bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study of Cytochrome P4502E1 mRNA Level of Mononuclear Cells in Patients With Alcoholic Liver Disease
Authors: Yano Hirokazu , Tsutsumi Mikihiro , Fukura Masayuki , Chen Wun‐Bil , Shimanaka Koshi , Tsuchishima Mutsumi , Takase Shujiro , Imaoka Susumu , Funae Yoshihiko 
Published: April 2006

Background: Cytochrome P‐4502E1 (CYP2E1) is an important enzyme because of its unique ability to convert many substrates to cytotoxins. The increased production of reactive intermediates by elevated enzyme concentrations leads to various pathological conditions. Therefore, it is important to detect induced CYP2E1 levels in alcoholic individuals to avoid xenobiotic‐promoted liver injury. In the present investigation, we detected CYP2E1 mRNA levels of mononuclear cells obtained from 10 ml of blood by using competitive polymerase chain reaction (PCR) method.Methods: Mononuclear cells were obtained from healthy individuals who did and did not drink habitually and patients with alcoholic liver disease (ALD). Complementary DNA synthesis was performed with RNA obtained from mononuclear cells by reverse transcription‐PCR. Competitive PCR of CYP2E1 was performed with the sense (5′‐CTGCAACGTCATA‐GCCGACA‐3′) and antisense (5′‐TCCATTTCCACGAGCAGGCA‐3′) primer and competitor DNA. Competitive PCR of β‐actin also was performed. Electrophoresis was scanned, and each band was digitized. The concentration of CYP2E1 and β‐actin mRNA was calculated from the ratio of competitor DNA.Results: In healthy individuals who did and did not drink habitually, CYP2E1 mRNA levels were 103.3 copies/μl RNA and 101.7 copies/μl RNA, respectively. In actively drinking patients with ALD, CYP2E1 mRNA levels were 103.5 copies/μl RNA, but those levels decreased to 101.7 copies/μl RNA after 4 days of abstinence. No significant difference was observed in CYP2E1 mRNA levels between alcoholic fibrosis and cirrhosis. As control, we measured β‐actin mRNA levels in mononuclear cells in all samples. The mean value of β‐actin mRNA was 104.3 copies/μl RNA in all cases, which included patients with ALD.Conclusions: The results demonstrated that it is possible to measure the CYP2E1 mRNA levels of mononuclear cells in a 10 ml blood sample. The CYP2E1 mRNA level in mononuclear cells increases during drinking and decreases in abstinence for a short period of 3 to 4 days. It is concluded that CYP2E1 mRNA level may be used as an effective marker for alcoholic intake.
Polymorphism of Tumor Necrosis Factor‐β and Alcohol Dehydrogenase Genes and Alcoholic Brain Atrophy in Japanese Patients
Authors: Yamauchi Masayoshi , Takamatsu Masashi , Maezawa Yoshihiko , Takagi Masaru , Araki Takashi , Satoh Shunnya , Toda Gotaro , Saito Saburo 
Published: April 2006

Background: Alcohol abuse can induce brain atrophy, but it only occurs in some alcoholics. Many inflammatory cytokines such as tumor necrosis factor (TNF) are produced rapidly in the brain by experimental or clinical injury.Method: To investigate whether genetic polymorphism of TNF was related to alcoholic brain atrophy, we determined restriction fragment‐length polymorphisms of the TNF‐β genes in 72 male alcoholics. Computed tomography was used to determine the severity of brain atrophy.Results: Digestion with Nco I and Msp I after polymerase chain reaction amplification showed that the TNFB1 allele frequency was significantly higher in patients with brain atrophy than in those without brain atrophy (χ2= 10.20, p= 0.0034). A multivariate analysis that included age, total alcohol intake, ADH2 genotype, and TNF‐β genotype showed that the ADH21/21 genotype and TNFB1/B1 genotype are independently associated with alcoholic brain atrophy. These findings suggest that the TNFB1 allele may be associated with alcoholic brain atrophy.
Alcohol Dehydrogenase Activities in the Human Gastric Mucosa: Effects of Helicobacter pylori Infection, Sex, Age, and the Part of the Stomach
Authors: Matsumoto Michinaga , Yokoyama Hirokazu , Shiraishi Haruko , Suzuki Hidekazu , Kato Shinzo , Miura Souichiro , Ishii Hiromasa 
Published: April 2006

