bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alcohol and Benzodiazepines in Fatal Poisonings
Authors: Koski Anna , Ojanperä Ilkka , Vuori Erkki 
Published: April 2006

Background Postmortem forensic toxicology frequently finds alcohol both alone and in combination with drugs. Although benzodiazepines are generally considered safe, they are considered dangerous with alcohol.Methods A retrospective statistical analysis of alcohol and benzodiazepine concentrations in postmortem blood samples included 808 cases diagnosed as fatal alcohol or drug intoxication involving (1) ethanol alone; (2) ethanol with temazepam; or (3) ethanol with any combination of diazepam, chlordiazepoxide, and nordazepam.Results The median concentration of ethanol was 3.3‰ in cases with ethanol alone and 3.5‰ when diazepam was present, but it was significantly lower, only 2.5‰, when temazepam was present in the blood. Furthermore, the median concentration of ethanol was 2.2‰ in cases with high concentrations (>0.9 mg/liter) of temazepam and 2.7‰ in cases with therapeutic (≤0.9 mg/liter) concentrations.Conclusions Diazepam and chlordiazepoxide pose a smaller risk of death by poisoning than does temazepam when given as a hypnotic to patients suffering from alcoholism.
Biological Markers of Alcohol Consumption in Nondrinkers, Drinkers, and Alcohol‐Dependent Brazilian Patients
Authors: Figlie N. B. , Benedito‐Silva A. A. , Monteiro M. G. , Souza‐Formigoni M. L. O. 
Published: April 2006

Background The purpose of this study was to compare the sensitivity and specificity of some new and traditional biological markers and indicators of health among Brazilian nondrinkers, drinkers, and alcohol‐dependent patients.Material and Methods We evaluated 130 nondrinkers, 167 drinkers, and 183 alcohol‐dependent drinkers from Brazil who participated in the WHO/ISBRA Study on State and Trait Markers of Alcohol Use and Dependence. A standardized WHO/ISBRA Interview Schedule provided background information on the subjects’ characteristics including reported health problems and alcohol consumption. Blood samples were analyzed for aspartate aminotransferase (AST), carbohydrate deficient transferrin (CDT), γ‐glutamyltransferase (GGT), blood alcohol levels (BAL), and platelet adenylate cyclase activity (basal levels [AC] and levels after stimulation with Gpp(NH)p, cesium fluoride, and forskolin).Results The alcohol‐dependent drinkers presented higher levels of AST, GGT, AC, CDT, and BAL than the nondrinkers and drinkers, whose levels were similar. Sex differences in the sensitivity of CDT and AC were found. The alcohol‐dependent women presented a lower prevalence of abnormal values of CDT and Gpp(NH)p‐stimulated AC than the alcohol‐dependent men, despite the fact that they presented similar alcohol consumption levels. The alcohol‐dependent drinkers presented a higher prevalence of clinical disorders than the nondrinkers and drinkers. The drinkers and alcohol‐dependent patients presented significantly higher rates of gastritis than the nondrinkers.Conclusions Sex differences in the sensitivity of CDT and AC suggest that these markers are not as sensitive at detecting excessive alcohol use in women as they are in men. If data from this Brazilian sample are compared with those reported for international samples, relevant differences are detected, which suggests that genetic and cultural differences should be considered in the selection of biological markers of heavy alcohol consumption.
The Ethanol Conjugate Ethyl Glucuronide Is a Useful Marker of Recent Alcohol Consumption
Authors: Martin Wurst Friedrich , Metzger Joerg 
Published: April 2006

