Effects of moderate and high doses of alcohol on carotid atherogenesis.

The role of alcohol consumption on pathophysiology of atherosclerosis is not completely well established. Past studies were conducted with different methodological approaches, sometimes leading to opposing conclusions. The aim of this study was to determine the weight of alcohol intake on carotid atherosclerosis in a group of subjects asymptomatic for cardio-cerebrovascular diseases. They were examined by ultrasonographic assessment during the period 1993 through 1997. Common risk factors of atherosclerosis and drinking habit were assessed by a standardized questionnaire. In this survey we confirm the J-shaped relationship between atherosclerosis and alcohol consumption. The effect of alcohol intake is more evident if we consider the presence of multiple internal carotid stenosis, or those greater than 25%, as outcome variables. These effects are independent from the other risk factors included in logistic regression paradigms (age, arterial hypertension, dyslipidemia, diabetes mellitus, family history of cardio-cerebrovascular disease, smoking and social status). Our study supported that a high level of alcohol intake plays a role as an independent factor in carotid atherogenesis.

Cognitive impairment and cerebral atrophy in "heavy drinkers".

1. Aim of the work was to verify the following three hypotheses in alcoholics: a) right hemisphere; b) diffuse brain deficit; c) anterior brain deficit, by means of a neuropsychological and a neuroradiological assessment. 2. 15 alcoholic right-hand male subjects and 15 matched controls were enrolled in the study. 3. Specifically designed neuropsychological testing was performed to investigate logical abilities, selective attention and memory. 4. Neurological investigation was performed by a standard CT scan to assess the degree and localization of brain damage. 5. Alcoholics performed worse than controls on some neuropsychological tests, i.e. Attention Matrices Test, Verbal Judgement Test, Forward Digit Span, Story Recall and Remote Memory Test. The analysis of variance adjusted by the attentional score showed no significant differences between alcoholics and controls. 6. Neuroradiological data showed a preeminent and a more frequent atrophy of the frontal region. 7. No correlations emerged between neuropsychological and neuroradiological data. 8. In conclusion, the hypothesis of anterior brain deficit seems to be confirmed by our study.

The effects of flumazenil on focal, electroinduced after-discharge in rabbits.

1. The anticonvulsive efficacy of flumazenil 10 mg/kg i.v., a BDZ antagonist, was studied in two models of experimental epilepsy electrically induced. 2. The EEG after-discharge, which was induced by the electrical stimulation of selected brain regions [(notably the dorsal hippocampus (Hip) and the amygdala (CAm)] was evaluated in rabbits pre- and post-drug administration. 3. In the animals submitted to electrical stimulation of the amygdala, flumazenil exerted a protective action, thereby inducing an increase in the after-discharge threshold and/or a decrease in after-discharge duration. 4. In the animals submitted to electrical stimulation of the hippocampus, flumazenil did not induced changes statistically significant. 5. Finally, the paper discusses the two possible mechanisms of action of flumazenil (a "per se" partial BDZ activity and/or a BDZ agonistic activity, which displaces the inverse agonist-like ligand) and the differencies in GABA distribution in the hippocampus and the amygdala.

Role of dopamine D-1 and D-2 antagonists in a model of focal epilepsy induced by electrical stimulation of hippocampus and amygdala in the rabbit.

1. The differential role played by blockade of D-1 or D-2 dopamine receptors in mechanisms underlying seizures was studied in a model of EEG after-discharge induced by electrical stimulation of selective brain regions (dorsal hippocampus and amygdala) in the rabbit. 2. The D-2 antagonist haloperidol (1 mg/Kg) increased significantly after-discharge duration after stimulation of either hippocampus or amygdala and lowered after-discharge threshold in few animals. 3. The D-1 antagonist SCH 23390 (0.3 mg/Kg) caused no changes following stimulation of amygdala and reduced after-discharge duration when hippocampus was stimulated. 4. Haloperidol exerted a proconvulsant action in this experimental model, having a clearer influence on D-2 receptors. SCH 23390 had no effect on amygdala whereas it exerted protection on the hippocampus. 5. The present data suggest that D-1 and D-2 receptors have different roles in generating and spreading the epileptic activity.

