bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chlormethiazole Treatment Prevents Reduced Hepatic Vitamin A Levels in Ethanol‐Fed Rats
Authors: Liu Chun , Chung Jayong , Seitz Helmut K. , Russell Robert M. , Wang Xiang‐Dong 
Published: April 2006

Background Chronic ethanol intake results in decreased hepatic vitamin A levels through both enhanced degradation of vitamin A via a cytochrome P450 enzyme (CYP)‐dependent process and increased mobilization of vitamin A from the liver into the circulation. This study investigated whether treatment with chlormethiazole, a CYP inhibitor, restores vitamin A in the livers of ethanol‐fed rats.Methods Ethanol‐exposed and non‐ethanol‐exposed rats were treated with or without chlormethiazole (10 and 100 mg/kg body weight) for 1 month. Liver and plasma levels of retinol and retinyl palmitate were analyzed by high‐performance liquid chromatography. Expressions of hepatic lecithin:retinol acyltransferase (LRAT) and cellular retinol‐binding protein were analyzed with reverse transcription‐polymerase chain reaction. Hepatic retinol esterification by LRAT was examined by using incubations of the microsomal fractions of livers with exogenous sources of retinol.Results Ethanol‐feeding in rats for a month resulted in lower hepatic levels of retinol and retinyl palmitate than those found in controls and the occurrence of several polar retinoid metabolites. In contrast, treatment with chlormethiazole at two different doses in ethanol‐fed rats completely blocked the formation of hepatic retinoid polar metabolites and restored hepatic levels of retinol and hepatic retinyl palmitate in a dose‐dependent manner. Furthermore, increased plasma concentrations of retinyl palmitate in rats fed with ethanol, which indicate increased mobilization of vitamin A, were partially inhibited by chlormethiazole treatment. However, neither ethanol nor chlormethiazole treatment altered the expression and activity of LRAT in the liver of rats. Hepatic expression of cellular retinol‐binding protein increased significantly in ethanol‐fed rats with or without chlormethiazole treatment compared with control rats.Conclusions These data suggest that chlormethiazole can restore both hepatic retinol and retinyl ester concentrations to normal levels in ethanol‐fed rats through blocking enhanced both degradation of vitamin A and mobilization of vitamin A from the liver into the circulation.
Ethanol Induces Redox‐Sensitive Cell‐Cycle Inhibitors and Inhibits Liver Regeneration After Partial Hepatectomy
Authors: Koteish Ayman , Yang Shiqi , Lin Huizhi , Huang Jiawen , Diehl Anna Mae 
Published: April 2006

Background Doses of ethanol (EtOH) that are not overtly cytotoxic inhibit mitogen‐induced hepatocyte proliferation and delay liver regeneration after 70% partial hepatectomy (PH). The mechanisms for this are poorly understood. This study evaluates the hypothesis that EtOH inhibits hepatocyte proliferation after PH by inducing redox‐sensitive factors, such as p38 mitogen‐activated protein kinase (MAPK) and p21 (WAF1/CIP1), that protect cells from oxidative stress but prevent cell‐cycle progression by inhibiting cyclin D1.Methods Mechanisms that regulate the transition from the prereplicative G1 phase of the cell cycle into S phase were compared in EtOH‐fed mice and normal pair‐fed mice after PH.Results Prior EtOH exposure significantly increases p38 MAPK and p21 after PH. This is accompanied by reduced expression of cyclin D1 messenger RNA and protein, increases in other cell‐cycle regulators (such as signal transducer and activator of transcription‐3 and p27) that are normally inhibited by cyclin D1, and hepatocyte G1 arrest.Conclusions EtOH amplifies G1 checkpoint mechanisms that are induced by oxidative stress and promotes hepatic accumulation of factors, including p38 MAPK, p21, and signal transducer and activator of transcription‐3, that enhance cellular survival after oxidant exposure. Therefore, cell‐cycle inhibition may be an adaptive response that helps EtOH‐exposed livers survive situations, such as PH, that acutely increase reactive oxygen species in hepatocytes.
Quantitative Immunocytochemistry of GABA and Synaptophysin in the Cerebellar Cortex of Old Ethanol‐Fed Rats
Authors: Dlugos Cynthia A. , Pentney Roberta J. 
Published: April 2006

