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Biomedical subjects

P Mainardi

Publications and source records attributed to P Mainardi.

At least 19 recordsLinked to original sources
PubMed2006

Successful treatment of epilepsy with serotonin reuptake inhibitors: proposed mechanism.

The widely used antidepressants Specific Serotonin Reuptake Inhibitors (SSRI) have been tried with success as anticonvulsants in cases of nonsymptomatic epilepsy. This attempt was performed on the basis of experimental data suggesting the involvement of impairments of the serotonin system in the genesis of epilepsy. This overview summarizes the clinical data and presents biochemical and neurochemical evidences suggesting the mechanism of the therapeutic effects of SSRI in nonsymptomatic epilepsy. In particular, studies on blood-borne neutral amino acids and platelet serotonin transporter (SERT) in epileptics suggest: (a) That a decreased brain availability of tryptophan may be related to some types of epilepsy. (b) That reduction of the density of SERT may be a homeostatic reaction in the brain following epileptic seizures.

Adolescent↗
PubMed2001

Regulation of the expression of low affinity GABAA receptors in rat cerebellar granule cells.

GABAA receptors of cerebellar granule cells obtained from neonatal rats and kept in culture were studied by labelled muscimol binding. The data show that, according to the maturational state of those cells in vivo, one or two binding components appear. The low affinity component seems to be the one appearing later. The expression of this component seems to be regulated by protein tyrosine phosphorylation. In fact, its expression is down regulated by the protein tyrosine kinase (PTK) inhibitor, genistein. Viceversa, its expression is upregulated by insulin like growth factor I (IGF-I), most probably via PTK activation. A possible interpretation of the data is that in vivo IGF-I is one of the endogenous messages leading to the expression of this component during development. Another endogenous factor involved may be GABA itself. Low affinity GABAA receptors appear to be the ones involved in inhibitory synaptic transmission at glomeruli. Whereas the high affinity ones probably correspond to extrasynaptic GABAA receptors mediating the tonic form of inhibition in cerebellar granules.

Animals↗
PubMed1997

Effect of nitric oxide donors on GABA uptake by rat brain synaptosomes.

The effect of nitric oxide donors and L-arginine on the uptake of GABA was studied in synaptosomes purified from rat brain. The neurotransmitter uptake was significantly reduced by S-nitrosoacetylpenicillamine and by sodium nitroprusside, although in this case to a lesser extent. A slight inhibitory effect was found preincubating rat brain synaptosomes with 1 mM L-arginine as well. The S-nitrosoacetylpenicillamine effect gradually disappeared with decomposition of the substance by exposure to light. The nitric oxide effect appears to be mainly due to a decrease in the V for synaptosomal GABA uptake and seems to be related to a partial collapse of nerve endings ionic gradients. Functionally, it could result over time in a reduced availability of GABA at the synapses involved.

Animals↗
PubMed1997

Blunt pancreatic trauma. Role of CT.

PURPOSE: To define the evolution patterns of blunt pancreatic trauma, and to point out the CT features most significant for the diagnosis. MATERIAL AND METHODS: Ten cases of pancreatic trauma, observed over a period of about 10 years, were analyzed in retrospect. The cases were divided into 3 groups according to the time that had elapsed between trauma and first CT: early phase (within 72 h: n=3/10); late phase (after 10 days: n=3/10); and following pancreatic drainage (n=4/10). RESULTS: In the early phase, one case showed a blood collection surrounding the pancreatic head and duodenum, and displacing the mesenteric vessels to the left. In the 2 other cases it was possible to demonstrate a tear in the pancreas at the neck, perpendicular to the main pancreatic axis. In the late phase in all 3 cases, one cystic lesion was present at the site of the tear, either surrounding the gland or embedded - more or less deeply - within the parenchyma. One of the lesions subsided spontaneously; the 2 others required surgery. In the postoperative phase, an external fistula was demonstrated in 2 cases following percutaneous drainage of pancreatic cysts; the fistula was fed by a cystic lesion in the pancreatic neck. In the 2 other cases a pseudocyst developed. CONCLUSION: Early demonstration of a parenchymal tear was difficult. At a later stage the diagnosis was easier owing to the demonstration of cystic lesions within the parenchyma at the site of the tear. The surgical drainage of this lesion does not usually lead to healing since an external fistula or a pseudocyst may develop.

Adult↗
PubMed1996

Intraductal mucin-producing tumors of the pancreas: imaging findings.

