Quantitative characterisation of the ring normal modes. Pyridine as a study case.

In the present work, the vibrational normal modes (NM) of pyridine were revisited. Quantum Chemical calculations were performed to help understand the true nature of some ring related vibrational normal modes (RNM) and how they may be correlated with the electronic structure on the ring. The 27 vibrational normal modes were decomposed into the molecular internal coordinates, and the interest was focused on 7 of them, involving the in-plane ring motion. The electronic structure was analysed through frontier Molecular Orbitals (MO), maps of Molecular Electrostatic Potential surfaces (MEPs) and Natural Bond Orbital (NBO) analysis in a dynamic manner, wherein, each vibration was scanned. The present investigation is aimed to provide the Reader with a quantitative characterisation of the RNMs of pyridine.

An ultrafast spectroscopic and quantum mechanical investigation of multiple emissions in push-pull pyridinium derivatives bearing different electron donors.

A joint experimental and theoretical approach, involving state-of-the-art femtosecond fluorescence up-conversion measurements and quantum mechanical computations including vibronic effects, was employed to get a deep insight into the excited state dynamics of two cationic dipolar chromophores (Donor-π-Acceptor(+)) where the electron deficient portion is a N-methyl pyridinium and the electron donor a trimethoxyphenyl or a pyrene, respectively. The ultrafast spectroscopic investigation, and the time resolved area normalised emission spectra in particular, revealed a peculiar multiple emissive behaviour and allowed the distinct emitting states to be remarkably distinguished from solvation dynamics, occurring in water in a similar timescale. The two and three emissions experimentally detected for the trimethoxyphenyl and pyrene derivatives, respectively, were associated with specific local emissive minima in the potential energy surface of S1 on the ground of quantum-mechanical calculations. A low polar and planar Locally Excited (LE) state together with a highly polar and Twisted Intramolecular Charge Transfer (TICT) state is identified to be responsible for the dual emission of the trimethoxyphenyl compound. Interestingly, the more complex photobehaviour of the pyrenyl derivative was explained considering the contribution to the fluorescence coming not only from the LE and TICT states but also from a nearly Planar Intramolecular Charge Transfer (PICT) state, with both the TICT and the PICT generated from LE by progressive torsion around the quasi-single bond between the methylpyridinium and the ethene bridge. These findings point to an interconversion between rotamers for the pyrene compound taking place in its excited state against the Non-equilibrated Excited Rotamers (NEER) principle.

Extra-linguistic influences on sentence comprehension in Italian-speaking children with and without specific language impairment.

BACKGROUND: Many children with specific language impairment (SLI) in sentence comprehension. These deficits are usually attributed to limitations in the children's understanding of syntax or the lexical items contained in the sentences. This study examines the role that extra-linguistic factors can play in these children's sentence comprehension. AIMS: Extra-linguistic demands on sentence comprehension are manipulated directly by varying the nature of the materials used. METHODS & PROCEDURES: Forty-five Italian-speaking children participated: 15 with SLI (mean age = 4;5), 15 typically developing children matched for age (TD-A, mean age = 4;5), and 15 younger typically developing children matched according to language comprehension test scores (TD-Y, mean age = 3;9). The children responded to sentence comprehension items that varied in their length and/or the number and type of foils that competed with the target picture. OUTCOMES & RESULTS: The TD-A children were more accurate than the TD-Y children and the children with SLI, but, for all groups, accuracy declined when task demands increased. In particular, sentences containing superfluous adjectives (e.g., Il topo bello copre l'uccello allegro, 'The nice mouse covers the happy bird' where all depicted mice were nice and all birds were happy) yielded higher scores than similar sentences in which each adjective had to be associated with the proper character (e.g., Il cane giallo lava il maiale bianco, 'The yellow dog washes the white pig', where foils included a yellow dog washing a pink pig, and a brown dog washing a white pig). Many errors reflected recency effects, probably influenced by the fact that adjectives modifying the object appear at the end of the sentence in Italian. CONCLUSIONS & IMPLICATIONS: Differences between conditions were observed even when lexical content, syntactic structure and sentence length were controlled. This finding suggests the need for great care when assessing children's comprehension of sentences. The same syntactic structure and lexical content can vary in difficulty depending on the number and types of foils used in combination with the target picture.

[First trimester screening for Down syndrome: five years prospective experience]. / Dépistage combiné de la trisomie 21 au premier trimestre : à propos de cinq ans d'expérience prospective multicentrique.

First trimester screening for Down syndrome is yet to become the first intention strategy in France. This screening program at 11-14 weeks of gestation using maternal age, fetal nuchal translucency, maternal serum free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A has already been validated for a long time by many international studies. It seems to improve detection rate and decrease false positive rates. We report here five years prospective experience.

Evaluation of the mechanisms by which gamma-amino-butyric acid in association with phosphatidylserine exerts an antiepileptic effect in the rat.