Background Ethanol‐related synaptic loss, Purkinje neuron dendritic regression, and parallel fiber degeneration have been reported in the molecular layer of the adult cerebellar cortex. The known plasticity of the cerebellar cortex suggests that this region may respond to ethanol‐related losses by compensatory remodeling of cerebellar circuitry. Stellate and basket interneurons may play an essential role in the remodeling process. Little is known about ethanol‐related effects on cerebellar interneurons or on the GABAergic synapses that they form despite the fact that ethanol‐related alterations in these components may contribute to the sensitivity of the cerebellum to ethanol. The paucity of data on GABAergic synapses extends to other synaptic components as well including synaptophysin, a glycoprotein component of synaptic vesicles and a synaptic marker.Methods Thirty 12‐month‐old F 344 rats were divided into ethanol‐fed, pair‐fed, and chow‐fed groups (10/group). Ethanol rats were treated for 40 weeks with a liquid diet in which 35% of the calories were derived from ethanol. At the end of treatment, rats were perfused, and tissue processed for quantitative immunohistochemistry of GABA and synaptophysin labels.Results Levels of GABA within inhibitory synapses formed by stellate and basket neurons and levels of synaptophysin were not altered by long‐term ethanol treatment.Conclusions Stable levels of GABA within GABAergic basket and stellate interneuron synapses suggest that interneurons in the molecular layer of the cerebellar cortex may not play a major role in remodeling of cerebellar circuitry following long‐term ethanol consumption. The lack of ethanol‐related alterations in synaptophysin levels reported here suggests that synaptic vesicles may be relatively insensitive to ethanol and that known ethanol‐related effects on synapse number are due to other mechanisms.
Influence of Ethanol Consumption on Experimental Viral Hepatitis
Authors: Jerrells Thomas R. , Mitchell Kristen , Pavlik Jacqueline , Jerrells Jennifer , Hoerman Debbie 
Published: April 2006

Background One important contributor to pathologic effects on the liver associated with alcohol abuse is viral hepatitis, especially hepatitis C virus (HCV) infection. Alcohol consumption has been shown to be associated with more severe HCV infection and hepatitis. The mechanisms of the more severe viral infection of the liver are unclear, and studies have been hampered by the lack of an animal model of hepatotropic viral infections.Methods We have established a murine model system of viral hepatitis in which C57BL/6 mice are infected with murine cytomegalovirus, a herpesvirus that produces self‐limiting hepatitis in immunocompetent mice. Mice were fed a liquid diet containing 36% ethanol‐derived calories with a pair‐feeding protocol. After infection with a sublethal dose of murine cytomegalovirus, the severity of liver infection was determined by measuring serum levels of alanine aminotransferase and by histological evaluation. Other parameters determined included the serum levels of cytokines, cytokine RNA in liver samples, and viral concentration in liver samples.Results Ethanol‐fed mice showed more severe hepatitis in the later stages of the infection as compared with the hepatitis noted in control mice. The ethanol‐fed mice did not control the virus replication in the liver, which was associated with a greater mononuclear cell inflammatory response, composed predominantly of cells with morphological characteristics of lymphocytes and macrophages. The early production of interferon γ, as well as production throughout the infection, was significantly lower in the ethanol‐fed mice. The early production of interleukin 12 was also less in ethanol‐fed mice.Conclusions The more severe hepatitis seen in the ethanol‐fed mice is likely to be the result of an inability to control the growth of the virus, which is associated with a continued inflammatory response. The inability to control the virus in the liver may be related to the decreased production of interferon γ and interleukin 12.
Dose‐Dependent Effects of Prenatal Ethanol Exposure on Synaptic Plasticity and Learning in Mature Offspring
Authors: Savage Daniel D. , Becher Matthew , de la Torre Alejandro J. , Sutherland Robert J. 
Published: April 2006

