• Energy Research

Background: Benzodiazepine has been shown to be one of the most effective class of drugs in the management of alcohol withdrawal syndrome (AWS). Gamma‐hydroxybutyric acid (GHB) has recently been introduced in the treatment of alcohol problems, including AWS. At present there are no comparative studies between benzodiazepines and GHB in AWS treatment. The aim of the present randomized, controlled, single‐blind study was to evaluate the efficacy and safety of GHB compared with diazepam in the treatment of AWS.Methods: Sixty alcoholics affected by AWS were enrolled in the study. Diazepam (0.5–0.75 mg/kg body weight for 6 days, tapering the dose 25% daily until day 10) was administered orally to 30 patients (25 males, 5 females; mean age 44.3 ± 10.9 years); GHB (50 mg/kg body weight for 10 days) was administered orally to 30 patients (26 males, 4 females; mean age 41.7 ± 10.4 years). The Clinical Institute Withdrawal Assessment for Alcohol‐revised scale (CIWA‐Ar) was used to evaluate the AWS physical symptoms. The State Anxiety Inventory test for current anxiety assessment and the Zung self‐rating Depression Scale for current depression assessment were performed.Results: Eight patients (26.6%) in the diazepam group and 4 patients (13.3%) in the GHB group dropped out. Both treatments were effective in reducing AWS. No significant difference was found between the groups in CIWA‐Ar total score at baseline and at the different times of observation. Considering the CIWA‐Ar subscore and Zung scale, a significant reduction of anxiety on day 4 (p< 0.02), agitation on day 5 (p< 0.02) and time of recovery of depression on day 5 (p< 0.02) was observed in the GHB group with respect to the diazepam group. Drowsiness and vertigo developed after initial drug administration in the GHB (19.2%) and diazepam (36.4%) groups and quickly resolved in both groups.Conclusions: GHB is as effective in the management of AWS as benzodiazepine and it seems to be quicker in reducing anxiety, agitation, and depression. Both drugs are safe and well‐tolerated in AWS management.

Background: Benzodiazepine has been shown to be one of the most effective class of drugs in the management of alcohol withdrawal syndrome (AWS). Gamma‐hydroxybutyric acid (GHB) has recently been introduced in the treatment of alcohol problems, including AWS. At present there are no comparative studies between benzodiazepines and GHB in AWS treatment. The aim of the present randomized, controlled, single‐blind study was to evaluate the efficacy and safety of GHB compared with diazepam in the treatment of AWS.Methods: Sixty alcoholics affected by AWS were enrolled in the study. Diazepam (0.5–0.75 mg/kg body weight for 6 days, tapering the dose 25% daily until day 10) was administered orally to 30 patients (25 males, 5 females; mean age 44.3 ± 10.9 years); GHB (50 mg/kg body weight for 10 days) was administered orally to 30 patients (26 males, 4 females; mean age 41.7 ± 10.4 years). The Clinical Institute Withdrawal Assessment for Alcohol‐revised scale (CIWA‐Ar) was used to evaluate the AWS physical symptoms. The State Anxiety Inventory test for current anxiety assessment and the Zung self‐rating Depression Scale for current depression assessment were performed.Results: Eight patients (26.6%) in the diazepam group and 4 patients (13.3%) in the GHB group dropped out. Both treatments were effective in reducing AWS. No significant difference was found between the groups in CIWA‐Ar total score at baseline and at the different times of observation. Considering the CIWA‐Ar subscore and Zung scale, a significant reduction of anxiety on day 4 (p< 0.02), agitation on day 5 (p< 0.02) and time of recovery of depression on day 5 (p< 0.02) was observed in the GHB group with respect to the diazepam group. Drowsiness and vertigo developed after initial drug administration in the GHB (19.2%) and diazepam (36.4%) groups and quickly resolved in both groups.Conclusions: GHB is as effective in the management of AWS as benzodiazepine and it seems to be quicker in reducing anxiety, agitation, and depression. Both drugs are safe and well‐tolerated in AWS management.

Increasing evidence suggests that alcohol abuse may be linked to adverse immunomodulatory effects on immune responses. Our study was undertaken to clarify the immunological consequences of chronic and acute alcohol exposure on differentiation and maturation of human dendritic cells (DCs). Using immunochemical and cytofluorimetric analysis we determined the phenotype and functions of monocyte-derived DCs from alcoholics and healthy subjects and analyzed their ability to respond to lipopolysaccharide (LPS) in the presence or absence of ethanol (EtOH) exposure. Our results showed that alcoholics' monocytes differentiated to immature DCs with altered phenotype and functions (alc-iDCs). Alc-iDCs showed fewer CD1a+ cells, weaker CD86 expression and higher HLA-DR expression associated with lower endocytosis and allostimulatory functions than iDCs from healthy subjects (control-iDCs). Despite these impairments, alc-iDCs produced TNF-α and IL-6 in large amounts. LPS stimulation failed to induce full phenotypical and functional alc-iDC maturation. In vitro acute EtOH exposure also prevented alc-iDCs and control-iDCs from maturing in response to LPS. T-cell priming experiments showed that EtOH treatment prevented LPS-stimulated control-iDCs from priming and polarizing naïve allogeneic T cells into Th1 cells, thus favouring a predominant Th2 environment. Collectively, our results provide evidence that chronic and acute alcohol exposure prevents DCs from differentiating and maturing in response to a microbial stimulus.