Background: Human gastric mucosa contains three alcohol dehydrogenase (ADH) isozymes (classes I, III, and IV). Various factors such as Helicobacter pylori infection, sex, age, and the part of the stomach involved have been suggested to affect alcohol dehydrogenase activities, although these views are controversial. In this study, these unsettled issues were reexamined.Methods: Activities of class I and IV ADHs were evaluated in the cytosolic fraction of human gastric mucosa samples by reduction of their preferred substrates, namely acetaldehyde and m‐nitrobenzaldehyde, and activities of class III were evaluated by oxidation of its preferred substrate, formaldehyde. Then, effects of Helicobacter pylori infection, sex, age, and the part of the stomach involved were examined.Results: Class I, III, and IV ADH activities were 17.5 ± 8.4, 4.2 ± 2.5, and 8.9 ± 3.9 nmol of nicotinamide adenine dinucleotide oxidation per minute per milligram of protein, respectively, for the entire population. Helicobacter pylori infection significantly reduced class I and IV ADH activities but did not affect activity of class III. In the samples without Helicobacter pylori infection and severe gastritis, sex did not affect class I, III, or IV ADH activities. In the same series, class IV ADH activity significantly decreased with age (p= 0.006), whereas no correlation was found between age and ADH activity of class I and III ADHs. The level of class IV ADH activity was significantly higher in the upper body than in the lower regions, whereas no such heterogeneity was observed in class I and III ADH.Conclusions: Various factors affect human gastric ADH activities, such that careful interpretation of their significance is necessary.
Electroacupuncture Stimulation Suppresses the Increase in Alcohol‐Drinking Behavior in Restricted Rats
Authors: Yoshimoto K. , Kato B. , Sakai K. , Shibata M. , Yano T. , Yasuhara M. 
Published: April 2006

Background: Although a number of studies on traditional eastern or Chinese medicine, such as acupuncture, moxibustion, and herbal drugs, have been reported, few reports describe electroacupuncture (EAC) effects on drug‐ and alcohol‐seeking behaviors in animal models. The purpose of the present study was to investigate the effect of EAC on changes in alcohol‐drinking behavior in rats challenged with restriction and immobilization stress.Material and Methods : Male Sprague Dawley® rats (260–280 g) were tightly hung and immobilized in restriction models for 10 min. These immobilization stresses were performed twice a week for 1 week and for 3 consecutive weeks for the short‐ and long‐restricted stress groups, respectively. EAC was applied for 10 min to the hindlimb point, Tsu‐San‐Li (ST 36), and the lumbar point, Shen‐Shu (BL 23). These points are used to treat mental and psychosomatic disorders and are known clinically to produce a sedation effect. Time‐access alcohol‐drinking behavior was determined at 24 hr after the termination of EAC. Finally, brain dopamine (DA) levels were assayed in the two groups. A sham‐control group underwent only restricted stress without EAC.Results: Time‐access alcohol‐drinking behavior increased significantly in the long‐restricted group compared with the short‐restricted group and controls. EAC applied to the ST 36 (Tsu‐San‐Li) point suppressed the increased alcohol‐drinking behavior in restricted rats. However, EAC applied to the Shen‐Shu (BL 23) point was not effective, because alcohol‐drinking behavior was significantly increased in long‐restricted rats compared with short‐restricted rats. Striatal DA levels of restricted rats with EAC stimulated at Tsu‐San‐Li were increased significantly compared with the rats with EAC applied to the Shen‐Shu point.Conclusion: These findings suggest that EAC applied at ST 36 (Tsu‐San‐Li) was more effective for reducing the increased alcohol‐drinking behavior in restricted rats, and they showed that a point specific in EAC procedure was associated with an increase of striatal DA levels. These findings provide new information for understanding alcohol‐drinking behavior and for treating human alcoholics.
A Clinicopathological Study of Acute Hepatitis in Heavy Drinkers, Unrelated to Hepatitis A, B, or C Viruses
Authors: Miyano Shintaro , Maeyama Shiro , Iwaba Akiko , Ogata Seiichirou , Koike Junki , Kishi Masaya , Uchikoshi Toshiyuki 
Published: April 2006

Background: There are six histological classifications of alcoholic liver disease (ALD) in Japan. However, it is unclear whether all cases of the disease conform to these criteria. This study investigated the clinicopathological features of eight histologically unusual cases of ALD.Methods: The characteristic features of alcohol drinking behavior, subjective and objective symptoms, laboratory data on admission, and progress after admission were analyzed for eight patients with acute‐onset hepatitis.Result: The eight patients showed histologically acute hepatitis, with much spotty necrosis that contained granular ceroid pigment by Kupffer cells, which indicated acute parenchymal damage of the liver, but with no Mallory bodies and unremarkable intrasinusoidal neutrophilic infiltration. The only etiological factor for all the cases was habitual alcohol consumption, with increased consumption just before the onset of symptoms. In five cases that were tested, the patients were negative for hepatic viral markers, which included hepatitis G virus RNA and TT virus DNA.Conclusion: Some cases of ALD may not conform to the current histological classifications in either Japan or Western countries. It seems natural to consider that these cases are developed by other, unknown causes that overlap with ALD rather than as a result of damage from alcoholic overload.
Inverse Genetic Association Between Alcohol Preference and Severity of Alcohol Withdrawal in Two Sets of Rat Lines Selected for the Same Phenotype
Authors: Chester J. A. , Price C. S. , Froehlich J. C. 
Published: April 2006

