bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of Moderate Drinking on Purine and Carbohydrate Metabolism
Authors: Nishioka Kusuki , Sumida Takayuki , Iwatani Masako , Kusumoto Aki , Ishikura Yoshiyuki , Hatanaka Haruyo , Yomo Hideko , Kohda Hirofumi , Ashikari Toshihiko , Shibano Yuji , Suwa Yoshihide 
Published: April 2006

Background We examined the influences of a moderate intake level of three types of alcoholic beverages—beer, whisky, and Shochu (Japanese distilled liquor)—on purine and carbohydrate metabolism and excretion in healthy male volunteers, concerning (1) the extent of contribution of purine bodies contained in beer to uric acid metabolism and (2) a comparison between two types of distilled spirits with (whisky) and without (Shochu) aging in oak wood barrel storage.Methods Three sets of studies were conducted in which 10 to 13 healthy adult men were instructed to drink three types of alcoholic beverages at a slightly higher level (0.8 ml of ethanol equivalent/kg body weight) than moderate drinking (approximately 30.4 ml or less for men). A low purine beer was test‐manufactured by treating nucleosides that were contained in wort and remained in beer with purine nucleoside phosphorylase derived from Ochrobacterium anthropi, thereby converting them into corresponding purine bases that were easily assimilated by beer yeast.Results Although beer intake enhanced the level of serum uric acid by 13.6%, blood glucose by 26.7%, and insulin level by 5.1‐fold, drinking a moderate level of distilled liquor (whisky, Shochu) did not increase the serum uric acid level or the other two parameters. The serum uric acid level observed after drinking beer with a purine body concentration reduced by 28% (68% in nucleosides and purine bases) was almost identical to the level observed after drinking regular beer. Whisky has been found to have a property that decreases the serum uric acid level. Excretion of uric acid from blood is increased by 27% after drinking whisky.Conclusions Moderate drinking of distilled liquors did not enhance serum uric acid level, blood glucose, or insulin level in healthy male subjects. Increased serum uric acid after beer intake could not be explained mostly with their purine body congeners. Whisky showed the eliminative property in serum uric acid through excretion of it from blood to urine. At a moderate drinking level, beer and whisky have different effects on purine metabolism or excretion.
Up‐regulation of Transferrin Receptor Expression in Hepatocytes by Habitual Alcohol Drinking Is Implicated in Hepatic Iron Overload in Alcoholic Liver Disease
Authors: Suzuki Yasuaki , Saito Hiroyuki , Suzuki Masako , Hosoki Yayoi , Sakurai Shinobu , Fujimoto Yoshinori , Kohgo Yutaka 
Published: April 2006

Background Hepatic iron overload is often seen in alcoholic liver disease (ALD). We previously reported that the expression of 4‐hydroxy‐2‐nonenal‐protein adducts, which is a lipid peroxidative product and can be used as a marker of radical‐mediated cellular damage, was increased in iron‐overloaded hepatocytes with ALD. However, the mechanism of hepatic iron overload in ALD has not been clarified. In this study, to elucidate the mechanism of hepatic iron overload in ALD, we immunohistochemically investigated the expression of transferrin receptor (TfR), which mainly acts for cellular iron uptake.Methods Hepatic tissues were obtained from 31 patients with ALD and 5 normal livers by percutaneous needle biopsy under laparoscopy or ultrasound guidance. Chemical detection of hepatic iron accumulation was performed by Perls’ Prussian blue stain. Immunohistochemical detection of TfR expression was done using human monoclonal anti‐TfR antibody (TR104) according to the avidin‐biotin complex method with alkaline phosphatase.Results Excess iron accumulation was found in 22 hepatic tissues with ALD but not in any normal hepatic tissues. TfR expression was increased in hepatocytes of 18 hepatic tissues with ALD but was not detected in any normal hepatic tissues. The mean duration of abstinence of patients who demonstrated positive TfR expression in hepatocytes was significantly shorter than that of patients who demonstrated negative TfR expression (positive: 14 days; negative: 30 days). However, total ethanol consumption, daily ethanol intake, and serum aspartate aminotransferase and γ‐glutamyl transpeptidase values on admission were not significantly correlated with TfR expression in hepatocytes.Conclusions The up‐regulation of TfR expression in hepatocytes is implicated in hepatic iron overload in ALD, and habitual alcohol drinking is an important factor for the induction of TfR expression.
Ethanol‐Induced Cas Tyrosine Phosphorylation and Fyn Kinase Activation in Rat Brain
Authors: Nishio Hajime , Suzuki Koichi 
Published: April 2006