The i.p. injection in rats of GABA (740 mg/Kg) after sonication with an equal amount of phosphatidylserine (PS) has an antiepileptic effect. The injection of plain GABA has no such an effect. Blood, brain and synaptosomal accumulation of exogenous labeled GABA under the two circumstances are evaluated. In the case of GABA/PS injection there is a higher passage of the exogenous labeled neurotransmitter into the blood and brain nerve endings (synaptosomes). A higher synaptosomal accumulation of the exogenous labeled neurotransmitter is found even when GABA and PS are injected separately. Since these accumulation increases occur at a time when there is the antiepileptic effect, they seem relevant to it. Our interpretation of the chain of the events resulting in the antiepileptic action is that the phospholipid facilitates from the beginning the first passage of the exogenous neurotransmitter form the peritoneum to the blood. Then a higher passage to the brain tissue and eventually to the GABA-ergic nerve endings ensues. The brisker accumulation of the exogenous neurotransmitter in the nerve endings could be at the basis of a more efficient GABA-ergic inhibitory control in the brain.

Preliminary note on the effect of denzimol in partial epilepsy.

The antiepileptic activity of the imidazole derivative denzimol has been evaluated in 10 patients with poorly controlled partial epilepsy by adding on the drug to the current therapy, in an open preliminary trial. A sustained drop in seizure frequency greater than 50% occurred in 5 patients. Although denzimol increased blood concentrations of carbamazepine, correlation analysis indicated that the improvement was more likely due to intrinsic properties of denzimol. No severe side effects were reported, although several patients experienced nausea and vomiting, which caused 2 patients to drop out.

Phosphatidylserine increases in vivo the synaptosomal uptake of exogenous GABA in rats.

A sonicated liposome suspension of gamma-aminobutyric acid (GABA) and phosphatidylserine (liposome-entrapped GABA), intraperitoneally administered in rats, inhibited EEG epileptic activity induced by penicillin, whereas GABA did not. A significant increase (20.4%) in brain radioactivity accumulation occurred at 5 min after i.p. administration of [14C]GABA associated with phosphatidylserine in comparison with the administration of [14C]GABA; such an increase persisted after 20 min. However, the accumulation of radioactivity into brain synaptosomes demonstrated a 24.1% increase at 5 min and subsequently showed a 43.3% increase at 20 min after injection of liposome-entrapped GABA. The above findings suggest that phosphatidylserine stimulates exogenous GABA uptake into brain GABAergic nerve terminals.

Blood levels of progabide and its active metabolite in epileptic patients: relationships to the therapeutic outcome.

To assess the relationships between the efficacy and blood levels of progabide (PGB) and its active acidic metabolite (PGA) in epileptics, observations were carried out on 89 adult patients with epilepsy of different types and severity in two groups at Paris and Genoa. The Paris group received progabide in addition to other antiepileptic drugs for 6 to 12 months, whereas the Genoa group received a polytherapy for the first two months then a monotherapy with progabide alone for up to 22 months. Blood levels from monthly or bimonthly samples were significantly higher in both surveys when there was a satisfactory therapeutic response and levels were also higher in those receiving monotherapy suggesting a synergism among antiepileptic drugs. It is concluded that therapeutic drug monitoring of PGB and PGA blood concentrations may be a useful technique in optimizing progabide treatment in epileptic patients.

Preliminary observations on the activity of progabide, administered as monotherapy in complex partial seizures.

Progabide (PGB), a gamma-amino-butyric acid receptor agonist, was administered, according to an open-label long-term design, to 40 adult patients suffering from complex partial seizures, with or without secondary generalization, whose response to carbamazepine (CBZ) monotherapy was unsatisfactory. A reference-baseline period of two months with carbamazepine monotherapy was followed by a two-month "add-on" period where increasing doses of progabide were added without modifying the CBZ regimen; then CBZ was withdrawn over 15-60 days and patients were followed up to 12 months' progabide treatment. Twenty-seven patients completed the trial but 12 of them had to be returned to CBZ + PGB bitherapy due to an increase of seizures following CBZ withdrawal. A definite therapeutic effect could be observed in nine patients on PGB monotherapy and in six patients on CBZ + PGB bitherapy. Side-effects of clinical relevance occurred in three cases and were represented by remarkable anxiety in two patients and a rise in serum glutamic oxalo-acetic acid and pyruvic transaminases with clinical symptoms of liver dysfunction in one, with rapid recovery following progabide discontinuation. In conclusion, progabide was effective against complex partial seizures in about 40% of patients not responding satisfactorily to available antiepileptic drugs. Although the withdrawal of previous antiepileptic drugs was not possible in all patients, progabide monotherapy was sometimes more effective than CBZ monotherapy, and several patients in whom bitherapy had to be restored benefited from the association of progabide.

Carbamazepine and cardiac conduction disturbances.

Carbamazepine-induced cardiac conduction disturbance is reported in 2 patients suffering from epilepsy. The cardiac defects disappeared in both patients after carbamazepine was discontinued, and reappeared in 1 patient after treatment was resumed.