Background: The purpose of the present study was to determine whether alcohol‐naïve rats selectively bred for alcohol preference or nonpreference differ in alcohol withdrawal severity using two sets of rat lines selectively bred for the same phenotype.Methods: Alcohol‐naïve male rats from the high alcohol drinking (HAD1) and low alcohol drinking (LAD1) rat lines and from the alcohol preferring (P) and nonpreferring (NP) rat lines received an intragastric infusion of alcohol (4.0 g/20.3 ml/kg; 25% v/v) or an equal volume of water once a day for 10 consecutive days. Alcohol withdrawal severity was assessed at using a behavioral rating scale and a radiant heat assay measured analgesia at 10, 12, 14, 16, 18, and 24 hrs following infusion of alcohol or water on days 1, 5, and 10 of treatment.Results: Data were analyzed using body weight as a co‐factor to correct for differences in body weight between the HAD1/LAD1 and P/NP lines. Acute (1 day) but not repeated alcohol treatment (5 or 10 days) produced mild behavioral signs of withdrawal in LAD1 but not in HAD1 rats. HAD1 and LAD1 rats showed alcohol‐induced analgesia after 1 and 5 days of alcohol treatment that disappeared by day 10 in both lines. Repeated alcohol treatment (5 days) produced mild behavioral signs of withdrawal in NP but not in P rats. Neither P nor NP rats showed alcohol‐induced analgesia after 1, 5, or 10 days of alcohol treatment.Conclusions: An inverse genetic association was found between alcohol preference and severity of alcohol withdrawal in two sets of rat lines selected for the same phenotype. The pattern of alcohol withdrawal that emerged over the course of the 10 days of alcohol treatment differed between the two lines selected for low alcohol drinking (LAD1 and NP), suggesting that unique sets of genes may influence alcohol withdrawal severity in the two lines.
The Alcohol Use Disorders Identification Test and Carbohydrate‐Deficient Transferrin in Alcohol‐Related Sickness Absence
Authors: Hermansson Ulric , Helander Anders , Brandt Lena , Huss Anders , Rönnberg Sten 
Published: April 2006

Background: Previous studies have shown that elevated, risky levels of alcohol consumption may lead to higher rates of sickness absence. However, no studies have examined the Alcohol Use Disorders Identification Test (AUDIT) or serum carbohydrate‐deficient transferrin (CDT) in relation to sickness absence in the workplace. The purpose of this study was to examine the relationship between sick‐days, 12 months before screening, and the AUDIT and CDT (CDTect kit). Serum γ‐glutamyltransferase also was used for comparison.Method: The study was carried out over 36 months in a large workplace and formed part of an ongoing controlled study. In conjunction with a routine health examination, employees were offered the opportunity to undergo an alcohol screening. Absence data were obtained from the company payroll system, and sickness absence was analyzed by using a three‐ordinal level cumulative logistic model on the number of sick‐days. Odds ratios (OR) and 95% confidence intervals (CI) are reported.Results: Of the 989 subjects who participated in the study, 193 (19.5%) screened positive in relation to either the AUDIT (≥8 points) or CDT (<20 units/liter for men, and <27 units/liter for women), or both. Employees who screened positive with the AUDIT had a significantly higher proportion of sick‐days (p= 0.047) compared with those who screened negative (OR = 1.4, CI 1.0–1.9). Neither long, continuous periods of sickness absence nor absence on Mondays or Fridays gave a clear indication of individuals who screened positive on the AUDIT or CDT test.Conclusion: Our data indicate that individuals with moderately elevated or risky levels of alcohol consumption show an increase in sick‐days. Accordingly, workplaces have a good reason for using a more systematic approach to alcohol screening in routine workplace health examinations.
Fetal and Maternal Thyroid Hormone Responses to Ethanol Exposure During the Third Trimester Equivalent of Gestation in Sheep
Authors: Cudd Timothy A. , Chen Wei‐Jung A. , West James R. 
Published: April 2006