Background Tyrosine phosphorylation signaling has been reported to be involved in regulatory mechanisms of ethanol‐induced modulation of the central nervous system.Methods We investigated the effect of ethanol administration on tyrosine phosphorylation signaling in rat brain and also examined the possible involvement of Fyn kinase in the process.Results Immunoprecipitation experiments showed that Crk‐associated src substrate (Cas) was tyrosine‐phosphorylated in response to ethanol administration. Fyn kinase was shown to be activated by ethanol administration and to phosphorylate Cas on tyrosine residue in vitro. Furthermore, Fyn kinase was co‐localized with Cas in rat cerebellum and cerebral cortex.Conclusions Cas was tyrosine‐phosphorylated in rat brain by ethanol administration, and Fyn kinase was most likely involved in the process.
Michaelis‐Menten Elimination Kinetics of Acetaldehyde During Ethanol Oxidation
Authors: Fujimiya Tatsuya , Yamaoka Kiyoshi , Ohbora Yumiko , Aki Toshihiko , Shinagawa Hiromi 
Published: April 2006

Background Acetaldehyde (AcH) is a toxic metabolite of ethanol (EtOH). The pharmacokinetics of blood AcH during EtOH oxidation was studied with or without the administration of aldehyde dehydrogenase 2 inhibitor (cyanamide) in rabbits.Methods An bolus of EtOH saline solution (0.25, 0.5, 1.0, 1.5, and 2.0 g/kg) was injected intravenously. Cyanamide was administered intraperitoneally (25 mg/kg body weight) to the cyanamide‐treated group. Blood EtOH and AcH concentrations were measured by using head‐space gas chromatography.Results In the control group, the first peak of the blood AcH appeared immediately and the second elevation appeared 1 to 4 hr after administration at a high EtOH dose. The blood AcH levels other than the second elevation part were significantly correlated to the blood EtOH levels. In the cyanamide‐treated group, a peak and a plateau formed at the time corresponding to the second peak in the control group. The peak and plateau concentration of AcH increased markedly. We attempted simultaneous curve fitting, using the five blood EtOH and AcH concentration‐time curves, to determine the pharmacokinetic model. Consequently, the AcH elimination was best described by a Michaelis‐Menten kinetic model in both groups.Conclusions The blood AcH profile was suggested to consist of the first and second components that are related to the blood EtOH concentration itself and the metabolic formation of AcH, respectively. With higher EtOH doses or aldehyde dehydrogenase 2 inhibition, the second component becomes prominent as a result of the capacity‐limited property of the metabolism of AcH, which is described by Michaelis‐Menten elimination kinetics.
Estriol Enhances Lipopolysaccharide‐Induced Increases in Nitric Oxide Production by Kupffer Cells via Mechanisms Dependent on Endotoxin
Authors: Enomoto Nobuyuki , Takei Yoshiyuki , Kitamura Tsuneo , Hirose Miyoko , Ikejima Kenichi , Sato Nobuhiro 
Published: April 2006

Background Estriol causes sensitization of Kupffer cells to lipopolysaccharide (LPS) via mechanisms dependent on gut‐derived LPS. Accordingly, this study examines the effect of estriol treatment on nitric oxide (NO) production from Kupffer cells.Methods Rats were given estriol (20 mg/kg body weight) intraperitoneally, and Kupffer cells were isolated 24 hr later. Some rats were treated for 4 days with 150 mg/kg/day of polymyxin B and 450 mg/kg/day of neomycin to prevent growth of intestinal bacteria, the primary source of endotoxin in the gastrointestinal tract. After addition of LPS, NO production by Kupffer cell was detected using a fluorescence indicator, DAF‐2.Results Twenty‐four hours after estriol administration, LPS‐induced NO production by Kupffer cells was enhanced as compared with control Kupffer cells. Sterilization of the gut with antibiotics blocked this enhancement.Conclusions Estriol treatment in vivo enhances LPS‐induced NO production in Kupffer cells.
Long‐Term Ethanol Feeding Enhances Susceptibility of the Liver to Orally Administered Lipopolysaccharides in Rats
Authors: Tamai Hironao , Horie Yoshineri , Kato Shinzo , Yokoyama Hirokazu , Ishii Hiromasa 
Published: April 2006

