Characterization of sialic acid index of plasma apolipoprotein J and phosphatidylethanol during alcohol detoxification--a pilot study

Apolipoprotein J (ApoJ) is a component of plasma high-density lipoproteins. Previous studies have shown progressive recovery of ApoJ sialic acid content with increased duration of alcohol abstinence. Therefore, the sialic acid index of plasma apolipoprotein J (SIJ) seems to be a promising alcohol biomarker. Phosphatidylethanol (PEth) is a direct ethanol metabolite and has recently attracted attention as a biomarker of prolonged intake of higher amounts of alcohol. The aim of the pilot study was to explore sensitivity, specificity, and normalization of SIJ and PEth in comparison with traditional and emerging biomarkers.

Formation of Phosphatidylethanol and Its Subsequent Elimination During an Extensive Drinking Experiment Over 5 Days

BACKGROUND: For almost 30 years, phosphatidylethanol (PEth) has been known as a direct marker of alcohol consumption. This marker stands for consumption in high amounts and for a longer time period, but it has been also detected after 1 high single intake of ethanol (EtOH). The aim of this study was to obtain further information about the formation and elimination of PEth 16:0/18:1 by simulating extensive drinking. METHODS: After 3 weeks of alcohol abstinence, 11 test persons drank an amount of EtOH leading to an estimated blood ethanol concentration of 1 g/kg on each of 5 successive days. After the drinking episode, they stayed abstinent for 16 days with regular blood sampling. PEth 16:0/18:1 analysis was performed using liquid chromatography-tandem mass spectrometry (high-performance liquid chromatography 1100 system and QTrap 2000 triple quadrupole linear ion trap mass spectrometer. Values of blood alcohol were obtained using a standardized method with headspace gas chromatography flame ionization detector. RESULTS: Maximum measured concentrations of EtOH were 0.99 to 1.83 g/kg (mean 1.32 g/kg). These values were reached 1 to 3 hours after the start of drinking (mean 1.9 hours). For comparison, 10 of 11 volunteers had detectable PEth 16:0/18:1 values 1 hour after the start of drinking, ranging from 45 to 138 ng/ml PEth 16:0/18:1. Over the following days, concentrations of PEth 16:0/18:1 increased continuously and reached the maximum concentrations of 74 to 237 ng/ml between days 3 and 6. CONCLUSIONS: This drinking experiment led to measurable PEth concentrations. However, PEth 16:0/18:1 concentrations stayed rather low compared with those of alcohol abusers from previous studies.

Are there risk factors in alpine skiing? A controlled multicentre survey of 1278 skiers

OBJECTIVE: To analyse risk factors in alpine skiing. DESIGN: A controlled multicentre survey of injured and non-injured alpine skiers. SETTING: One tertiary and two secondary trauma centres in Bern, Switzerland. PATIENTS AND METHODS: All injured skiers admitted from November 2007 to April 2008 were analysed using a completed questionnaire incorporating 15 parameters. The same questionnaire was distributed to non-injured controls. Multiple logistic regression was performed. Patterns of combined risk factors were calculated by inference trees. A total of 782 patients and 496 controls were interviewed. RESULTS: Parameters that were significant for the patients were: high readiness for risk (p = 0.0365, OR 1.84, 95% CI 1.04 to 3.27); low readiness for speed (p = 0.0008, OR 0.29, 95% CI 0.14 to 0.60); no aggressive behaviour on slopes (p<0.0001, OR 0.19, 95% CI 0.09 to 0.37); new skiing equipment (p = 0.0228, OR 59, 95% CI 0.37 to 0.93); warm-up performed (p = 0.0015, OR 1.79, 95% CI 1.25 to 2.57); old snow compared with fresh snow (p = 0.0155, OR 0.31, 95% CI 0.12 to 0.80); old snow compared with artificial snow (p = 0.0037, OR 0.21, 95% CI 0.07 to 0.60); powder snow compared with slushy snow (p = 0.0035, OR 0.25, 95% CI 0.10 to 0.63); drug consumption (p = 0.0044, OR 5.92, 95% CI 1.74 to 20.11); and alcohol abstinence (p<0.0001, OR 0.14, 95% CI 0.05 to 0.34). Three groups at risk were detected: (1) warm-up 3-12 min, visual analogue scale (VAS)(speed) >4 and bad weather/visibility; (2) VAS(speed) 4-7, icy slopes and not wearing a helmet; (3) warm-up >12 min and new skiing equipment. CONCLUSIONS: Low speed, high readiness for risk, new skiing equipment, old and powder snow, and drug consumption are significant risk factors when skiing. Future work should aim to identify more precisely specific groups at risk and develop recommendations--for example, a snow weather index at valley stations.

