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Giovanni Addolorato

Publications and source records attributed to Giovanni Addolorato.

33 records · Page 2Linked to original sources
PubMed2004

Role of GABA(B) receptor in alcohol dependence: reducing effect of baclofen on alcohol intake and alcohol motivational properties in rats and amelioration of alcohol withdrawal syndrome and alcohol craving in human alcoholics.

The present paper describes the results of recent preclinical and clinical studies conducted in this laboratory in order to characterize the anti-alcohol properties of the GABA(B) receptor agonist, baclofen. At a preclinical level, the repeated administration of non-sedative doses of baclofen dose-dependently suppressed the acquisition and maintenance of alcohol drinking behavior in selectively bred Sardinian alcohol-preferring (sP) rats tested under the homecage, 2-bottle "alcohol vs water" choice regimen. Acute injection of baclofen completely blocked the temporary increase in voluntary alcohol intake occurring after a period of alcohol abstinence (the so-called alcohol deprivation effect, which models alcohol relapses in human alcoholics). Acute treatment with baclofen also dose-dependently suppressed extinction responding for alcohol (an index of motivation to consume alcohol) in sP rats trained to lever-press for oral alcohol self-administration. Taken together, these results suggest the involvement of the GABA(B) receptor in the neural substrate mediating alcohol intake and alcohol motivational properties in an animal model of excessive alcohol consumption. Further, acutely administered baclofen dose-dependently reduced the severity of alcohol withdrawal signs in Wistar rats made physically dependent upon alcohol. Preliminary clinical surveys suggest that the anti-alcohol properties of baclofen observed in rats may generalize to human alcoholics. Indeed, a double-blind survey demonstrated that repeated daily treatment with baclofen was associated, when compared to placebo, with a higher percentage of subjects totally abstinent from alcohol and a higher number of days of total abstinence. Treatment with baclofen also suppressed the number of daily drinks and decreased the obsessive and compulsive components of alcohol craving. Finally, a single non-sedative dose of baclofen resulted in the rapid disappearance of alcohol withdrawal symptomatology, including delirium tremens, in alcohol-dependent patients. In both clinical studies, baclofen was well tolerated with minimal side effects. These results suggest that baclofen may represent a potentially effective medication in the treatment of alcohol-dependent patients.

Alcohol Drinking↗
PubMed2003

Rapid regression of psoriasis in a coeliac patient after gluten-free diet. A case report and review of the literature.

BACKGROUND: Several skin disorders are present in patients affected by coeliac disease (CD) - among them, psoriasis has been described. However, at present the relationship between CD and psoriasis remains controversial since there are few and contrasting data on this topic. METHOD: Here we describe a case of psoriasis in a CD patient not responding to specific therapies for psoriasis. RESULT: The regression of skin lesions after gluten-free diet (GFD) was evident in a short time. CONCLUSION: The present case supports the association between CD and psoriasis and the concept that psoriasis in CD patients can be improved by GFD. Future studies are needed to clarify the possible mechanisms involved in this association.

Celiac Disease↗
PubMed2003

Evaluation of the albumin-gamma-glutamyltransferase isoenzyme as a diagnostic marker of hepatocellular carcinoma-complicating liver cirrhosis.

AIM: The present study aimed to evaluate the usefulness of albumin-gamma-glutamyltransferase isoenzyme in the diagnosis of hepatocellular carcinoma. METHODS: Electrophoretic assays of gamma-glutamyltransferase isoenzymes were performed on sera from 190 cirrhotics with (n = 131) or without (n = 59) hepatocellular carcinoma, 36 patients with chronic active hepatitis, 17 patients with liver metastases, and 16 control subjects. In the group of cirrhotic patients, the serum level of alpha-fetoprotein was also assessed. RESULTS: Albumin-gamma-glutamyltransferase was found in 88 of 131 cirrhotics with hepatocellular carcinoma, 14 of 59 cirrhotics without hepatocellular carcinoma, nine of 17 patients with liver metastases, and in none of the chronic active hepatitis or control patients. Within the cirrhotic subgroup, albumin-gamma-glutamyltransferase was effective in detecting hepatocellular carcinoma in general (sensitivity: 67%; specificity: 76%; diagnostic accuracy: 70%), and small hepatocellular carcinoma (< 3 cm; corresponding figures: 58, 76, and 69%). The best alpha-fetoprotein value discriminating between hepatocellular carcinoma and non-hepatocellular carcinoma cirrhotics was 20 ng/mL (sensitivity: 54%; specificity 85%; accuracy: 64%). The combined use of albumin-gamma-glutamyltransferase and alpha-fetoprotein, > 20 ng/mL, was associated with greater sensitivity and accuracy (84 and 74%, respectively) than those observed with either of the two markers considered alone. CONCLUSIONS: Albumin-gamma-glutamyltransferase appears to be a sensitive diagnostic marker of both advanced and small hepatocellular carcinoma-complicating liver cirrhosis.

