Synthesis and biological assessment of 3,7-dihydroxytropolones.

3,7-Dihydroxytropolones (3,7-dHTs) are highly oxygenated troponoids that have been identified as lead compounds for several human diseases. To date, structure-function studies on these molecules have been limited due to a scarcity of synthetic methods for their preparation. New synthetic strategies towards structurally novel 3,7-dHTs would be valuable in further studying their therapeutic potential. Here we describe the successful adaptation of a [5 + 2] oxidopyrilium cycloaddition/ring-opening for 3,7-dHT synthesis, which we apply in the synthesis of a plausible biosynthetic intermediate to the natural products puberulic and puberulonic acid. We have also tested these new compounds in several biological assays related to human immunodeficiency virus (HIV), hepatitis B virus (HBV) and herpes simplex virus (HSV) in order to gain insight into structure-functional analysis related to antiviral troponoid development.

Nocturnal partial seizures and arousals/awakenings from sleep: an ambulatory EEG study.

The architecture of nocturnal sleep in twenty subjects (9 males, 11 females, mean age 27 years) affected by partial cryptogenic epilepsy was investigated by means of ambulatory EEG (A-EEG) recording performed at home. The study aimed in particular to ascertain the immediate effects of nocturnal partial epileptic seizures on sleep stability and continuity. Data for a total of 49 recorded seizures indicate that 72% of the partial seizures which occurred during sleep were followed by arousal and awakening, and that sleep interruption lasted significantly longer when the seizure occurred between 4 and 7 a.m.

Poor sleep in adolescents: a study of 869 17-year-old Italian secondary school students.

Subjective sleep quality and its related factors were investigated in 869 (530 F, 339 M) 17-year-old adolescents, who were selected from the pupils of state-run secondary schools in the city of Pavia in the north west of Italy. The study was conducted cross sectionally, and it consisted of a questionnaire based survey. One hundred and forty-two subjects (16.5% of the whole sample, 19% of the females and 11.7% of the males) met the criteria chosen for definition as poor sleepers (namely, a complaint of 'non restorative nocturnal sleep', 'often' or 'always' over the previous 12 mo). A significant association was found between chronic poor sleep and (1) gender (female) (2) emotional factors, such as worries, anxiety and depression (3) poor sleep hygiene (4) arousal related parasomnia. Only 4% of poor sleepers took sleep promoting drugs (including benzodiazepines, homeopathic products and other medications), generally without seeking medical advice.

Eegraphic and behavioural effects of ondansetron, a 5HT3 antagonist, in rabbits.

1. EEGraphic and behavioural effects of ondansetron, a 5HT3 antagonist, have been studied in the rabbit. Subsequently we tested the neurophysiological and behavioural interactions between ondansetron and L-5-HTP induced serotonergic syndrome. 2. The drug produced a dose-dependent (0.001, 0.01, 0.1 mg/kg i.v.) increase in the cortical power density spectrum, particularly in the range of the lowest frequencies bands. This effect is expression of cortical synchronization. 3. The lowest and mild dose, but not the highest, failed to produce behavioural sedation and to inhibit the arousal induced by vibroacustical stimulation. 4. L-5-HTP (10 mg/kg i.v.) administration generated a typical EEGraphic-behavioural pattern characterized by a decrease of cortical power spectrum density and stereotyped movements. The EEGraphic effects were significantly suppressed by administration of mild and higher doses of ondansetron, while the behavioural effects were inhibited by all doses tested. 5. It is concluded that ondansetron acts with considerably efficacy on central nervous system. The administration of low and mild doses shows a singular dissociation between EEGraphic and behavioural actions. The inhibition of the L-5-HTP behavioural syndrome by ondansetron suggests that this drug acts on behaviour only when there is an altered physiological pattern.

[Electroencephalographic effects of a new triazolobenzodiazepine (Adinazolam) in the rabbit]. / Effetti elettroencefalografici di una nuova triazolobenzodiazepina (Adinazolam) nel coniglio.

In this study we investigated the central effects of adinazolam, a triazolobenzodiazepine, by means of neurophysiological techniques (electroencephalogram, EEG, and quantified analysis of EEG, QEEG). The drug has been administered at the doses of 0.1-1-10 mg/kg i.v. The evaluation of the data obtained by QEEG has demonstrated that this substance acts on the central nervous system. Particularly we observed that the drug at the middle and high doses caused an increase of the "slow waves sleep" EEG pattern. This preclinical study has shown that adinazolam possesses a neuropharmacological profile similar to that of atypical antidepressive and/or anxiolytic drugs.

[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.