Preliminary evaluation of the effect of GABA and phosphatidylserine in epileptic patients.

The effect of the combined administration of gamma-aminobutyric acid (GABA) and phosphatidylserine was evaluated in a pilot study of 42 patients with drug-resistant epilepsy. The group included patients with complex partial seizures, simple partial seizures and absence seizures. Patients with complex partial seizures and simple partial seizures showed no significant improvement; on the other hand, there was a remarkable decrease in absence seizures, linearly related to the dose of GABA and phosphatidylserine. Side effects occurred in 9 patients and were usually mild.

Parenteral penicillin model of epilepsy in the rat: a reappraisal.

A parenteral penicillin model of epilepsy in the rat was investigated with the aim of evaluating its reliability. Behavioral and EEG patterns were strongly variable in a group of 100 rats injected with 1,000,000 IU/kg of penicillin i.p. Gross counts of spikes were Fourier transformed and grouped into two time windows in 24 out of the 100 rats. Analysis of variance applied to compare the two time windows showed a sufficient suitability of the phenomenon for antiepileptic drug testing purposes. Five subsequent injections of penicillin performed in 8 rats showed that a spontaneous decrease of the response takes place, preventing a crossover design in pharmacological analyses. Evans Blue studies demonstrated that there was not a breakdown of the blood-brain barrier; this model can be used for testing anticonvulsants unable to penetrate the blood-brain barrier.

Liposome-entrapped gamma-aminobutyric acid inhibits isoniazid-induced epileptogenic activity in rats.

Sprague-Dawley rats with interictal and ictal spike activity induced by intraperitoneally injected isoniazid (INH) were treated, 5 min before or 30 min later, with liposome-entrapped gamma-aminobutyric acid (GABA) (LEG) or GABA or phosphatidylserine. Crossover injections were given in random sequence and INH alone ws also injected in every animal as a control. LEG inhibited either seizures or interictal spikes in both groups. No decrease of epileptogenic activity was seen after GABA or phosphatidylserine treatment alone. It is suggested that LEG could contribute to the reconstitution of the GABA pool decreased by INH.

GABA and phospholipids in penicillin-induced seizures.

The effect of a suspension of GABA and phosphatidylserine (PS), phosphatidylcholine, or phosphatidylethanolamine was studied on penicillin-induced epileptic activity in rats. GABA-PS significantly reduced the number of spikes, in comparison with either the other phospholipid compounds or normal saline. No effect was observed after GABA or PS administration alone. We suggest that the different effects probably depend on extracellular and intracellular factors.

Polygraphic-television recording in a case of syncope.

In a case of loss of consciousness presenting diagnostic difficulties, the syncopal nature was determined only with the help of combined polygraphy and closed circuit television recording.

[Retrospective study on side effects in 410 patients in antiepileptic therapy. Proposal for new biochemical screening]. / Studio retrospettivo sugli effetti collaterali di 410 pazienti in terapia antiepilettica. Proposta di un nuovo screening bioumorale.

The authors evaluated hematological side effects in 410 epileptic patients under chronic therapy. The aim of the study was to find out the most suitable parametres for preliminary screening. Values outside the normal range were seen in patients treated with multiple drug therapy and in patients receiving antiepileptic drugs from 3 years at least. The following tests were the most frequently influenced: GOT, GPT, alcaline phosphatase, protrombin time, fibrinogen.

Parenteral penicillin epilepsy: tolerance to subsequent treatments.

We recorded spike activity induced by i.p. penicillin injections in eight rats, repeating the experiment five times per each rat, at 48-h intervals. Spike frequency was significantly reduced in all sessions subsequent to the first, without changes in penicillin blood concentrations. The penicillin model of epilepsy is therefore not advisable in studies on antiepileptic drugs with a crossover design.

Liposome-entrapped GABA modifies behavioral and electrographic changes of penicillin-induced epileptic activity.

We studied Sprague-Dawley rats with spike activity and myoclonus after intraperitoneal injections of penicillin. Twenty minutes after penicillin injection, one group received a random crossover treatment by intraperitoneal GABA (gamma-aminobutyric acid) or liposome-entrapped GABA (LEG) or phosphatidylserine alone. The other group received GABA, LEG, or phosphatidylserine followed 15 minutes later by the injection of penicillin. LEG decreased or prevented the epileptic activity, whereas no significant changes were seen with either GABA or phosphatidylserine given alone. LEG may enhance penetration of GABA across the blood-brain barrier because of the carrier action of the liposomes.

Mental impairment and intelligence g factor: a psychometric profile.

Correlation among psychometric tests in normal Ss (N = 102) was examined for g factor saturation. A psychometric profile employing a test battery was drawn for use with neuropsychiatric patients (N = 35) to study whether mental impairment is due to a destruction of the general intelligence or of some specific intellectual function. Specific intellectual functions seem to have been involved, albeit at different degrees, Attentive abilities were the most impaired, abstract thinking the least. A methodological approach is proposed for further studies on mental impairment in neurological disorders.