavy drinkers was higher than the average of social drinkers (p < 0.1) and significantly higher than the average of teetotalers (p < 0.001). In the detection of heavy drinking among male students elevated CDT had a specificity of 96.2% and a sensitivity of 21.7%. None of the seven heavy drinking female students had an elevated CDT.As compared with the other laboratory markers of alcoholism (gamma glutamyltransferase, mean corpuscular volume, and highdensity lipoprotein cholesterol, and β‐hexosaminidase), which in this student population have been proven to be unspecific indicators of heaving drinking, CDT had a better correlation to reported drinking.
Tumor Necrosis Factor in Alcohol Enhanced Endotoxin Liver Injury
Authors: Honchel Ronald , Ray Mukunda B. , Marsano Luis , Cohen Donald , Lee Eun , Shedlofsky Steven , McClain Craig J. 
Published: April 2006

Endotoxin administration causes liver injury. Patients with alcoholic liver disease frequently have portal vein and systemic endotoxemia, and some investigators have suggested that endotoxin plays an etiologic role in alcoholic liver injury. Many of the metabolic effects of endotoxin are mediated by the cytokine tumor necrosis factor (TNF). It was the purpose of this study to determine whether TNF plays a role in ethanol‐enhanced endotoxin liver injury. Rats were fed either a diet in which 36% of the calories were from ethanol or an isocaloric control diet. After 6 weeks, groups of 10 rats were intravenously injected with either saline, 1 mg/kg endotoxin, or 30 μg/kg of a prostaglandin E1 (PGE1) analogue + 1 mg/kg endotoxin 24 hr prior to sacrifice. Ethanol/endotoxin‐treated rats had significantly higher liver enzyme levels (ALT 1064 ± 355 IU/liter, AST 2024 ± 515 IU/liter) compared with isocaloric/endotoxin controls (ALT 237 ± 54 IU/liter, AST 602 ± 80 IU/liter). Ethanol/endotoxin rats also had significantly higher peak serum TNF concentrations (992 ± 200 units/ml) compared with isocaloric/endotoxin controls (344 ± 96 units/ml). Pretreatment of ethanol/endotoxin rats with PGE1 caused significant attenuation of liver injury (ALT: 267 ± 64 IU/liter, AST 612 ± 77 IU/liter) and a diminished serum TNF response. In contrast to chronic ethanol administration, acute gavage with 2 mg/kg ethanol (30% w/v) followed by intravenous injection of 2 mg/ kg endotoxin produced significantly lower peak serum TNF concentrations (401 ± 76 units/ml) than gavage with distilled water (1152 ± 208 units/ml).We conclude that chronic ethanol feeding enhances endotoxin‐stimulated peak serum TNF concentrations, endotoxin liver injury, and pretreatment with the TNF synthesis inhibitor PGE1 attenuates this liver injury. Furthermore, acute and chronic alcohol feeding appear to have opposite effects on endotoxin stimulated serum TNF levels.
The Effects of Maternal Ethanol Consumption on Lactational Transfer of Immunity to Trichinella spiralis in Rats
Authors: Steven William M. , Stewart George L. , Seelig Leonard L. 
Published: April 2006

Transient immunity to the intestinal parasite Trichinella spiralis can be transferred from the mother to the neonate during lactation. The goal of this study was to determine whether maternal ingestion of ethanol during pregnancy and lactation inhibited expression of anti‐T. spiralis immunity in nursing pups. Groups of female rats were infected with 1000 T. spiralis L1 larva, mated, and fed either ethanol‐containing or isocaloric liquid diets and maintained on diets through pregnancy and lactation or were fed the liquid diets for 30 days before T. spiralis infection, mated, and maintained on diets through pregnancy and lactation. Pups were challenged orally with 200 T. spiralis larva at 14 days postdelivery (preweaning period) or 21 days postdelivery (postweaning period) and were sacrificed either 3 or 8 days after respective challenge. Intestinal worm counts and serum titers of anti‐T. spiralis IgG antibodies were determined for each pup. No difference in the number of intestinal worms between pups of ethanol‐treated and pair‐fed dams that received ethanol diet after T. spiralis infection was observed in the preweaning period. This was also true of pups from the dams sacrificed at 3 days after challenge in the postweaning period. However, similar pups sacrificed at 8 days after challenge showed significantly higher worm counts (decreased immunity) relative to their pair‐fed controls. Pups of dams that received ethanol containing diet 30 days prior to T. spiralis‐infection showed significantly higher numbers of intestinal worms relative to pair‐fed pups at both the preweaning and postweaning periods.The dams receiving ethanol after T. spiralis‐infection and their pups showed significantly lower titers of specific IgG antibodies than pups of pair‐fed control animals during the preweaning period. Dams fed ethanol diet prior to T. spiralis‐infection and their suckling pups were not different from pair‐fed animals in serum IgG antibody levels at the preweaning or postweaning period. These results showed that maternal ethanol consumption can adversely influence the transfer of lactational immunity to T. spiralis in suckling neonates. This effect was greatest when ethanol was administered to the dam prior to infection of the dam with T. spiralis. The depression of lactational immunity was not completely related to alterations in specific anti‐bodies but could be associated with defects in Cell mediated immune responses.
Lactation and Prolactin Release in Foster Dams Suckling Prenatally Ethanol Exposed Pups
Authors: Subramanian Marappa G. 
Published: April 2006

The effect of prenatal ethanol exposure on lactation was studied employing prenatally ethanol‐exposed pups transferred to foster dams following parturition. During pregnancy, from day 8 to term, dams consumed either standard laboratory chow (ad libitum control), or liquid diets containing 0%, 17.5%, or 35% ethanol derived calories (EDC). To equilize caloric intake, the 0% and 17.5% EDC groups were pair‐fed to rats in 35% EDC group. Following delivery, pups born to dams fed with laboratory chow (control) or liquid diets containing 0, 17.5, or 35% EDC were adjusted to eight per litter and transferred to foster dams, which had been fed laboratory chow and water ad libitum throughout pregnancy. Foster dams were implanted with an atrial catheter on day 3 of lactation. On days 6 (early lactation) and 10 (midlactation), following separation of litters from dams for a 6‐hr period, a baseline blood sample was removed via a catheter extension. Pups were weighed and returned to the dams. Subsequent blood samples were obtained 10, 30, 60, 120, and 180 min after initiation of suckling. Suckling latency and the amount of milk consumed during the 3‐hr suckling were also determined. Litters were weighed on days 2, 6, 10, and 21.The prolactin surge in foster dams in response to suckling by prenatally ethanol‐exposed pups was not altered on day 6 of lactation. On day 10, after the initial rise, suckling‐induced prolactin was amplified in dams suckled by prenatally ethanol‐exposed pups. This may be due to either a compensatory neuroendocrine mechanism in the foster dams for adequate milk secretion in response to the poor suckling or to the shorter but more frequent suckling episodes by prenatally ethanol‐exposed pups. On day 6 suckling latency for the 35% EDC group was greater compared to control and 17.5% EDC groups and the amount of milk consumed was lower for this group on both days 6 and 10. Pups prenatally exposed to 35% EDC diet weighed less up to weaning. These results demonstrate the continued nursing difficulty experienced by offspring and the persistence of suckling‐deficits in pups caused by prenatal ethanol exposure.