Background Current biological state markers remain suboptimal with regard to sensitivity and specificity for monitoring alcohol consumption. The currently used state markers can be influenced by age, sex, and a variety of substances and non‐alcohol‐associated diseases and do not fully cover the time axis for alcohol intake. Ethyl glucuronide (EtG) is a promising, nonvolatile, water‐soluble marker of recent alcohol consumption that is stable during storage and can be detected for an extended time period (up to 80 hr) after alcohol is completely eliminated from the body.Patients and Methods In the WHO/ISBRA Study of State and Trait Markers of Alcohol Use and Dependence, EtG was determined in urine samples from 304 patients with an liquid chromotography, electrospray ionization double mass spectrometry (ESI‐LC/MS‐MS) method. Deuterium labeled EtG was used as internal standard. Determination limit was 0.1 mg/liter. All measurements were performed in duplicate. A calibration solution was measured after each 10 samples.Results The following significant correlations were found for the Spearman rank correlation for the total sample between EtG and other variables: sobriety in days (r=−0.6), 5‐hydroxytryptophol to 5‐hydroxyindole‐3‐acetic acid (HTOL/HIAA) ratio (r= 0.58), ethanol level (r= 0.433), methanol level (r= 0.198), carbohydrate‐deficient transferrin (r= 0.458), γ‐glutamyltransferase (r= 0.428), aspartate aminotransferase (r= 0.260), age (r= 0.264), and total grams of ethanol consumed in the previous month (r= 0.467). In a subsample of 277 subjects in whom no ethanol was detectable in urine, the following correlations with EtG levels were found: sobriety (days;r=−0.597), HTOL/HIAA ratio (r= 0.478), γ‐glutamyltransferase (r= 0.422), total grams of ethanol consumed last month (r= 0.395), and carbohydrate‐deficient transferrin (r= 0.366; all significant at p < 0.05). When we compared results between EtG levels and the HTOL/HIAA ratio, 68.8% (n= 119) of those positive for EtG did not have elevated values for the HTOL/HIAA ratio. Thirty‐one percent (31.2%) of these 119 subjects were positive for both parameters, but of those negative for EtG, only 4.4% had an elevated HTOL/HIAA ratio.Conclusions EtG is a good candidate for a sensitive, specific, and reliable marker of recent alcohol intake. The complementary use of this marker with other biological state markers should significantly improve treatment outcome and therapy effectiveness and reduce costs.
Alcohol‐Induced Up‐Regulation of Fibrinolytic Activity and Plasminogen Activators in Human Monocytes
Authors: Tabengwa Edlue M. , Wheeler Crystal G. , Yancey Dwana A. , Grenett Hernan E. , Booyse Francois M. 
Published: April 2006

Background Moderate alcohol consumption is associated with reduced risk for coronary heart disease. This may due, in part to increased fibrinolysis. Monocytes synthesize fibrinolytic proteins, tissue plasminogen activator (t‐PA), urokinase plasminogen activator (u‐PA), and their receptors. These studies were carried out to determine the effect of low alcohol on monocyte fibrinolytic activity and PA messenger RNA (mRNA) synthesis.Methods Peripheral blood monocytes and U937 cells were incubated in absence/presence of low alcohol (0.1%, v/v) for various times (0–1 hr), followed by incubations in the absence of alcohol (0–24 hr) before measurement of fibrinolytic activity and PA mRNA levels (reverse transcriptase polymerase chain reaction).Results Brief exposure (15 min, 4°C) of U937 cells to low alcohol resulted in an approximately 2‐ to 3‐fold increase (269.0 ± 5.6 fmol/1 × 106 cells versus 656.0 ± 94.0 fmol/1 × 106 cells) in fibrinolytic activity. Preincubation of U937 cells and peripheral blood monocytes in low alcohol (1 hr, 37°C) followed by incubation in the absence of alcohol (24 hr) resulted in a sustained approximately 4‐ to 5‐fold increase (414.0 ± 174.7 vs. 965.33.0 ± 104.8 fmol/1 × 106 cells) and an approximately 3‐ to 4‐fold (20.5 ± 2.14 vs. 74 ± 2.28 fmol/2 × 106 cells, respectively) increase in fibrinolytic activity. Preincubation of monocytes with low alcohol (1 hr, 37°C) followed by incubation in the absence of alcohol (6 hr) resulted in an approximately 5‐ to 6‐fold (0.06 ± 0.02 vs. 0.42 ± 0.02) and an approximately 2‐ to 3‐fold (0.89 ± 0.04 vs. 2.07 ± 0.29) increase in t‐PA and u‐PA mRNA (reverse transcriptase polymerase chain reaction; PA/glyceraldehyde‐3‐phosphate dehydrogenase ratio), respectively.Conclusions These data suggest that low alcohol exerts a rapid, direct, and sustained effect on monocyte fibrinolytic activity, which may be, due in part, to increased monocyte t‐PA/u‐PA expression. These data provide a feasible molecular mechanism by which alcohol effects on monocyte fibrinolysis may contribute to the cardioprotective benefit associated with moderate alcohol consumption.
Myocardial Effects of Ethanol Consumption in the Rat With Streptozotocin‐Induced Diabetes
Authors: Giles Thomas D. , Given Michael B. , Greenberg Stan S. , Zhao Xinfang , Kerut Edmund Kenneth , McElwain Elizabeth , Allen Gayle 
Published: April 2006