Increasing evidence suggests that alcohol abuse may be linked to adverse immunomodulatory effects on immune responses. Our study was undertaken to clarify the immunological consequences of chronic and acute alcohol exposure on differentiation and maturation of human dendritic cells (DCs). Using immunochemical and cytofluorimetric analysis we determined the phenotype and functions of monocyte-derived DCs from alcoholics and healthy subjects and analyzed their ability to respond to lipopolysaccharide (LPS) in the presence or absence of ethanol (EtOH) exposure. Our results showed that alcoholics' monocytes differentiated to immature DCs with altered phenotype and functions (alc-iDCs). Alc-iDCs showed fewer CD1a+ cells, weaker CD86 expression and higher HLA-DR expression associated with lower endocytosis and allostimulatory functions than iDCs from healthy subjects (control-iDCs). Despite these impairments, alc-iDCs produced TNF-α and IL-6 in large amounts. LPS stimulation failed to induce full phenotypical and functional alc-iDC maturation. In vitro acute EtOH exposure also prevented alc-iDCs and control-iDCs from maturing in response to LPS. T-cell priming experiments showed that EtOH treatment prevented LPS-stimulated control-iDCs from priming and polarizing naïve allogeneic T cells into Th1 cells, thus favouring a predominant Th2 environment. Collectively, our results provide evidence that chronic and acute alcohol exposure prevents DCs from differentiating and maturing in response to a microbial stimulus.

Serum mitochondrial and total aspartate aminotransferase activity was quantified by a characterized immunochemical method in 126 subjects, 44 healthy controls and 82 chronic alcoholics (51 outpatients and 31 monitored through 15 days). The monitored alcoholics were divided into actual abstinents (n = 21) and drinkers (n = 10) by blood ethanol concentration performed daily. The aims of the present study were: (a) to compare the diagnostic diagnostic usefulness of the mitochondrial isoenzyme and the mitochondrial/total aspartate aminotransferase ratio to detect problematic drinkers; (b) to evaluate the suitability of these indices to monitor abstinence, a difficulty not yet solved in the clinical management of alcoholics. The results demonstrated the mitochondrial isoenzyme to be more suitable to discriminate between controls and alcoholics (Kruskal and Wallis ANOVA, Bonferroni test, P < 10(-5) and mostly between actual drinkers and other alcoholics (P < 0.041). So acute alcohol consumption may be a significant, suggestive and until now inadequately examined factor in evaluating the suitability of mAST as a marker. The results, showing that mAST peaks quickly appear in the presence of a new alcohol intake, should indicate mAST as a possible marker of acute alcohol intake useful in checking self-claimed abstinence.

Serum mitochondrial and total aspartate aminotransferase activity was quantified by a characterized immunochemical method in 126 subjects, 44 healthy controls and 82 chronic alcoholics (51 outpatients and 31 monitored through 15 days). The monitored alcoholics were divided into actual abstinents (n = 21) and drinkers (n = 10) by blood ethanol concentration performed daily. The aims of the present study were: (a) to compare the diagnostic diagnostic usefulness of the mitochondrial isoenzyme and the mitochondrial/total aspartate aminotransferase ratio to detect problematic drinkers; (b) to evaluate the suitability of these indices to monitor abstinence, a difficulty not yet solved in the clinical management of alcoholics. The results demonstrated the mitochondrial isoenzyme to be more suitable to discriminate between controls and alcoholics (Kruskal and Wallis ANOVA, Bonferroni test, P < 10(-5) and mostly between actual drinkers and other alcoholics (P < 0.041). So acute alcohol consumption may be a significant, suggestive and until now inadequately examined factor in evaluating the suitability of mAST as a marker. The results, showing that mAST peaks quickly appear in the presence of a new alcohol intake, should indicate mAST as a possible marker of acute alcohol intake useful in checking self-claimed abstinence.

Hypertension is an established risk factor in chronic alcoholics, but little is known about the relationship between blood pressure (BP), severity of their alcohol abuse, and severity of alcohol withdrawal syndrome (AWS).BP was assessed daily for 18 days in a series of chronic alcoholics on early alcohol withdrawal (AW), while also assessing the severity of their AWS on the CIWA-Ar scale.A sharp and sustained decrease in BP was observed after AW; at T0, BP had increased in 55% of patients, and at T18 in 21%. The variation of BP is partially explained by years of at-risk drinking and AWS severity, but other factors may play a role in hypertension in alcoholics, as a large amount of BP variation was not explained by the alcohol-abuse-related parameters that we studied. BP values were not correlated with cigarette smoking, anxiety, or depression. Hypertension found in 'detoxified' alcoholics (approximately 20%) may be related to alcohol-independent hypertension or to a long-lasting alcohol-induced derangement of the BP regulating mechanisms. Further research is needed in these patients to elucidate the mechanisms of persistent hypertension and to set up a treatment protocol. At present, careful monitoring is advisable, as well as pharmacological treatment for moderate or severe hypertension; often a modification of life-style is needed which includes physical activity and possibly sodium (Na) restriction, since hypertension in detoxified alcoholics seems to be Na sensitive.Complete alcohol abstinence must be recommended to all hypertensive alcoholics, as AW-induced transient hypertension was found to be harmless in all our subjects, and abstinence leads to a complete recovery from hypertension in most cases.