Background We have observed profound deficits in hippocampal synaptic plasticity and one‐trial learning in offspring whose mothers drank moderate quantities of ethanol during pregnancy. In the present study, we examined the question of whether lower maternal blood ethanol concentrations (BECs) could produce functional deficits in offspring.Methods Rat dams consumed either a 2%, 3%, or 5% ethanol liquid diet throughout gestation. Three other groups of dams were pair‐fed a 0% ethanol liquid diet, and a seventh group consumed lab chow ad libitum. Adult offspring from each diet group were assigned either to studies of evoked [3H]‐D‐aspartate (D‐ASP) release from hippocampal slices or spatial learning studies using the Morris Water Task.Results Consumption of the 2%, 3%, and 5% ethanol liquid diets produced mean peak maternal BECs of 7, 30 and 83 mg/dL, respectively. Consumption of these ethanol diets had no effect on offspring birthweight, litter size or neonatal mortality. Likewise, evoked D‐ASP release from hippocampal slices and performance on a standard version of the Morris Water Task were not affected by prenatal ethanol exposure. By contrast, activity‐dependent potentiation of evoked D‐ASP release from slices and one‐trial learning on a “moving platform” version of the Morris Water Task were markedly reduced in offspring whose mothers consumed the 5% ethanol liquid diet. Intermediate deficits in these two parameters were observed in offspring from the 3% ethanol diet group, whereas offspring from the 2% ethanol diet group were not statistically different than controls.Conclusions We conclude that the threshold for eliciting subtle, yet significant learning deficits in offspring prenatally exposed to ethanol is less than 30 mg/dL. This BEC is roughly equivalent to drinking 1 to 1.5 ounces of ethanol per day.
Acamprosate Inhibits the Binding and Neurotoxic Effects of Trans‐ACPD, Suggesting a Novel Site of Action at Metabotropic Glutamate Receptors
Authors: Harris Barton R. , Prendergast Mark A. , Gibson D. Alex , Rogers D. Trent , Blanchard John A. , Holley Robert C. , Fu May C. , Hart Stewart R. , Pedigo Norman W. , Littleton John M. 
Published: April 2006

Background Several reported effects of acamprosate within the glutamatergic system could result from interactions with metabotropic glutamate receptors (mGluRs). The following experiments were performed to determine whether acamprosate could compete with trans‐ACPD (±‐1‐aminocyclopentane‐trans‐1,3‐dicarboxylic acid, an equimolecular mixture of 1 S, 3 R and 1 R, 3 S‐ACPD and an agonist at both group I and group II mGluRs) sensitive binding sites and protect against trans‐ACPD–induced neurotoxicity in organotypic hippocampal slice cultures.Methods A P2 membrane preparation of cortices, cerebellums, and hippocampi of adult, male Sprague Dawley rats was used to determine the abilities of N‐methyl‐d‐aspartic acid (NMDA) and trans‐ACPD to displace [3H]glutamate in both the absence and the presence of the sodium salt of acamprosate (sodium mono N‐acetyl homotaurine or Na‐acamprosate). A comparison of the effects of 100 μM guanosine 5′‐triphosphate on unlabeled glutamate, trans‐ACPD, and Na‐acamprosate was performed in the same paradigm. For the neurotoxicity studies, organotypic hippocampal slice cultures from male and female 8‐day‐old neonatal rats were exposed to either 500 μM trans‐ACPD or 50 μM NMDA for 24 hr in normal culture medium containing serum on day 20 in vitro. The effects of Na‐acamprosate and 2‐methyl‐6‐(2‐phenylethenyl)pyridine (SIB‐1893), a noncompetitive antagonist at metabotropic type 5 receptors (mGluR5s), were assessed by determining differences in propidium iodide uptake as compared with neurotoxic challenges alone.Results Na‐acamprosate displaced 31% of [3H]glutamate but did not compete with NMDA for [3H]glutamate binding sites. Na‐acamprosate displayed total competition with trans‐ACPD. The presence of 100 μM guanosine 5′‐triphosphate differentially altered the displacing capabilities of the two mGluR agonists, unlabeled glutamate and trans‐ACPD, as compared with Na‐acamprosate. Na‐acamprosate (200–1000 μM) and SIB‐1893 (20–500 μM) both were neuroprotective against trans‐ACPD induced neurotoxicity that likely results from mGluR potentiation of NMDARs. In turn, Na‐acamprosate and SIB‐1893 had no direct effects on NMDA‐induced neurotoxicity.Conclusions Na‐acamprosate demonstrates the binding and functional characteristics that are consistent with a group I mGluR antagonist. The functional similarities between Na‐acamprosate and SIB‐1893 support an interaction of Na‐acamprosate at mGluR5s. The neuroprotective properties of acamprosate and possibly its ability to reduce craving in alcohol‐dependent patients may result from its alterations in glutamatergic transmission through mGluRs.
Differential Effects of Alcohol Consumption on Eukaryotic Elongation Factors in Heart, Skeletal Muscle, and Liver
Authors: Vary Thomas C. , Nairn Angus C. , Deiter Gina , Lang Charles H. 
Published: April 2006