Familial hemiplegic migraine versus migraine with prolonged aura: an uncertain diagnosis in a family report.

Four of five members of a family complained of repeated attacks of hemiplegic migraine, migraine with aura of different types, or migraine without aura. The hemiplegia always outlasted the headache and was often accompanied by altered consciousness, aphasia, and, in one patient, coma; in this latter patient, the ictal EEG, recorded during two attacks, showed delta activity in the hemisphere contralateral to the hemiplegia. At least 2 months after their latest attacks, three patients showed dyscalculia, attentional disturbances, and impaired long-term verbal memory on neuropsychologic assessment. There were no cognitive disturbances in the unaffected relative. The severity of cognitive impairment appears to be correlated with migraine history. We attempt to classify these cases according to the criteria of the International Headache Society.

Melatonin and cortisol circadian secretion during ethanol withdrawal in chronic alcoholics.

Changes in central neurotransmission and in hypothalamo-pituitary function occur in both ethanol (ETOH) intake and withdrawal. Melatonin (MLT) secretion is regulated by the noradrenergic system, which is activated upon ETOH withdrawal. Experimental evidence exist that pineal gland may have a role in ETOH intake and preference in rats. Twenty-four hour urinary excretion of MLT was found to be increased during ETOH intake in chronic alcoholics. In this study we have determined 24h plasma levels of MLT and cortisol in 8 chronic alcoholic males hospitalized for a detoxication program and in 8 healthy controls. The study was performed just after admission, on the first day of ETOH withdrawal and after 14 days of controlled abstinence. Circadian periodicity has been evaluated by the cosinor method. The initial determinations corresponded to the acute withdrawal phase. Twenty-four hour plasma MLT mean levels on acute withdrawal were higher than after 14 days abstinence and than those found in controls. Large interindividual differences prevented the detection of statistical significance. The cosinor analysis disclosed the loss of circadian periodicity in the acute withdrawal. Significant 24h periodicity was restored after 14 days abstinence. Cortisol levels were significantly higher than those found on day 14 and in healthy controls. Twenty-four hour periodicity was maintained in both alcoholics series. A delay in cortisol acrophase occurred in acute withdrawal. The effects of Corticotropin Releasing Hormone infusion on cortisol secretion were significantly enhanced in the acute withdrawal phase in comparison with those occurring when patients were retested and with healthy controls.

[Role of the dopaminergic system in experimental models of epilepsy]. / Ruolo del sistema dopaminergico in modelli di epilessia sperimentale.

It has been shown that neuroleptics which interact selectively with either D-1 or D-2 dopamine receptors possess a marked difference in their propensity on seizures. The aim of this work was to investigate whether the D-1 antagonist SCH 23390 differs from haloperidol (D-2 antagonist) in models of experimental epilepsy induced by electrical stimulation of selected brain regions (hippocampus and amygdala), in rabbits. Haloperidol increased and SCH 23390 significantly decreased the susceptibility to seizures in both models investigated. The data suggest that the D-1 and D-2 receptor subtypes have different roles in the mechanisms underlying seizures.

Antagonism of EEGraphic and behavioural effects of methamphetamine by selective receptor blockers (SCH 23390 and raclopride) in the rabbit.

1. The interactions between selective D1 and D2 antagonists (SCH 23390 and raclopride) and methamphetamine on EEG arousal and behaviour was studied in rabbits. Haloperidol, a "classic neuroleptic" was used as reference drug. 2. Both 23390 and raclopride, which were used at low dosage (0.03-0.09 mg/kg i.v. for the former and 1-3 mg/kg for the latter), were able to block completely the behaviour induced but do not inhibit completely the EEG arousal pattern induced by methamphetamine. 3. The blockade of both behaviour and EEG arousal took only when the two drugs were administered concomitantly at the lower dosage. 4. The antagonistic effects obtained with the concomitantly administration of the two drugs were of higher degree in confront of those obtained with the pretreatment with haloperidol 0.3 mg/kg i.v. 5. Our data indicate that both D1 and D2 antagonists are able to block, at the dosage used, motor hyperactivity and stereotyped behaviour typically induced by methamphetamine and that SCH 23390 and raclopride are potentiated also in this experimental model.