Adolescent↗
PubMed2003

Association between migraine and Celiac disease: results from a preliminary case-control and therapeutic study.

OBJECTIVES: Subclinical celiac disease (CD) has been associated with various neurological disorders, the most common being neuropathy and cerebellar ataxia. The aims of the present study were to assess the following: 1) the prevalence of CD in patients affected by migraine; 2) whether there are regional cerebral blood flow abnormalities in migraine patients with CD compared to migraine patients without CD; and 3) the effects of a gluten free diet in migraine patients with CD. METHODS: A total of 90 patients affected by idiopathic migraine were enrolled, and 236 blood donors were used as controls. Serum IgG antitransglutaminase (TgA) and IgA antiendomysial (EmA) were measured. In positive cases, diagnosis was confirmed endoscopically. A gluten free diet was started in the patients diagnosed with CD, who were followed for 6 months. A single photon emission CT brain study was performed before and after a gluten free diet. RESULTS: Four of 90 (4.4%; 95% CI = 1.2-11.0) migraine patients were found to have CD compared with 0.4% (95% CI = 0.01-2.3) blood donor controls (p < 0.05). During the 6 months of gluten free diet, one of the four patients had no migraine attacks, and the remaining three patients experienced an improvement in frequency, duration, and intensity of migraine. Single photon emission CT studies showed a regional baseline reduction in brain tracer uptake in all four patients. Such reduction in uptake completely resolved at follow-up. CONCLUSIONS: Our results suggest that a significant proportion of patients with migraine may have CD, and that a gluten free diet may lead to a improvement in the migraine in these patients.

Adult↗
PubMed2002

Metadoxine in acute alcohol intoxication: a double-blind, randomized, placebo-controlled study.

BACKGROUND: At present there are only intriguing and preliminary clinical results regarding the efficacy of metadoxine (pyridoxol L-2-pyrrolidone-5-carboxylate) in acute alcohol intoxication. The present study was planned with the aim of investigating the effectiveness of metadoxine in the management of patients affected by acute ethanol intoxication. METHODS: A double-blind, randomized, multicenter, placebo-controlled trial was carried out on 58 patients of both sexes with acute ethanol intoxication. Patients were treated with a single dose of 900-mg intravenous metadoxine (n = 29) or with placebo (n = 29). Patients were clinically and biochemically evaluated at 0.5, 1, 2, 3, 6, 9, and 12 hr after treatment. RESULTS: Treatment with metadoxine significantly decreased the half-life of ethanol in blood (from 6.70 +/- 1.84 to 5.41 +/- 1.99 hr; p < 0.013) and showed a faster rate of ethanol elimination. The effects on ethanol half-life in blood were accompanied by a faster onset of recovery from intoxication, defined as the time of the transition of blood ethanol levels to the immediately lower range defined by intoxication categories (in g/liter: 0 to 0.5, absent; 0.51 to 1.0, mild; 1.1 to 2.5, moderate; >2.5, severe). Thus the median time to onset of recovery was 0.95 hr with metadoxine and 2.34 hr with placebo (p = 0.013). The effects of treatment on blood alcohol levels were paralleled by a significant decrease in the rating of the toxic clinical symptomatology. At 2 hr the improvement of toxic symptoms (in percent of maximum possible) was 68 +/- 28 vs. 44 +/- 27% in controls (p < 0.002). CONCLUSIONS: In patients with acute ethanol intoxication metadoxine accelerated the elimination of ethanol from blood, which led to faster recovery from intoxication, and improved the behavioral toxic symptomatology. Metadoxine could be helpful in the management of acute ethanol intoxication.

Adult↗
PubMedDate not supplied

Primary renal angiosarcoma: a rare malignancy. A case report and review of the literature.

Angiosarcoma is a rare malignant tumor occurring in less than 2% of soft tissue sarcomas. Angiosarcoma involving the kidney usually represents metastasis from skin or visceral primary lesions, while angiosarcoma primarily occurring in the kidney is a very rare neoplasm. In the English literature, from 1942 to the present, only 19 cases of primary kidney angiosarcoma have been reported. A case of primary renal angiosarcoma presenting as a large kidney mass and flank pain occurring after traumatism is reported. The present case represents further evidence of a rare malignancy.

Hemangiosarcoma↗
PubMedDate not supplied

The GABA(B) receptor agonists baclofen and CGP 44532 prevent acquisition of alcohol drinking behaviour in alcohol-preferring rats.

