The antiepileptic effect of low-dose amino-phosphono-valeric acid (APV) is not enhanced by phosphatidylserine association.

We investigated the effects of the NMDA antagonist amino-phosphono-valeric acid (APV), alone or in combination with phosphatidylserine (PS) in the penicillin model of epilepsy. After penicillin injection, rats were treated i.p. with either APV alone (5 mg/Kg) or APV (5 mg/Kg) + PS (740 mg/Kg). EEG epileptic activity decreased significantly in the group treated with APV alone, even at the very low dose used. This effect was not further enhanced by PS, suggesting that the previously reported effects of PS on GABA activity may be related to a specific interaction between these compounds.

Ischemic stroke and atrial fibrillation. A clinical study.

In view of the higher prevalence of severe ischemic stroke among patients with atrial fibrillation (AF) and of the recently reported higher frequency of stroke with AF in females, 516 consecutive patients with ischemic stroke, of whom 93 had AF, were retrospectively evaluated. The main anamnestic, clinical and laboratory features of the AF and non-AF groups were statistically compared and the features of the AF group were statistically evaluated according to gender and age. Our results confirm the greater severity of stroke in AF patients than in non-AF patients and the higher frequency of stroke with AF in female patients. Moreover, a significantly higher frequency of stroke with AF was found in the male 60-69 and the female 80-89 age groups than in the other age groups. Relevant risk factors in females aged 80-89 were hypertension and left ventricular hypertrophy (LVH), while diabetes, alcohol, smoking and LVH prevailed among 60-69 year old males.

Electric shock convulsions in the rabbit and brain cortex GABAA receptor function.

The effect of electric shock convulsions (ESC) on the function of brain cortex GABAA receptors has been studied in the rabbit. Three single electroconvulsive shocks (ECS) were given at intervals of 48 hours and the brain cortex was sampled 36 hours after the last shock. The dose-response curve was determined for GABA-stimulated 36Cl-accumulation into brain cortex microsacs. The parameters of the curve (maximal accumulation rate, Ka and Hill coefficient, n) were constant when determined in two different series of experiences. Animals handled in the same way as the animals from the electric shock group but which did not receive the ECSs (sham ECS group) showed similar maximal accumulation rate and Ka. However, the average n coefficient was significantly higher in the electric shock group. Naive animals, taken from their cages just before the sacrifice, showed dose-response curves which varied from one experimental series to another. This last result (confirming previous observations) shows modifications and inconsistencies in the evaluation of GABAA receptor function in stressed handling-naive animals.

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.

Accumulation of labeled gamma-aminobutyric acid into rat brain and brain synaptosomes after i.p. injection.

The accumulation of labeled GABA into brain and brain nerve endings was studied in the adult rat after i.p. injection of large doses of neurotransmitter (740 mg/Kg). In the first 5-30 minutes after the injection the exogenous neurotransmitter reaches a stable plasma level of around 5 mM. The accumulation of radioactive GABA into the brain presents a latency of a few minutes from the time of the injection. Thereafter, the accumulation of the neurotransmitter is almost linear with time. Once in the brain tissue labeled GABA is in part broken down. The exogenous neurotransmitter is taken up in GABA-ergic nerve endings with a steep increase between 20 and 30 minutes after the injection. From a quantitative point of view, the data show that the brain accumulation of labeled GABA at 30 minutes post injection is minimal in the respect of the steady state average concentration of the endogenous neurotransmitter (0.014%). However, the amount of radioactive GABA which accumulates in the nerve endings, at the same post injection time, is around 7% of the endogenous neurotransmitter in that compartment. The data thus show a selective enrichment of exogenous systemic GABA in a physiologically important compartment of the brain.

The excitatory amino acid antagonist amino-phosphono-valeric acid (APV) provides protection against penicillin-induced epileptic activity in the rat.

The effects of intraperitoneal injection of 2-amino-5-phosphono-valeric acid (APV) on EEG-monitored penicillin-induced epileptic activity in rats were evaluated. A significant decrease in the frequency of spikes occurred with low APV dosages (10 and 20 mg/kg), while an almost complete disappearance of spike activity was observed at higher APV doses (40 and 160 mg/kg). Our data suggest that excitatory amino acids play a relevant role in penicillin-induced epileptic activity in rats.