Nimodipine prior to alcohol withdrawal prevents memory deficits during the abstinence phase

Effects of the dihydropyridine, nimodipine, an antagonist at L-type calcium channels, on the memory loss in rats caused by long term alcohol consumption were examined. Either a single dose of nimodipine or 2 weeks of repeated administration was given prior to withdrawal from 8 months of alcohol consumption. Memory was measured by the object recognition test and the T maze. Both nimodipine treatments prevented the memory deficits when these were measured between 1 and 2 months after alcohol withdrawal. At the end of the memory testing, 2 months after cessation of chronic alcohol consumption, glucocorticoid concentrations were increased in specific regions of rat brain without changes in plasma concentrations. Both nimodipine treatment schedules substantially reduced these rises in brain glucocorticoid. The data indicate that blockade of L-type calcium channels prior to alcohol withdrawal protects against the memory deficits caused by prolonged alcohol intake. This shows that specific drug treatments, such as nimodipine, given over the acute withdrawal phase, can prevented the neuronal changes responsible for subsequent adverse effects of long term consumption of alcohol. The results also suggest the possibility that regional brain glucocorticoid increases may be involved in the adverse effects of long term alcohol intake on memory. Such local changes in brain glucocorticoid levels would have major effects on neuronal function. The studies indicate that L-type calcium channels and brain glucocorticoid levels could form new targets for the treatment of cognitive deficits in alcoholics.

Depressive symptoms as a predictor of alcohol relapse after residential treatment programs for alcohol use disorder

Alcohol use disorder (AUD) and depressive disorders often co-occur. Findings on the effects of major depressive disorder (MDD) or depressive symptoms on posttreatment alcohol relapse are controversial. The study's aim is to examine the association of MDD and depressive symptoms with treatment outcomes after residential AUD programs. In a naturalistic-prospective, multisite study with 12 residential AUD treatment programs in the German-speaking part of Switzerland, 64 patients with AUD with MDD, 283 patients with AUD with clinically significant depressive symptoms at admission, and 81 patients with AUD with such problems at discharge were compared with patients with AUD only on alcohol use, depressive symptoms, and treatment service utilization. MDD was provisionally identified at admission and definitively defined at discharge. Whereas patients with MDD did not differ from patients with AUD only at 1-year follow-up, patients with AUD with clinically significant depressive symptoms had significantly shorter time-to-first-drink and a lower abstinence rate. These patients also had elevated AUD indices and treatment service utilization for psychiatric disorders. Our results suggest that clinically significant depressive symptoms are a substantial risk factor for relapse so that it may be important to treat them during and after residential AUD treatment programs.

Effects of the glucocorticoid antagonist, mifepristone, on the consequences of withdrawal from long term alcohol consumption

BACKGROUND: Studies were carried out to test the hypothesis that administration of a glucocorticoid Type II receptor antagonist, mifepristone (RU38486), just prior to withdrawal from chronic alcohol treatment, would prevent the consequences of the alcohol consumption and withdrawal in mice. MATERIALS AND METHODS: The effects of administration of a single intraperitoneal dose of mifepristone were examined on alcohol withdrawal hyperexcitability. Memory deficits during the abstinence phase were measured using repeat exposure to the elevated plus maze, the object recognition test, and the odor habituation/discrimination test. Neurotoxicity in the hippocampus and prefrontal cortex was examined using NeuN staining. RESULTS: Mifepristone reduced, though did not prevent, the behavioral hyperexcitability seen in TO strain mice during the acute phase of alcohol withdrawal (4 hours to 8 hours after cessation of alcohol consumption) following chronic alcohol treatment via liquid diet. There were no alterations in anxiety-related behavior in these mice at 1 week into withdrawal, as measured using the elevated plus maze. However, changes in behavior during a second exposure to the elevated plus maze 1 week later were significantly reduced by the administration of mifepristone prior to withdrawal, indicating a reduction in the memory deficits caused by the chronic alcohol treatment and withdrawal. The object recognition test and the odor habituation and discrimination test were then used to measure memory deficits in more detail, at between 1 and 2 weeks after alcohol withdrawal in C57/BL10 strain mice given alcohol chronically via the drinking fluid. A single dose of mifepristone given at the time of alcohol withdrawal significantly reduced the memory deficits in both tests. NeuN staining showed no evidence of neuronal loss in either prefrontal cortex or hippocampus after withdrawal from chronic alcohol treatment. CONCLUSIONS: The results suggest mifepristone may be of value in the treatment of alcoholics to reduce their cognitive deficits.