PURPOSE: To evaluate the radiologic characteristics of intraductal mucin-producing tumors of the pancreas. MATERIALS AND METHODS: Sixteen patients with intraductal tumors underwent ultrasound (US); (n = 15), computed tomography (CT); (n = 16), endoscopic retrograde cholangiopancreatography (ERCP); (n = 12), and intraoperative pancreatography (n = 2). Findings were compared with those from surgery (n = 14) or biopsy (n = 2). RESULTS: Lesions were classified as either main duct type or branch duct type tumors. Main duct tumors were characterized at US and CT by either diffuse or segmental dilatation of the Wirsung duct. Pancreatography showed ductal dilatation and filling defects caused by mucin deposits. At US and CT, branch duct tumors, which were mainly located at the uncinate process, were seen as fluid-filled masses with central septa and the pancreatic duct was dilated. ERCP showed partial or complete opacification of the lesion. In four patients, endoscopy showed protrusion of the papilla into the duodenal lumen and mucin leaking from its dilated orifice. CONCLUSION: Imaging modalities, especially US and ERCP, enable early diagnosis of mucin-producing pancreatic tumors.

Adenocarcinoma, Mucinous↗
PubMed1995

Anticonvulsant effect of fluoxetine in humans.

We report an unblinded, open-label, add-on trial of fluoxetine, a selective serotonin reuptake inhibitor, in 17 patients with complex partial seizures with and without secondary generalization (mean follow-up duration, 14 +/- 1.1 months). Six patients showed complete disappearance of their daily seizures; in the others the seizure frequency was lowered by 30%. No patient reported side effects.

Adolescent↗
PubMed1993

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.

2-Amino-5-phosphonovalerate↗
PubMed1993

Antipyretic and platelet antiaggregating effects of nimesulide.

Nimesulide strongly inhibited ex vivo platelet aggregation in guinea-pigs after both single and repeated (once daily for 5 days) oral dosing, irrespective of the aggregating agent used (adenosine diphosphate, arachidonic acid or collagen). Its potency was consistently greater than that shown by either ticlopidine or acetylsalicylic acid. In both oral and rectal administration, nimesulide proved to be more active and longer lasting than paracetamol in inhibiting fever induced in rats injected subcutaneously with brewer's yeast.

Animals↗
PubMed1992

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.

Animals↗
PubMed1992

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.

Animals↗
PubMed1992

Components of basal and GABA activated 36Cl- influx in rat cerebral cortex microsacs.

The basal and GABA activated accumulation of labelled chloride in rat cerebral cortex microsacs has been studied as a function of incubation time. Basal accumulation has biphasic kinetics within 2 minutes of incubation with two components clearly visible. GABA activated stimulation has two phases as well, starting from (GABA) = 10(-5) M, one appearing within seconds of incubation range and the other one within tens of seconds. Both GABA-activated components are blocked by bicuculline methiodide (BMI). Practically no effect by 10(-3) M nipecotic acid was found on either the comparatively rapid or the slower phase. The two GABA activated components may correspond to two different populations of sealed vesicles with different receptor concentration per internal volume.

Animals↗
PubMed1990

Effect of phosphatidylserine on the basal and GABA-activated Cl- permeation across single nerve membranes from rabbit Deiters' neurons.

The permeation of labeled Cl- ions across single plasma membranes from Deiters' neurons has been studied in the presence of various concentrations of phosphatidylserine (PS) on their extracellular side. PS reduces significantly basal Cl- permeation only at 10(-5) M on the membrane exterior. No effect was found at other concentrations. GABA activable 36Cl- permeation is heavily reduced and almost abolished at 10(-11) - 10(-5) M phosphatidylserine. This exogenous phosphatidylserine effect is difficult to interpret in relation to the function of the endogenous phospholipid. However, it may be involved in the epileptogenic effect in vivo of exogenous phosphatidylserine administration to rats.

Animals↗
PubMed1990

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.

2-Amino-5-phosphonovalerate↗
PubMed1989

Histamine as a central modulator of rat intestinal transit.

Histamine (HA) injected i.c.v. to rats inhibited intestinal propulsion in linear relation to the log of the administered doses (in the range from 20-100 micrograms/rat). In the same dose range HA also induced a dose-related analgesic effect (tail-flick test). The dose of HA maximally active by the i.c.v. route (100 micrograms/rat) showed neither of these effects when injected i.v. or i.p. HA-induced intestinal inhibition and analgesia were antagonized competitively by i.c.v. mepyramine (10 micrograms/rat), an H1 receptor antagonist, whereas cimetidine (10 micrograms/rat), an H2 receptor antagonist, had no effect. Repeated i.c.v. injections of HA resulted in tachyphylaxis of both intestinal inhibition and analgesia. Pretreatment with i.c.v. naloxone (20 micrograms/rat) antagonized the antipropulsive effect of HA in a noncompetitive fashion, but did not affect its antinociceptive action. The relevance of the central histaminergic system in the modulation of gastrointestinal motility and its relationship with the opioid system are discussed.

Analgesia↗
PubMed1988

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.

Animals↗
PubMed1988

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.

Adolescent↗