Background: Four fractions of gamma-glutamyltransferase (GGT) with different molecular weight (b-, m-, sand nd f-GGT) are present in human plasma. Differential GGT fraction pattern is found in non-alcoholic liver disease (NAFLD) and chronic viral hepatitis, characterized by normal or decreased b-GGT/s-GGT (b/s) ratio, respectively. Methods: Chromatographic fractional GGT analysis was performed on plasma obtained from 51 subjects: 27 alcoholics (mean (SD), age 45 (9) years; 23 males; 14 positive for viral infection), 24 abstinents from at least 1 month (43 (12) years; 20 males; 6 positive for viral infection). Twenty-seven blood donors matched for age and gender (44 (9) years; 23 males) were selected as controls. Results: All fractions were significantly increased in alcoholics (P < 0.001), s-GGT showing the largest increase, while only m-GGT and s-GGT were elevated in abstainers (P < 0.01), in comparison with controls. The b/s ratio was significantly lower in both alcoholics and abstainers than in controls (median (25th-75th perc.

The endogenous production of NO provides significant myocardial protection from IR injury and histamine release. These effects were mimicked by various NO donors.

Our pilot study indicates that cocaine craving decreases with both aripiprazole and ropinirole treatment but aripiprazole is more efficacious in reducing cocaine use.

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To date, there is no pharmacological therapy with established efficacy for the treatment of cocaine dependence. Recent reviews 1,2 indicated that pharmacological agents such as GABA agents (topiramate, tiagabine, baclofen, and vigabatrin) and agonist replacement agents (modafinil, disulfiram, and methylphenidate) seem to be promising in treatment of cocaine dependence, but evidences are still inconclusive.Ropinirole is a dopamine agonist active on D 2 , D 3 , and D 4 receptors efficacious in the treatment of Parkinson's disease. 3 Only a pilot open-label trial has supported the efficacy and safety of ropinirole in the treatment of cocaine dependence. 4 Aripiprazole is an atypical antipsychotic drug characterized by partial agonist activity at D 2 and D 3 receptors and a low side-effect profile. Evidence from the literature 1,5,6 suggests that aripiprazole might modulate the dopaminegic firing in the brain caused by cocaine.We carried out a phase-II study in patients with cocaine dependence at seven Drug Addiction Services to determine the safety, tolerability, and the effects of aripiprazole and ropinirole in patients with cocaine dependence. The study protocol was approved by the Bioethics Committees of Pisa (the coordinating center) and of the other participating centers; all patients signed a written informed consent to participate.Participants were randomly assigned to aripriprazole or ropinirole treatment for 12 weeks.Aripiprazole was administered once daily at the dosage of 5 mg/day in the first week, then at 10 mg/day from week 2 to 12. Ropinirole was begun at 0.75 mg/day (three times a day) during the first week and then titrated to 1.5 mg/day (three times a day) from week 2 to 12.The Clinical Global Impression Scale (CGIS), a Visual Analogue Scale to assess the craving, and a self-report questionnaire on the use of cocaine were administered at baseline and then weekly throughout the study. Toxicology screening urinalysis was collected three times per week and analyzed using immunoenzymatic procedures.Vital signs were examined weekly and laboratory tests were carried out at baseline and at endpoint.No psychotherapy was carried out during the study because of its potential confounding effect.The outcomes were: craving intensity, CGI improvement at endpoint, mean weekly consumption of cocaine (in grams), mean number of weekly administrations of cocaine, and positive urine samples. Each outcome was analyzed using linear mixed-effects models. Of the 28 participants (22 males, 6 females, mean age 33.4 years, SD = 6.8, range 22-51), 14 completed the study. Treatment discontinuation was unrelated with side effects. Blood tests did not change significantly from baseline to endpoint. The intensity of craving, measured from 0 to 100 on a Visual Analogue Scale, decreased on average 35 percentage points in patients treated with aripiprazole, and 22 points in patients treated with ropinirole; the mean weekly cocaine use decreased from 6.2 ± 8.0 g to 0.6 ± 0.7 g in the aripiprazole group and 5.4 ± 4.2 g to 1.8 ± 1.0 g ...