Background Acute and chronic alcohol administration diminishes rates of protein synthesis in a variety of tissues including skeletal muscle, heart, and liver, through a diminished translational efficiency rather than a reduction in the number of ribosomes.Methods The purpose of the present study was to examine the effect of chronic alcohol exposure (8, 12, or 16 weeks) on elongation factors (eEF) as a potential mechanism for controlling mRNA translation in psoas, soleus, heart, and liver. The cellular content of eEF1A and eEF2 and the phosphorylation state of eEF2 in each tissue was measured using immunoblot techniques.Results The protein content of eEF1A was reduced in psoas, heart, and liver (but not soleus) from rats fed a diet containing alcohol for 16 weeks, but not for 8 or 12 weeks, compared with time‐matched pair‐fed controls. eEF2 content was only reduced in myocardium after feeding rats an alcohol‐containing diet for 16 weeks. In other tissues, no change in eEF2 content was observed. The decreases in eEF protein content were not associated with a concomitant reduction in the mRNA abundance for eEF1A or eEF2. The phosphorylation state of eEF2 was not affected by chronic alcohol consumption in the skeletal muscle or heart. In contrast, the level of eEF2 phosphorylation in the liver was reduced after 8, 12, and 16 weeks of feeding rats an alcohol‐containing diet. In contrast, acute alcohol intoxication failed to modulate the content of eEF1A or eEF2 in any of the tissues examined. The phosphorylation state of eEF2 was reduced in psoas following acute alcohol intoxication.Conclusions A decreased eEF1A protein content could account, in part, for the inhibition of translational efficiency following chronic (16 weeks) alcohol feeding but not the response to acute alcohol intoxication.
Sodium Sensitivity as a Main Determinant of Blood Pressure Changes during Early Withdrawal in Heavy Alcoholics
Authors: Di Gennaro Cristiana , Vescovi Pier Paolo , Barilli Angela Luciana , Giuffredi Cristina , Delsignore Roberto , Montanari Alberto 
Published: April 2006

Background Stimulated sympathetic nervous system, renin‐angiotensin‐aldosterone system, vasopressin, and cortisol are thought to affect blood pressure in early withdrawal of alcoholics. Hyperactivity of sodium‐retaining systems with consequent volume expansion also could interact with sodium sensitivity as previously found in long‐term withdrawing alcoholics.Methods To investigate this hypothesis, blood pressure and sodium balance were measured during the first 8 days of withdrawal in 18 chronic alcoholics on a 150 mM Na diet. Results were related to the Salt Sensitivity Index of blood pressure as measured in the same alcoholics after 1 year of abstinence.Results Early withdrawal study: there was a positive sodium balance (+288.6 ± 45.6 mM;p < 0.0001) and rise in mean arterial pressure (+11.8 ± 2.9 mm Hg;p= 0.001) during early withdrawal on 150 mM Na diet. Salt Sensitivity Study after long‐term detoxification: the shift from low (55 mM) to high sodium (260 mM) intake produced a larger (p= 0.04) increase in mean arterial pressure in alcoholics (+9.3 ± 2.0 mm Hg) than in 30 teetotal controls (+5.1 ± 1.1) (Salt Sensitivity Index, 0.047 ± 0.008 vs. 0.023 ± 0.0053;p < 0.05). Changes in mean blood pressure during withdrawal were highly related to sodium sensitivity index (r= 0.8;p < 0.001).Conclusions Early withdrawing alcoholics exposed to a normal sodium intake experience positive Na balance and increase in blood pressure that is related to sodium sensitivity measured after long‐term detoxification. This suggests that salt sensitivity plays a key role in blood pressure regulation in early withdrawing alcoholics.
Alcohol is the Main Factor in Excess Traffic Accident Fatalities in France
Authors: Reynaud Michel , Le Breton Patrick , Gilot Bertrand , Vervialle Françoise , Falissard Bruno 
Published: April 2006

Background The aim of this study was to better evaluate the role of alcohol drinking in fatalities linked to road traffic accidents.Methods The data of accidents were collected by a French official agency from police records, including many variables, among which was a blood alcohol test. They were analyzed in a descriptive way and toward a logistic regression. This exhaustive database comprised all of the 500,961 accidents with casualties that involved less than three vehicles (28,506 fatal accidents) recorded in France during a 52 month period (September 1995 to December 1999). The results of the alcohol tests were known in 78.7 of the drivers.Results The blood alcohol concentration was over the legal limit (0.50 g/L in France) in 9.8% of the accidents with casualties overall. Considering only fatal accidents, the rate of positive alcohol test in drivers was approximately 31.5%. This rate varied depending on the period and the type of accident, raising up to 71.2% in single‐vehicle accidents (loss of control) at night during the weekend. The percentage of positive alcohol tests also dramatically increased following the number of fatalities per accident (87.5% in single‐vehicle accidents during weekend nights involving three or more killed). The logistic regression in single‐vehicle accident shows that the higher odds ratios concern the positive blood alcohol test (OR = 4.19), clearly overwhelming the other precipitating factors of accidents (age of driver, meteorological conditions, time of day, and other factors).Conclusions Drinking alcohol before driving is a well known factor of accidents. We clearly demonstrate here that it is the main factor leading to deaths linked to road traffic accidents in France. The results are strengthened, and some analyses are allowed, by the exceptional features of our database. The authors emphasize the need for prevention measures.
Interhemispheric Transfer in Children with Heavy Prenatal Alcohol Exposure
Authors: Roebuck Tresa M. , Mattson Sarah N. , Riley Edward P. 
Published: April 2006

