Alcoholism, clinical and experimental research
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The exact enzymatic mechanisms of ethanol oxidation in the brain are still unclear. The catalase-mediated oxidation of ethanol was demonstrated in rat brain using incubation of brain homogenates with catalase inhibitors. The role of the alcohol dehydrogenase (ADH) or cytochrome P450-dependent system in this process is possible, but has not been confirmed. The objective of the study was to determine the contribution of the different enzymatic pathways to ethanol oxidation in brain homogenates from mice and rats. ⋯ Catalase is the key enzyme of ethanol oxidation in the brain of rodents: it may be responsible for about 60% of the process. CYP2E1 plays an important role in ethanol oxidation in the rodent brains. Alcohol dehydrogenase plays a minor role, if any, in this process. Aldehyde dehydrogenase plays the crucial role in the further oxidation of ethanol-derived AC in the brain homogenates.
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Alcohol. Clin. Exp. Res. · Jun 2006
Cold pressor task reactivity: predictors of alcohol use among alcohol-dependent individuals with and without comorbid posttraumatic stress disorder.
The association between stress and alcohol dependence has been well established. Abnormalities in stress reactivity and hypothalamic-pituitary-adrenal axis (HPA) function may be involved in the mechanistic connection between stress and the initiation, development, and/or maintenance of alcohol dependence. Posttraumatic stress disorder (PTSD) commonly co-occurs with alcohol dependence and is characterized by HPA axis abnormalities. This study investigated the relationship between subjective and neuroendocrine stress reactivity to the cold pressor task (CPT) and prospective alcohol use among individuals with alcohol dependence, with and without comorbid PTSD. ⋯ These preliminary findings demonstrate significant differences between the alcohol-only and the alcohol/PTSD group in predictors of relapse. For the alcohol-only group, reactivity to an acute laboratory stressor may be predictive of subsequent alcohol use. This was not true for the alcohol/PTSD group. Although preliminary, the findings may help shed light on the mechanistic relationship between stress reactivity and increased risk for alcohol relapse and dependence in individuals with and without other Axis I comorbidity.
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Alcohol. Clin. Exp. Res. · Mar 2006
Randomized Controlled Trial Comparative StudySingle- and multiple-dose pharmacokinetics of long-acting injectable naltrexone.
Oral naltrexone is effective in the treatment of alcohol dependence; however, a major limitation of its clinical utility is poor patient adherence to the daily dosing schedule. A biodegradable, long-acting naltrexone microsphere formulation was developed to achieve continuous naltrexone exposure for 1 month in the treatment of alcohol dependence. ⋯ This study demonstrated that the long-acting naltrexone formulation was well tolerated, displayed predictable pharmacokinetics, and resulted in no meaningful drug accumulation upon multiple dosing. Intramuscular administration avoids first-pass metabolism and changes the exposure ratio of 6beta-naltrexol to naltrexone compared with oral administration. By providing continuous exposure to naltrexone for several weeks following IM injection, this long-acting naltrexone formulation may offer therapeutic benefit to those patients who experience difficulty adhering to the daily administration schedule necessitated by oral naltrexone therapy.
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Alcohol. Clin. Exp. Res. · Feb 2006
Comparative StudyChallenges applying alcohol brief intervention in diverse practice settings: populations, outcomes, and costs.
This article summarizes the proceedings of a symposium at the 2005 Research Society on Alcoholism, Santa Barbara, California. The purpose of the symposium was to address challenges that arise in translating evidence for efficacy of alcohol brief intervention (BI) into diverse clinical settings and populations by reviewing the literature and describing 4 research studies. Dr. ⋯ Kraemer presented results of a decision analytic and computer-simulation model regarding the cost-effectiveness of alcohol screening and intervention in primary care settings. Finally, Dr. Perl discussed the salient issues and suggested future directions for work in the area of alcohol BI.
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Alcohol. Clin. Exp. Res. · Jan 2006
Dispersion of the corrected QT and JT interval in the electrocardiogram of alcoholic patients.
The aim of this study was to analyze the corrected QT interval (QTc), its dispersion (QTcd), and the QT interval index (QTcI) and to compare it with the corrected JT interval (JTc), its dispersion (JTcd), and the JT interval index (JTcI) in long-term alcoholic users, by investigating the ventricular activation until the completion of repolarization. ⋯ Persons who consume various alcoholic beverages excessively and for a long time have significantly higher dispersions of the QTc and JTc, intervals and they have a significantly higher estimation of relative risk for the prolonged QTc interval and higher QTc dispersion than the control group, i.e., higher risk of arrhythmias.