Cellular Photo Digital Breathalyzer for Monitoring Alcohol Use: A Pilot Study

Background: Monitoring alcohol use is important in numerous situations. Direct ethanol metabolites, such as ethyl glucuronide (EtG), have been shown to be useful tools in detecting alcohol use and documenting abstinence. For very frequent or continuous control of abstinence, they lack practicability. Therefore, devices measuring ethanol itself might be of interest. This pilot study aims at elucidating the usability and accuracy of the cellular photo digital breathalyzer (CPDB) compared to self-reports in a naturalistic setting. Method: 12 social drinkers were included. Subjects used a CPDB 4 times daily, kept diaries of alcohol use and submitted urine for EtG testing over a period of 5 weeks. Results: In total, the 12 subjects reported 84 drinking episodes. 1,609 breath tests were performed and 55 urine EtG tests were collected. Of 84 drinking episodes, CPDB detected 98.8%. The compliance rate for breath testing was 96%. Of the 55 EtG tests submitted, 1 (1.8%) was positive. Conclusions: The data suggest that the CPDB device holds promise in detecting high, moderate, and low alcohol intake. It seems to have advantages compared to biomarkers and other Monitoring devices. The preference for CPDB by the participants might explain the high compliance. Further studies including comparison with biomarkers and transdermal devices are needed.

Direct metabolites of Ethanol as biological markers of alcohol use: Basic aspects and applications

In addition to self reports and questionnaires, biomarkers are of relevance in the diagnosis of and therapy for alcohol use disorders. Traditional biomarkers such as gamma-glutamyl transpeptidase or mean corpuscular volume are indirect biomarkers and are subject to the influence of age, gender and non-alcohol related diseases, among others. Direct metabolites of ethanol such as Ethyl glucuronide (EtG), ethyl sulphate (EtS) and phosphatidylethanol (PEth) are direct metabolites of ethanol, that are positive after intake of ethyl alcohol. They represent useful diagnostic tools for identifying alcohol use even more accurately than traditional biomarkers. Each of these drinking indicators remains positive in serum and urine for a characteristic time spectrum after the cessation of ethanol intake - EtG and EtS in urine up to 7 days, EtG in hair for months after ethanol has left the body. Applications include clinical routine use, emergency room settings, proof of abstinence in alcohol rehabilitation programmes, driving under influence offenders, workplace testing, assessment of alcohol intake in the context of liver transplantation and foetal alcohol syndrome. Due to their properties, they open up new perspectives for prevention, interdisciplinary cooperation, diagnosis of and therapy for alcohol-related problems.

Comparison of direct and indirect alcohol markers with PEth in blood and Urine in alcohol dependent inpatients during detoxication

The importance of direct and indirect alcohol markers to evaluate alcohol consumption in clinical and forensic settings is increasingly recognized. While some markers are used to prove abstinence from ethanol, other markers are suitable for detection of alcohol misuse. Phosphatidyl ethanol (PEth) is ranked among the latter. There is only little information about the correlation between PEth and other currently used markers (ethyl glucuronide, ethyl sulfate, carbohydrate deficient transferrin, gamma-glutamyl transpeptidase, and methanol) and about their decline during detoxification. To get more information, 18 alcohol-dependent patients in withdrawal therapy were monitored for These parameters in blood and urine for up to 19 days. There was no correlation between the different markers. PEth showed a rapid decrease at the beginning of the intervention, a slow decline after the first few days, and could still be detected after 19 days of abstinence from ethanol.