Background: Abnormal thyroid hormone system function in the mother or fetus during pregnancy can result in brain defects, some of which resemble those found in children with fetal alcohol syndrome. It has been hypothesized that ethanol may act to mediate alcohol‐related birth defects in part by altering thyroid hormone system function. We investigated whether a binge pattern of maternal ethanol consumption over the last trimester equivalent of gestation in sheep results in an alteration in fetal or maternal thyroid function.Methods: Pregnant ewes received saline or ethanol beginning on day 109 of gestation (term, 145 days) for three consecutive days per week followed by 4 days without exposure. The fetuses were surgically instrumented on day 113, and experiments were performed on days 118 or 132. Fetal and maternal blood samples were collected, and plasma tri‐iodothyronine (T3), thyroxine (T4), and free T4 concentrations were measured.Results: Fetal T3 and T4 on day 118, fetal T3 on day 132, and maternal T3 on day 132 were lower in response to ethanol. Fetal and maternal free T4 and maternal T4 did not change in response to ethanol. Fetal thymus and adrenal weights were reduced in response to ethanol.Conclusions: We conclude that, in sheep, maternal ethanol exposure during the third trimester equivalent resulting in blood ethanol concentrations that are commonly achieved by ethanol abusers decreases circulating thyroid hormone concentrations in the mother and fetus and fetal thyroid and thymus mass.
Selective and Enduring Deficits in Spatial Learning After Limited Neonatal Binge Alcohol Exposure in Male Rats
Authors: Johnson Timothy B. , Goodlett Charles R. 
Published: April 2006

Background: In rats, heavy bingelike alcohol exposure during the neonatal brain growth spurt [postnatal days (PD) 4–9] can impair development of spatial learning. This study tested whether binge exposure limited to the latter half of this period (PD 7–9) produced selective spatial learning deficits that endured into adulthood.Methods: On PD 7 to 9, Long‐Evans rats were given intubations of alcohol (5.25 g/kg/day), sham intubations, or no intubations. Rats were tested as adults (≥PD 70) in the Morris water maze under one of three different conditions: place (submerged escape platform in the same location each trial), random (submerged platform in a different, random location each trial), or redundant (visible platform that protruded above the water, in the same location for each trial). A 60‐sec probe trial (with no platform present) followed the last acquisition trial.Results: The mean peak blood alcohol concentration was 401 mg/dl on PD 7. Neonatal alcohol treatment significantly impaired acquisition and reduced place biases on the probe trial in place‐trained males, but not females. Neonatal alcohol treatment had no significant effects on acquisition performance of the random or redundant groups. Redundant training yielded rapid acquisition for all groups. The visible cue overshadowed place cues for all treatment groups, but small place biases were evident in controls. After random training, no group showed place biases.Conclusions: Heavy alcohol exposure in rats limited to the last half of the neonatal brain growth spurt caused enduring deficits in spatial learning, but only in males. The deficits were specific to place learning in the Morris water maze and emerged only when learning and performance depended on the use of distal place cues.
Chronic Effects of Prepubertal Ethanol Administration on Steroidogenic Acute Regulatory Protein in the Rat Ovary
Authors: Srivastava Vinod K. , Hiney Jill K. , Dearth Robert K. , Les Dees W. 
Published: April 2006

Background: A mitochondrial protein, steroidogenic acute regulatory protein (StAR), plays an essential role in steroidogenesis by facilitating delivery of cholesterol across the mitochondrial membrane. Because ethanol (EtOH) causes suppressed estradiol (E2) secretion in prepubertal female rats and rhesus monkeys, we evaluated the effects of chronic EtOH administration on prepubertal ovarian StAR.Methods: Rats were implanted with a gastric cannula on day 24 and began receiving control or EtOH diets on day 28. At 0800 hr on day 33, the experimental groups were subdivided. Half of the EtOH‐treated animals received a subcutaneous injection of pregnant mare serum gonadotropin (PMSG; 15 IU), and the other half received an injection of saline. The chow‐fed and liquid‐diet control groups were also subdivided, with half receiving the PMSG and the other half receiving saline. Eight hours after the respective injections, the animals were killed, and their ovaries and blood were collected.Results: The ovaries from EtOH‐treated rats showed decreased basal expression of both the 3.8‐kb (p < 0.05) and 1.7‐kb (p < 0.01) StAR transcripts. PMSG‐stimulated animals not exposed to EtOH showed a more than 2‐fold increase (p < 0.01) in the ovarian levels of both transcripts. Western blot analysis revealed that EtOH exposure decreased (p < 0.001) the basal expression of StAR protein, which paralleled the decrease in basal StAR messenger RNA. PMSG induced an increase (p < 0.001) in the levels of StAR protein, and this effect was blunted (p < 0.01) by EtOH. These changes observed in ovarian StAR protein were paralleled by decreases in serum pregnenolone and E2.Conclusions: These results demonstrate for the first time that ovarian StAR is a target for the chronic action of EtOH to alter prepubertal steroidogenesis, resulting in suppressed serum E2 secretion during a critical time of development.
Possible Pleiotropic Effects of Genes Specifying Sedative/Hypnotic Sensitivity to Ethanol on Other Alcohol‐Related Traits
Authors: Owens Jeremy C. , Bennett Beth , Johnson Thomas E. 
Published: April 2006