Background Rats with streptozotocin (STZ)‐induced diabetes exhibit alterations in cardiac function, ventricular remodeling, and changes in cell signaling, which includes protein kinase C (PKC) isoforms. Moderate consumption of ethanol has a beneficial effect on cardiovascular outcomes in the general population, an effect that has recently been found to extend to patients with diabetes mellitus. We studied the effect of low‐dose ethanol consumption on cardiac function, geometry, and PKC isoforms in the rat with STZ‐induced diabetes.Methods Four groups of rats were studied over 8 to 10 weeks: control, STZ‐induced diabetes, 12% (v/v) ethanol consumption, and STZ‐induced diabetes plus 4% (v/v) ethanol consumption. Invasive hemodynamic measurements were performed; myocardial tissue was obtained for analysis for total PKC and cytosolic and membrane protein content of PKC‐α, PKC‐δ, and PKC‐ε, and two‐dimensional and M‐mode echocardiograms were obtained.Results Compared with rats with diabetes alone, consumption of 4% ethanol prevented the decrease in left ventricular dP/dt seen with diabetes alone, as well as the increase in left ventricular internal dimension. Up‐regulation of PKC‐α, ‐δ, and ‐ε occurring in the diabetic animals was also prevented by ethanol consumption, whereas ethanol alone had no effect on PKC isoform pattern.Conclusions These data suggest that STZ‐induced cardiac remodeling and dysfunction are associated with increases in PKC activity, particularly PKC‐α, ‐δ, and ‐ε, and that consumption of ethanol can prevent these changes.
Alcohol Consumption Is Associated With Enrichment of High‐Density Lipoprotein Particles in Polyunsaturated Lipids and Increased Cholesterol Esterification Rate
Authors: Perret Bertrand , Ruidavets Jean‐Bernard , Vieu Claude , Jaspard Béatrice , Cambou Jean‐Pierre , Terce François , Collet Xavier 
Published: April 2006

Background Alcohol consumption is associated with high levels of high‐density lipoproteins (HDLs). Moreover, changes in the fatty acid patterns of red blood cell phospholipids and plasma lipids have been observed in drinkers. The objectives of this study were to characterize the composition of HDL particles with respect to lipid molecular species in regular wine drinkers and to assess the functional properties of those HDLs as regards key steps of reverse cholesterol transport.Methods Forty‐six subjects were recruited in the frame of a population study performed in Toulouse, southern France, and a nutritional investigation, including daily alcohol consumption, was performed. Subjects were sorted according to their daily alcohol intake (0, ≤35, and >35 g/day), mostly as red wine. The plasma HDL fraction was isolated, and neutral lipid molecular lipids and phospholipid fatty acids were analyzed by gas liquid chromatography. Efflux of cellular cholesterol and rates of cholesterol esterification and cholesteryl ester transfers between lipoproteins were assayed in a cell‐plasma incubation system.Results Wine drinking, at 47 g/day, was associated with an increase in HDL cholesterol and apolipoprotein A‐I, but not with triglycerides. Isolated HDL displayed a 27% increase in all cholesteryl ester molecular species. The particles were also enriched in unsaturated phospholipids and, particularly, in those containing arachidonic (+30%) and eicosapentaenoic (+90%) acids. The plasma cholesterol esterification rate, reflecting lecithin cholesterol acyl transferase activity on HDL, was found to be higher (+27%) in drinkers than in nondrinkers, whereas the rate of cellular cholesterol efflux to plasma was identical.Conclusions Regular wine consumption is associated with high levels of polyunsaturated lipids in HDL and with increases in the cholesterol esterification rate.
The Relationship Between Hippocampal Acetylcholine Release and Cholinergic Convulsant Sensitivity in Withdrawal Seizure–Prone and Withdrawal Seizure–Resistant Selected Mouse Lines
Authors: Mark Gregory P. , Finn Deborah A. 
Published: April 2006