What Ethanol metabolites as biological markers tell us about alcohol use

Alcohol and tobacco related disorders are the two leading and most expensive causes of illness in central Europe. In addition to self reports and questionnaires, biomarkers are of relevance in diagnosis and therapy of alcohol use disorders.Traditional biomarkers such as gamma glutamyl transpeptidase or mean corpuscualr volume are indirect biomarkers and are subject to influence of age, gender and non alcohol related diseases, among others.Direct ethanol metabolites such as ethyl glucuronide (EtG), ethyl sulphate (EtS) and phosphatidylethanol (PEth) are direct metabolites of ethanol, that are positive after intake of ethyl alcohol. They represent useful diagnostic tools for identifying alcohol use even more accurately than traditional biomarkers. Each of these drinking indicators remains positive in serum and urine for a characteristic time spectrum after the cessation of ethanol intake-EtG and EtS in urine up to 7 days, EtG in hair for months after ethanol has left the body. Applications include clinical routine use, emergency room settings, proof of abstinence in alcohol rehabilitation programs, driving under influence offenders, workplace testing, assessment of alcohol intake in the context of liver transplantation and fetal alcohol syndrome.

Motivation as a predictor of drinking outcomes after residential treatment programs for alcohol dependence

OBJECTIVES: Patients' motivation to change their substance use is usually viewed as a crucial component of successful treatment. The objective of this study was to examine whether motivation contributes to drinking outcomes after residential treatment for alcohol dependence. METHODS: Our sample included 415 Swiss patients from 12 residential alcohol treatment programs. We statistically controlled for important predictors, such as sex, employment, alcohol consumption before admission, severity of alcohol dependence, severity of psychiatric symptoms at admission, and alcohol-related self-efficacy at discharge. Abstinence, alcohol consumption, and time to first drink were used as primary outcome measures and were assessed 1 year after discharge from treatment. RESULTS: Action-oriented motivation to change substance use had a modest impact on drinking outcomes. At the 1-year follow-up, only the Taking Steps subscale of the Stages of Change Readiness and Treatment Eagerness Scale and alcohol-related self-efficacy were found to be significant predictors of abstinence and the number of standard drinks. CONCLUSIONS: The impact of action-oriented motivation at admission to residential treatment is modest but still relevant, compared with other outcome predictors. It may be useful to focus treatment on improving action-oriented motivation to reduce substance use

Association Between Drinking Goal and Alcohol Use One Year After Residential Treatment: A Multicenter Study

This study examined whether patients’ drinking goals at admission to and discharge from 12 residential alcohol use disorder treatment programs were associated with alcohol-related outcomes at 1-year follow-up. Detoxified patients (N D 289) completed assessments at admission, after treatment, and at 1-year follow-up. Drinking goals of abstinence, conditional abstinence (in principle abstinence but potential occurrence of lapses or drinking, when urges are strong), and controlled drinking changed during treatment and predicted the 1-year follow-up outcomes (abstinence, number of standard drinks, and number of days to the first alcohol use). Goals at discharge had a better predictive value. The goal of abstinence at discharge had better outcomes than conditional abstinence; the poorest had controlled drinking.

Resistance to Temptation: The Interaction of External and Internal Control on Alcohol Use During Residential Treatment for Alcohol Use Disorder

Background: There is evidence that drinking during residential treatment is related to various factors, such as patients’ general control beliefs and self-efficacy, as well as to external control of alcohol use by program’s staff and situations where there is temptation to drink. As alcohol use during treatment has been shown to be associated with the resumption of alcohol use after discharge from residential treatment, we aimed to investigate how these variables are related to alcohol use during abstinenceoriented residential treatment programs for alcohol use disorders (AUD). Methods: In total, 509 patients who entered 1 of 2 residential abstinence-oriented treatment programs for AUD were included in the study. After detoxification, patients completed a standardized diagnostic procedure including interviews and questionnaires. Drinking was assessed by patients’ selfreport of at least 1 standard drink or by positive breathalyzer testing. The 2 residential programs were categorized as high or low control according to the average number of tests per patient. Results: Regression analysis revealed a significant interaction effect between internal and external control suggesting that patients with high internal locus of control and high frequency of control by staff demonstrated the least alcohol use during treatment (16.7%) while patients with low internal locus of control in programs with low external control were more likely to use alcohol during Treatment (45.9%). No effects were found for self-efficacy and temptation. Conclusions: As alcohol use during treatment is most likely associated with poor treatment outcomes, external control may improve treatment outcomes and particularly support patients with low internal locus of control, who show the highest risk for alcohol use during treatment. High external control may complement high internal control to improve alcohol use prevention while in treatment. Key Words: Alcohol Dependence, Alcohol Use, Locus of Control, Alcohol Testing.