Background Initial sensitivity to ethanol is a predictor of alcohol abuse that has been studied extensively in both human and animal populations. Selection for initial sensitivity to the sedative/hypnotic effects of ethanol resulted in the long‐sleep and short‐sleep lines of mice. Some of the genes selected in these lines could also specify differential responses in other ethanol‐related phenotypes and, perhaps, for other drugs of abuse. We assessed congenic mice carrying a single quantitative trait locus (QTL) from the inbred long‐sleep (ILS) or inbred short‐sleep (ISS) strain on the reciprocal background for a number of ethanol‐ and pentobarbital‐related phenotypes.Methods Each congenic strain was tested for ethanol elimination rates at 4.1 g/kg, ethanol‐induced ataxia at 2.0 g/kg, ethanol‐induced hypothermia at 4.1 g/kg, and pentobarbital‐induced loss of righting reflex (LORR) at 60 mg/kg. Additionally, the ILS.ISS congenics were tested for low‐dose ethanol‐induced activation (LDA) at five doses ranging from 0.6 to 1.2 g/kg ethanol, and the ISS.ILS congenics were tested for LDA at 1.8 g/kg of ethanol.Results There was little difference in the ethanol elimination rate between congenics and background strains, although a modest sex effect was found, with the females eliminating ethanol more rapidly than the males. We were unable to replicate previous differences found in LDA for the Lore1 congenic on the ISS background, because none of the congenics differed from controls for LDA. Lore5 congenics showed a differential effect of pentobarbital‐induced LORR in the expected directions. The Lore1 congenics on the ISS background showed more ethanol‐induced ataxia than the ISS controls. Additionally, the hypothermic response seems affected by Lore4 and Lore5 and maybe others.Conclusions At least two regions carrying a QTL specifying sensitivity to high doses of ethanol cospecify altered sensitivity in other measures of alcohol action. Specifically, these QTLs clearly affect ethanol‐induced hypothermia and pentobarbital‐induced LORR and possibly ethanol‐induced ataxia.
A Three‐Stage Alcohol Clamp Procedure in Human Subjects
Authors: Subramanian Marappa G. , Heil Sarah H. , Kruger Michael L. , Collins Karen L. , Buck Philip O. , Zawacki Tina , Abbey Antonia , Sokol Robert J. , Diamond Michael P. 
Published: April 2006

Background Multiple factors can influence blood alcohol levels (BALs) after oral ethanol intake. To minimize the variability in BALs, an alcohol “clamping” method in which alcohol is administered intravenously has been previously reported. We have modified this method and developed a multistage alcohol clamp procedure in humans.Methods Infusion of alcohol to achieve sequentially increasing steady‐state BALs at 50, 100, and 150 mg/dl (e.g., an alcohol clamp procedure) was performed in five subjects. The method used intravenous infusion of 6% alcohol in saline and followed a protocol generated by a physiologically based pharmacokinetic model for alcohol infusion. Real‐time measurement of BALs was used to base decisions for necessary adjustments in the infusion rates on a negative feedback principle to achieve and maintain the desired BALs. Additionally, in three of these subjects, breath alcohol levels were determined simultaneously with BAL measurements.Results A three‐stage alcohol clamp procedure was used to achieve BALs of 50, 100, and 150 mg/dl. The intra‐assay and interassay variations for measurement of BALs were 1.6 and 2.1%, respectively. The coefficients of variation for the 50, 100, and 150 mg/dl alcohol clamps were 9.8, 5.6, and 4.6%, respectively. The deviation from target BALs for the three clamps were less than 5%. Breath alcohol levels were lower than BALs across all time points, with the mean ratio between the two being 0.84. Correlation analysis showed a very strong correlation between the two alcohol measurement methods (r= 0.96;p < 0.001).Conclusions A three‐stage alcohol clamp procedure (50, 100, and 150 mg/dl) has been developed by following a protocol generated with a physiologically based pharmacokinetic model for alcohol infusion in human subjects. This is a suitable procedure to examine the responses on cognitive measures and physiologic parameters under steady states of desired BALs.