Background The septo‐hippocampal cholinergic pathway has been implicated in epileptogenesis, and genetic factors influence the response to cholinergic agents, but limited data are available on cholinergic involvement in alcohol withdrawal severity. Thus, the relationship between cholinergic activity and responsiveness and alcohol withdrawal was investigated in a genetic animal model of ethanol withdrawal severity.Methods Cholinergic convulsant sensitivity was examined in alcohol‐naïve Withdrawal Seizure—Prone (WSP) and—Resistant (WSR) mice. Animals were administered nicotine, carbachol, or neostigmine via timed tail vein infusion, and the latencies to onset of tremor and clonus were recorded and converted to threshold dose. We also used microdialysis to measure basal and potassium‐stimulated acetylcholine (ACh) release in the CA1 region of the hippocampus. Potassium was applied by reverse dialysis twice, separated by 75 min. Hippocampal ACh also was measured during testing for handling‐induced convulsions.Results Sensitivity to several convulsion endpoints induced by nicotine, carbachol, and neostigmine were significantly greater in WSR versus WSP mice. In microdialysis experiments, the lines did not differ in basal release of ACh, and 50 mM KCl increased ACh output in both lines of mice. However, the increase in release of ACh produced by the first application of KCl was 2‐fold higher in WSP versus WSR mice. When hippocampal ACh was measured during testing for handling‐induced convulsions, extracellular ACh was significantly elevated (192%) in WSP mice, but was nonsignificantly elevated (59%) in WSR mice.Conclusions These results suggest that differences in cholinergic activity and postsynaptic sensitivity to cholinergic convulsants may be associated with ethanol withdrawal severity and implicate cholinergic mechanisms in alcohol withdrawal. Specifically, WSP mice may have lower sensitivity to cholinergic convulsants compared with WSR because of postsynaptic receptor desensitization brought on by higher activity of cholinergic neurons.
Diurnal Effects of Acute and Chronic Administration of Ethanol on Sleep in Rats
Authors: Kubota Takeshi , De Alok , Brown Richard A. , Simasko Steven M. , Krueger James M. 
Published: April 2006

Background Disturbances in sleep patterns are a complicating factor in recovery from alcoholism. The effects of acute and chronic alcohol treatments on sleep in rats were determined.Methods Adult male Sprague‐Dawley rats were acclimated to a temperature‐controlled chamber, and electromyograms and electroencephalograms (EEGs) were obtained during 23‐hr recording sessions. Time spent in rapid eye movement sleep (REMS) and non‐REM sleep (NREMS), EEG slow‐wave activity (SWA) during NREMS, a spectral analysis of the EEG by fast Fourier transform, and brain temperatures were determined.Results Acute exposure to alcohol (2.3 and 3.0 g/kg) by gastric intubation at the beginning of dark onset produced an increase in NREMS and a suppression of SWA. Spectral analysis revealed that during the first 4 hr there was a small increase in very‐low‐frequency bands (0.5–2 Hz), with a suppression of higher‐frequency bands. This was followed by a suppression of low‐frequency bands. A dose of 3.0 g/kg at light onset caused an increase in NREMS and a suppression of SWA. Spectral analysis revealed a suppression of low‐frequency bands throughout the first 12 hr of recording but no change on high‐frequency bands with light‐onset alcohol. Chronic treatment with alcohol (6% alcohol in a liquid diet with pair‐fed isocaloric controls) for 3 weeks produced an increase in NREMS and a decrease in EEG power density in frequency bands above 2 Hz. Chronic alcohol also reduced the circadian variation of REMS, an effect that showed a rebound 1 week after the alcohol treatment was terminated. Two weeks after the alcohol treatment was stopped, NREMS and REMS values returned to baseline.Conclusions These results demonstrate differences in the effect of acute alcohol on sleep depending on the time of administration and demonstrate that distinct alterations in sleep patterns are induced by chronic treatments in as little as 3 weeks.
Nitrendipine Blocks the Nociceptive Effects of Chronically Administered Ethanol
Authors: Gatch Michael B. 
Published: April 2006