Background Prenatal alcohol exposure has long been associated with alterations in brain structure and behavioral changes. The corpus callosum can be affected by heavy prenatal alcohol exposure, and agenesis (absence) of this structure occurs more often in children with fetal alcohol syndrome than in the general population or in other developmentally delayed populations. Although the majority of children with fetal alcohol syndrome do not have agenesis of the corpus callosum, callosal area is reduced in this population, particularly in the anterior and posterior regions. However, the functional implication of these size reductions has not been examined.Methods The current study used a finger localization task to measure the transfer of information across the corpus callosum in children and adolescents with histories of heavy prenatal alcohol exposure and age‐ and sex‐matched controls. In a subset of children, correlational analysis was also conducted between behavioral data and cross‐sectional area of the corpus callosum.Results When compared with nonexposed controls, alcohol‐exposed children made more errors on trials for which information had to cross the corpus callosum (“crossed” trials) than on trials for which it did not (“uncrossed” trials), and they also made more errors as the task increased in complexity. Additionally, correlations with magnetic resonance imaging data in a subset of children revealed that impairment in interhemispheric transfer was related to reductions in the size of the corpus callosum. These correlations were independent of effects expected from the relationship between corpus callosum size and general intellectual functioning alone.Conclusions These findings suggest that children with heavy prenatal alcohol exposure display subtle deficits in the interhemispheric transfer of information in the somatosensory domain. Such deficits in interhemispheric transfer are likely to be related to the myriad of other behavioral and cognitive impairments observed in these children.
Inhibition of NF‐κB Binding Correlates With Increased Nuclear Glucocorticoid Receptor Levels in Acute Alcohol‐Treated Human Monocytes
Authors: Mandrekar Pranoti , Bellerose Gary , Szabo Gyongyi 
Published: April 2006

Background Acute alcohol treatment blocks inflammatory cytokines via inhibition of NF‐κB in monocytes in the presence of ongoing IκBα degradation, suggesting regulation of NF‐κB activation downstream of IκBα degradation. DNA binding of NF‐κB has been suggested to be regulated by other nuclear regulatory factors, including the glucocorticoid receptor (GR). Here, we show for the first time that acute alcohol (25 mM) exposure modulates GR activation in monocytes.Methods Human peripheral blood monocytes were treated with lipopolysaccharide (LPS) in the presence or absence of alcohol (25 mM) for 1 hour. Nuclear GR levels were estimated by Western blotting and NFκB activation was studied in the same extracts by gel shift analysis (EMSA). Cells were stimulated with 1 μM of Dex to be used as positive control for GR activation. GR/GRE binding was also determined in nuclear extracts by EMSA. IκBα mRNA known to be induced by GR/GRE activation was studied in total RNA extracts by the SuperArray method (SuperArray Inc., Bethesda, MD).Results LPS is a potent inducer of GR nuclear translocation and GR binding to the glucocorticoid response element (GRE). Acute alcohol treatment both induced (p < 0.05) and augmented (p < 0.05) LPS‐stimulated GR nuclear levels. However, alcohol inhibits LPS‐induced (nonligand bound) GR/GRE binding activity in monocytes. This inhibition of GR transactivation by alcohol was further confirmed by decreased expression (40%) of a target gene, IκBα. Thus, alcohol treatment increases nonligand‐bound nuclear GR, but inhibits its transactivation function. Ligand‐induced GR/GRE binding was decreased in alcohol‐treated monocytes. Inhibition of ligand‐induced GR/GRE binding by alcohol exposure is likely due to cytoplasmic retention of the GR.Conclusions Our results show that acute alcohol exposure inhibits GR in monocytes by differently affecting ligand‐ and nonligand‐induced GR nuclear translocation. These data also suggest that acute alcohol regulates GR activation in monocytes concomitant to inhibition of NF‐κB activation.