Background Endotoxin has been implicated in the pathogenesis and progression of alcoholic liver disease. However, it is still unclear how long‐term ethanol feeding affects absorption of endotoxin from the intestine and susceptibility of the liver to gut‐derived endotoxin. The object of this study was to determine the effect of long‐term ethanol feeding on hepatic susceptibility to orally administered endotoxin.Methods Male Wistar rats that weighed approximately 150 g were pair‐fed with an ethanol‐containing liquid diet or a control diet for 35 days. In some experiments, 0, 10, or 20 mg/kg of lipopolysaccharides (LPS) was added to the liquid diet for 7 days beginning on day 29. On day 36, the animals were killed for blood biochemistry and histologic examination of the liver. We also determined plasma endotoxin levels after 20 mg/kg of LPS administration using a gastric tube. In another set of experiments, we determined intestinal permeability using FD4 (fluorescein isothiocyanate‐labeled dextran with an average molecular weight of 4000 D).Results With 10 mg/kg of LPS, serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels were significantly increased in the ethanol‐fed rats but not in controls. After 20 mg/kg of LPS administration, more substantial increases in serum ALT and ALP levels were observed in ethanol‐fed rats as compared with control diet‐fed rats. Plasma endotoxin levels in long‐term ethanol‐fed rats were higher than those in control rats after intragastric administration of high‐dose endotoxin (20 mg/kg). Furthermore, intestinal permeability to FD4 was increased by long‐term ethanol administration.Conclusions Long‐term ethanol feeding increases intestinal permeability to and absorption of endotoxin, which can sequentially enhance hepatic susceptibility to orally administered endotoxin. This model has potential as a subclinical experimental model for the study of alcoholic liver disease.
Are Relations Between Parental History of Alcohol Problems and Changes in Drinking Moderated by Positive Expectancies?
Authors: VanVoorst Wendy A. , Quirk Stuart W. 
Published: April 2006

Background: Risk factors of alcohol abuse generally have been examined for their additive or direct effects on the development of alcohol‐related problems. This study was designed to assess the interaction between two important predictors: parental history of alcohol problems and positive expectancies regarding alcohol consumption.Methods: The positive expectancies, reported parental alcohol problems, and alcohol use and problems of 169 first‐year college students were assessed at their entrance to college, and their alcohol use and problems were assessed again approximately 3 months later. The main effects of positive family history and expectancies as well as their interaction in predicting changes in alcohol use and problems were examined in hierarchical regression analyses.Results: A parental history of alcohol‐related problems was related to greater alcohol problems at the two assessment times, and positive expectancies for the effects of alcohol were related to both alcohol problems and alcohol use. The parental history × positive expectancies term significantly added to the prediction of changes in alcohol problems (8% incremental increase in explained variance) even after baseline problems were entered in a prior step in the equation. Follow‐up exploration revealed that the interaction was accounted for by high levels of alcohol problems at time 2 being reported by those high in positive expectancies and reporting high parental alcohol problems. The parental history × positive expectancies interaction term also added slightly to the prediction of changes in alcohol use amounts but accounted for a modest 1% incremental variance.Conclusions: Reported parental history and positive alcohol expectancies interacted to predict increases in alcohol problems over the course of the first semester of college. These results suggest that risk factors for alcohol problems may conjointly interact to confer heightened risk. Such interactive models may further assist in identifying at risk young adults. Limitations such as the reliance on self‐report measures and the predominantly female sample are discussed.
Financial Costs of Alcoholism Treatment Programs: A Longitudinal and Comparative Evaluation Among Four Specialized Centers
Authors: Nalpas B. , Combescure C. , Pierre B. , Ledent T. , Gillet C. , Playoust D. , Danel T. , Bozonnat M. C. , Martin S. , Balmès J. L. , Daurès J. P. 
Published: April 2006