Background Calcium channel blockers prevent the development of tolerance to ethanol and prevent seizures and other signs of ethanol withdrawal. Calcium channels may also mediate the development of tolerance to the antinociceptive effects of ethanol.Methods A radiant‐heat tail‐flick assay was used to assess the effects of nitrendipine, a dihydropyridine L‐type calcium channel blocker, on ethanol‐induced changes in nociception in rats. Chronic effects of ethanol were tested in four groups of rats, which received 10 days of exposure to a liquid diet. The groups received twice‐daily injections of saline or nitrendipine (1, 5, or 10 mg/kg). Tail‐flick latencies were measured on days 0 (baseline), 2, 4, 6, 8, and 10 and at 12 hr after removal of the liquid diet.Results Chronic exposure to ethanol produced maximal levels of antinociception by day 4 of exposure. The observed level of antinociception gradually decreased to baseline levels by day 8. Marked decreases in tail‐flick latencies below baseline (hyperalgesia) were observed during ethanol withdrawal. Repeated administration of nitrendipine blocked the antinociceptive effects of chronic ethanol and prevented the hyperalgesia produced by ethanol withdrawal. The highest dose of nitrendipine (10 mg/kg, twice daily) reduced consumption of the ethanol diet.Conclusions L‐type calcium channel blockers block hyperalgesia during ethanol withdrawal and may mediate, at least in part, the antinociceptive effects of chronic ethanol.
Disruption of Maternal Behavior by Alcohol Intoxication in the Lactating Rat: A Behavioral and Metabolic Analysis
Authors: Pepino Marta Yanina , Abate Paula , Spear Norman E. , Molina Juan Carlos 
Published: April 2006

Background Preweanling rats exhibit clear behavioral signs of distress after interacting with an alcohol‐intoxicated dam. Interestingly, behavioral reactivity of infants to the experience of alcohol in the nursing context decreases as a function of repeated alcohol administrations to the mother. In this study, maternal activities were examined when dams were exposed to repeated administrations of a subnarcoleptic alcohol dose. Maternal changes in alcohol metabolism were also analyzed as a function of repeated exposures to the drug.Methods During postpartum days 3, 5, 7, 9, 11, and 13, nursing dams received an intragastric administration of either 2.5 g/kg of alcohol or water. Maternal behaviors were evaluated (experiment 1). Blood alcohol levels (BALs) of the dams were determined on postpartum day 16 after all mothers received either an intragastric (experiment 2) or an intraperitoneal (experiment 3) dose of alcohol. The doses used (2.5 g/kg intragastrically and 1.5 g/kg intraperitoneally) were chosen because they promote similar peak BALs in dams naive to alcohol.Results Maternal behaviors were strongly affected by the state of intoxication. Nevertheless, these disruptions clearly subsided with progression of alcohol‐related experiences (experiment 1). Chromatographic analysis of alcohol metabolism indicated the development of tolerance in dams that had prior experience with alcohol (experiment 2). Changes in BALs as a function of prior experience with alcohol seemed related to first‐pass alcohol metabolism rather than hepatic oxidative processes of the drug (experiments 2 and 3).Conclusions When the dam first experiences a moderate state of alcohol intoxication, maternal behaviors are uniformly disrupted. Subsequent exposures to alcohol lead to maternal metabolic tolerance. In conjunction with previous studies, these data indicate that infantile reactivity to alcohol is dependent on how the members of the dam/pup dyad express or perceive ethanol's postabsorptive effects.
Carbohydrate‐Deficient Transferrin and γ‐Glutamyltransferase for the Detection and Monitoring of Alcohol Use: Results From a Multisite Study
Authors: Anton Raymond F. , Lieber Charles , Tabakoff Boris 
Published: April 2006

Background The purpose of this article is to evaluate the biological marker of heavy alcohol use, carbohydrate‐deficient transferrin (CDT), in contrast to the older and more widely used γ‐glutamyltransferase (GGT) for the detection and monitoring of heavy alcohol use.Methods In this report, CDT and GGT sensitivity and specificity for heavy alcohol intake are examined in a large multisite study in which 444 recently admitted inpatient alcoholics were compared with 204 matched social drinker controls. In addition, changes in these biomarkers were evaluated during an initial abstinence period and biweekly over 14 weeks of monitoring to compare changes in CDT and GGT during continued abstinence or relapse.Results CDT and GGT were comparable in identifying heavy alcohol consumption in men, but GGT appeared to be better for women. For both genders, when these markers were combined, there was better sensitivity than when used alone. CDT and GGT both decreased during 4 weeks of abstinence. When we used a 30% increase from baseline abstinent levels as an indicator, CDT appeared marginally better than GGT at indicating relapse in men but not in women. For men in particular, relapse over the course of the study was best identified by evaluating changes (30% increase) in both markers simultaneously.Conclusions These results support the utility of CDT, especially when used in conjunction with GGT, as an aid in detecting and monitoring heavy alcohol consumption.