AIMS: The present study investigated the effect of the gamma-aminobutyric acid (GABA)(B) receptor agonists, baclofen and CGP 44532, on the acquisition of alcohol drinking behaviour in selectively bred Sardinian alcohol-preferring (sP) rats. METHODS: Baclofen [0, 1 and 3 mg/kg, intraperitoneally (i.p.)] and CGP 44532 (0, 0.1, 0.3 and 1 mg/kg, i.p.) were administered immediately before alcohol presentation to alcohol-naive sP rats. Alcohol was offered under the two-bottle free-choice regimen with unlimited access for 24 h/day. Drug treatment was repeated once daily for 10 consecutive days. RESULTS: Baclofen and CGP 44532, dose-dependently and with comparable efficacy, suppressed alcohol intake; compensatory increases in water intake left total fluid intakes virtually unchanged. CONCLUSIONS: These results demonstrate that baclofen and CGP 44532 prevent the acquisition of alcohol drinking behaviour in sP rats, and suggest the involvement of the GABA(B) receptor in the mechanisms underlying the disclosure and experience of the reinforcing properties of alcohol in this rat line.

Alcohol Drinking↗
PubMedDate not supplied

Baclofen efficacy in reducing alcohol craving and intake: a preliminary double-blind randomized controlled study.

AIMS: The gamma-aminobutyric acid (GABA(B)) receptor agonist, baclofen, has recently been shown to reduce alcohol intake in alcohol-preferring rats and alcohol consumption and craving for alcohol in an open study in humans. The present study was aimed at providing a first evaluation of the efficacy of baclofen in inducing and maintaining abstinence and reducing craving for alcohol in alcohol-dependent patients in a double-blind placebo-controlled design. METHODS: A total of 39 alcohol-dependent patients were consecutively enrolled in the study. After 12-24 h of abstinence from alcohol, patients were randomly divided into two groups. Twenty patients were treated with baclofen and 19 with placebo. Drug and placebo were orally administered for 30 consecutive days. Baclofen was administered at the dose of 15 mg/day for the first 3 days and 30 mg/day for the subsequent 27 days, divided into three daily doses. Patients were monitored as out-patients on a weekly basis. At each visit alcohol intake, abstinence from alcohol, alcohol craving and changes in affective disorders were evaluated. RESULTS: A higher percentage of subjects totally abstinent from alcohol and a higher number of cumulative abstinence days throughout the study period were found in the baclofen, compared to the placebo, group. A decrease in the obsessive and compulsive components of craving was found in the baclofen compared to the placebo group; likewise, alcohol intake was reduced in the baclofen group. A decrease in state anxiety was found in the baclofen compared to the placebo group. No significant difference was found between the two groups in terms of current depressive symptoms. Baclofen proved to be easily manageable and no patient discontinued treatment due to the presence of side-effects. No patient was affected by craving for the drug and/or drug abuse. CONCLUSIONS: Baclofen proved to be effective in inducing abstinence from alcohol and reducing alcohol craving and consumption in alcoholics. With the limits posed by the small number of subjects involved, the results of this preliminary double-blind study suggest that baclofen may represent a potentially useful drug in the treatment of alcohol-dependent patients and thus merits further investigations.

Adult↗
PubMedDate not supplied

Suppression of alcohol delirium tremens by baclofen administration: a case report.

Delirium tremens (DT) is a clinical condition that appears in some patients affected by severe alcohol withdrawal syndrome (AWS). DT represents a serious complication, being characterized by elevated morbidity and mortality. Benzodiazepines are presently the drug of choice; however their use is related to several side effects. Baclofen is a stereoselective gamma-aminobutyric acid (GABAB) receptor agonist. Recent studies show that baclofen is able to suppress alcohol withdrawal symptoms. At present there are no data on the effects of baclofen administration in AWS complicated by DT. Here, we report a case of DT successfully treated with baclofen. This result indicates that the efficacy of baclofen in the treatment of DT should be examined in future clinical trials.

Adult↗
PubMedDate not supplied

Suppression of craving for gamma-hydroxybutyric acid by naltrexone administration: three case reports.

Gamma-hydroxybutyric acid (GHB) is currently used to induce and maintain abstinence from alcohol. Cases of craving and desire to increase doses of GHB have been reported in both clinical trials and nonclinical self-administration. The enhancement of dopamine activity induced by GHB receptor activation might play a role in the euphoric effect and potential craving and the consequent abuse of this drug. Naltrexone (NTX), a mu-opioid antagonist, is effective in inducing and maintaining abstinence from alcohol, reducing relapses in heavy drinking and craving for alcohol in alcohol-dependent outpatients. Taking into account the alcohol antireward property of NTX, we tested its activity in reducing craving for GHB in 3 consecutive cases of alcoholics who manifested craving for this drug. In all patients the combination with NTX suppressed the craving for GHB. The antireward effect of NTX likely results from its interference with the GHB-induced dopamine release, leading to a partial blockade of the GHB reinforcing effect responsible of the craving for the drug. A combined therapy with GHB and NTX seems to be able to suppress craving for the former, thus improving the manageability and safety of treatment.

Adult↗