Background: Alcoholism is a worldwide problem. Many strategies for alcohol detoxification and relapse prevention exist, but each alcohol treatment center has its own program. The objective of this study was to analyze and compare the financial cost and effectiveness of alcohol treatment programs from inpatient stay to follow‐up 1 year later. This was a prospective, open, nonrandomized study of 4 specialized alcohol treatment centers and 267 patients admitted for alcohol detoxification.Methods: We recorded all medical and nonmedical interventions related to the program during patient stay in the hospital and every 3 months after discharge for 1 year and recorded the occurrence of alcohol relapse. Financial evaluation was based on the prices of refund from the French national health insurance service.Results: The mean cost of hospitalization ranged from €1326 to €1917 (p= 0.001), a variation mainly due to the difference in the length of hospital stay but also to the cost of the inpatient program, routine medical checkups, and drugs administered. The mean cost of 1 year of follow‐up per patient ranged from €419 to €1704 (p= 0.001). The efficiency, corresponding to the money spent to prevent the relapse of one patient during 1 month, was approximately €500/month in three centers and €658 in the fourth. However, for a similar efficiency, the effectiveness, assessed by the mean time without relapse, was significantly (p= 0.001) different; center 1, which had the highest total cost, had an effectiveness 1.56 times higher than center 3, which had the lowest cost.Conclusions: This work emphasizes the heterogeneity of the costs and effectiveness of alcoholism treatment programs and suggests that research should be conducted to determine which program is the most rational, cost‐efficient, and beneficial for patients and the public health office economy.
Effect of Type of Alcoholic Beverages on Carbohydrate‐Deficient Transferrin, Sialic Acid, and Liver Enzymes
Authors: Sillanaukee P. , van der Gaag M. S. , Sierksma A. , Hendriks H. F. J. , Strid N. , Pönniö M. , Nikkari S. T. 
Published: April 2006

Background: There are only limited data obtained under well controlled conditions on the effects of moderate drinking on markers of alcohol use disorders. The aim of this study was to investigate the effects of moderate intake of different alcoholic beverages on these markers, including carbohydrate‐deficient transferrin (CDT), sialic acid (SA), and the liver enzymes γ‐glutamyltransferase, aspartate aminotransferase, and alanine aminotransferase.Methods: Eleven apparently healthy, nonsmoking middle‐aged men were included in a 12‐week randomized, diet‐controlled crossover trial according to a 4 × 4 Latin‐square design. Changes in CDT, SA, γ‐glutamyltransferase, aspartate aminotransferase, and alanine aminotransferase were analyzed after 3 weeks of daily intake of four glasses (40 g of alcohol) of red wine, beer, spirits (Dutch gin), or water (control).Results: After 3 weeks’ daily consumption of red wine, a significant decrease of serum CDT concentration was observed compared with water consumption. There was no effect of any alcoholic beverage on the other outcome measures.Conclusions: Daily consumption of 40 g of alcohol from different types of alcoholic beverages with dinner did not affect SA or liver enzymes. Further investigations to explore the mechanisms for the red wine–induced decreases of CDT, including changes in iron metabolism, are clearly needed.
Validity of Brief Alcohol Screening Tests Among Adolescents: A Comparison of the AUDIT, POSIT, CAGE, and CRAFFT
Authors: Knight John R. , Sherritt Lon , Harris Sion Kim , Gates Elizabeth C. , Chang Grace 
Published: April 2006

Background: Adolescents should be screened for alcohol misuse as part of routine care. The objective of this study was to compare the criterion validity of the Alcohol Use Disorders Identification Test (AUDIT), the Problem Oriented Screening Instrument for Teenagers substance use/abuse scale (POSIT), and the CAGE and CRAFFT questions among adolescents.Methods: Fourteen‐ to 18‐year‐old patients arriving for routine healthcare at a large, hospital‐based adolescent clinic completed the four screens and the criterion standard Adolescent Diagnostic Interview, which yields DSM‐IV diagnoses of alcohol abuse and dependence. Receiver operating characteristic (ROC) curves were plotted to determine optimal cut‐points. Areas under the ROC curves of the four screens were compared, and sensitivities and specificities were calculated.Results: Participants’ past 12‐month alcohol diagnostic classifications were as follows: no use (58.6%), nonproblem use (13.0%), problem use (20.8%), abuse (5.4%), and dependence (2.2%). Optimal cut‐points associated with problem use or higher were 2 for AUDIT, 1 for POSIT, 1 for CAGE, and 1 for CRAFFT. ROC curve area of the CAGE was significantly lower compared with areas of all other screens. Sensitivities (95% confidence intervals) were AUDIT 0.88 (0.83–0.93), POSIT 0.84 (0.79–0.90), CAGE 0.37 (0.29–0.44), and CRAFFT 0.92 (0.88‐0.96); specificities were AUDIT 0.81 (0.77–0.85), POSIT 0.89 (0.86–0.92), CAGE 0.96 (0.94–0.98), and CRAFFT 0.64 (0.59–0.69).Conclusions: The AUDIT, POSIT, and CRAFFT have acceptable sensitivity for identifying alcohol problems or disorders in this age group. The CAGE is not recommended for use among adolescents.
Inhibition of Alcohol‐Associated Colonic Hyperregeneration by α‐Tocopherol in the Rat
Authors: Vincon P. , Wunderer J. , Simanowski U. A. , Koll M. , Preedy V. R. , Peters T. J. , Werner J. , Waldherr R. , Seitz H. K. 
Published: April 2006

Background: Chronic alcohol consumption results in colorectal mucosal hyperregeneration, a condition associated with an increased risk for colorectal cancer. Possible mechanisms may involve the effects of acetaldehyde and/or free radicals generated during alcohol metabolism. Vitamin E is part of the antioxidative defense system, and its concentration is decreased or its metabolic utilization increased in various tissues after chronic alcohol consumption. We wondered whether α‐tocopherol supplementation may prevent ethanol‐induced colorectal cell cycle behavior and whether these changes were related to alterations in protein synthesis.Methods: Five groups of male Wistar rats, each consisting of 14 animals, received liquid diets as follows: group 1, alcohol; group 2, alcohol +α‐tocopherol; group 3, control (i.e., isocaloric glucose); group 4; control (i.e., isocaloric glucose) +α‐tocopherol. Group 5 was fed a solid chow diet ad libitum. After 4 weeks of feeding, immunohistology was performed with anti‐proliferating cell nuclear antigen (PCNA) or anti‐BCL2 antibodies. Fractional (ks) and absolute (Vs) rates of protein synthesis and rates of protein synthesis relative to RNA (kRNA) and DNA (kDNA) were measured with a flooding dose of L‐[4‐3H] phenylalanine with complementary analysis of protein and nucleic acid composition.Results: The PCNA index was increased significantly in the colon after ethanol administration compared with controls (ethanol, 10.3 ± 2.3 vs. control, 6.51 ± 1.6% PCNA positive cells, p < 0.05), although neither the protein, RNA, and DNA concentrations nor ks, kRNA, kDNA, and Vs were affected. This increase in PCNA index was significantly diminished by coadministration of α‐tocopherol (ethanol +α‐ tocopherol, 7.86 ± 1.71% PCNA positive cells, p < 0.05) without significant alterations in protein synthetic parameters. A similar result was obtained for the PCNA index in the rectal mucosa (ethanol, 14.6 ± 4.4 vs. control, 12.1 ± 4.2% PCNA positive cell), although this did not reach statistical significance. Neither ethanol nor α‐ tocopherol feeding had any significant effect on BCL‐2 expression in the colorectal mucosa. As with the colon, protein synthetic parameters in the mucosa were not affected by alcohol feeding at 4 weeks. These effects on colonic cell turnover without corresponding changes in protein synthesis thus represent a specific localized phenomenon rather than a general increase in anabolic processes in the tissue and reaffirm the hyperregenerative properties of chronic alcohol consumption.Conclusions: Alcohol‐associated hyperproliferation could be prevented, at least in part, by supplementation with α‐tocopherol. This may support the hypothesis that free radicals are involved in the pathogenesis of alcohol‐associated colorectal hyperproliferation.
Zinc Supplementation at the Time of Ethanol Exposure Ameliorates Teratogenicity in Mice
Authors: Carey Luke C. , Coyle Peter , Philcox Jeffrey C. , Rofe Allan M. 
Published: April 2006

Background: We have previously demonstrated that ethanol teratogenicity in mice is related to the maternal expression of metallothionein (MT), a zinc (Zn)‐binding protein. Ethanol induces maternal liver MT, which causes plasma Zn concentrations to decrease as Zn moves into the liver. During pregnancy it is suggested that this change decreases fetal Zn supply and contributes to abnormal development. Here we investigated whether maternal Zn supplementation at the time of ethanol exposure reduces teratogenicity.Methods: Mice were injected with 25% ethanol (0.015 ml/g intraperitoneally at 0 and 4 hr) and ZnSO4 (2.5 μgZn/g subcutaneously at 0 hr) and were killed over 16 hr to ascertain changes in plasma Zn. Plasma Zn concentrations peaked at 2 hr, where levels were 5‐fold normal and then returned toward normal over 14 hr. Pregnant mice were treated in a similar manner on gestation day 8 with saline, saline + Zn, ethanol + Zn, or ethanol alone, and fetal abnormalities were assessed on gestation day 18.Results: External abnormalities were most prevalent in offspring from dams treated with ethanol. Zn treatment at the time of ethanol exposure reduced the incidence of fetal abnormalities to basal levels. Litters from dams treated with ethanol + Zn contained more fetuses and fewer fetal resorption sites compared with those from ethanol‐treated dams.Conclusions: These findings demonstrate that Zn supplementation at the time of ethanol exposure significantly negates the deleterious effects of ethanol on the fetus.