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F Piccoli

Publications and source records attributed to F Piccoli.

At least 37 records · Page 2Linked to original sources
PubMed1999

Protective effect of the cochlear efferent system during noise exposure.

The aim of the present study was to confirm the hypothesis that the cochlear efferent system is involved in the mechanisms underlying the "toughening" effect at high frequencies. The toughening effect is defined as a progressive threshold shift reduction when repeated exposures to the same noise are applied. Vestibular neurectomy was performed through a posterior cranial fossa approach in six healthy pigmented guinea pigs, and it assured the interruption of both crossed and uncrossed olivocochlear bundles to one ear only, before their entrance in the internal auditory meatus. The animals were then implanted with permanent electrodes for the electrocochleographic findings. Ten days after the operation the animals were exposed to octave-band toughening noise, centered at 4 kHz, at 85-dB SPL, for 10 consecutive days, 6 hours on/18 hours off. The hearing threshold was registered before and at the end of each exposure session. The behavior of the hearing threshold in the operated ears was then compared to that of the controlateral, nonoperated ears. Complete recovery from TS in the control ear began after four days of exposure, whereas in the operated ear hearing loss increased to day 7 (55 dB), with only a partial reduction (45 dB) beyond ten days of exposure. The results of the present study clearly demonstrated that sectioning of the OCB in guinea pigs causes persistent hearing loss during noise-exposure conditioning, in comparison to the contralateral, nonoperated ear. Thus, one can assume that the lack of decrease of TS during intermittent noise exposure could be due to the loss of the protective effect of the efferent fibers, perhaps mediated by the lateral OC neurons that synapse beneath the IHCs.

Animals↗
PubMed1999

Vestibular neurectomy in the guinea-pig: a retrosigmoid approach.

The efferent cochlear system, composed of both ipsi- and contralateral bundles, runs along with the vestibular nerve and may serve as protection for the inner ear. Sectioning of the vestibular nerve could thus create an experimental model for further in-depth study of such a protective role. A personal surgical approach is described, involving a suboccipital (or retrosigmoid) route to the postero-medial aspect of the guinea-pig temporal bone, chosen because of its use for the induction of endolymphatic hydrops in the same species. The crucial step in this approach is the separation of the sigmoid sinus in its entirety, through an intra-dural access with a minimal removal/retraction of cerebellar tissue. This did not affect either the post-operative recovery of the animal or its hearing threshold level as assessed via auditory brainstem responses.

Animals↗
PubMed1998

Pregnenolone sulfate modulates NMDA receptors, inducing and potentiating acute excitotoxicity in isolated retina.

Pregnenolone sulfate (PS) acts as a positive allosteric modulator of N-methyl-D-aspartate (NMDA) receptor-mediated responses. In the retina, we previously observed that the synthesis of pregnenolone and PS increases after stimulation of NMDA receptors and blockade of the synthesis reduces retinal cell death. This study was carried out to explore in the isolated and intact retina the possible role of PS in NMDA-induced excitotoxicity. Lactate dehydrogenase (LDH) measurements and morphological analysis revealed that a 90-min exogenous application of PS at 0.1-500 microM concentrations potentiated NMDA-induced cell death and at 50-500 microM concentrations caused cytotoxicity. After 45 min, either NMDA or PS caused no significant LDH release; but their co-application resulted in a high degree of toxicity. In addition, we found that a mild NMDA insult developed into serious damage when even low PS concentrations (0.1-10 microM) were used. Toxicity-inducing and -potentiating effects were specific to PS modulatory action on NMDA receptors, in that they were blocked by 4-(3-phosphonopropyl)2-piperazinecarboxylic acid (CPP) and MK-801 but not by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and neither dehydroepiandrosterone sulfate nor pregnenolone caused LDH release. Prevention of degenerative signs was seen in retinae pretreated with 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), a Cl- channel blocker, thus indicating a Na+/Cl--dependent acute mode of excitotoxic cell death responsible for PS toxicity. The positive interaction between the neurosteroid and NMDA receptors was further proved by a PS dose-dependent increase in NMDA-induced stimulation of [3H] MK-801 binding to retinal membranes. The results suggest a crucial role of PS in retinal vulnerability and propose the toxicity-potentiating effects as an important key in linking NMDA-induced endogenous synthesis to acute excitotoxicity.

Animals↗
PubMed1998

Induction of neurosteroid synthesis by NMDA receptors in isolated rat retina: a potential early event in excitotoxicity.

Here we investigated the possible regulation of neurosteroidogenesis by N-methyl-D-aspartic acid (NMDA) receptor activation and addressed the hypothesis that neurosteroid synthesis may be involved in acute excitotoxicity. In the isolated retina, exposure to NMDA modified pregnenolone and pregnenolone sulphate formation. This effect was dose and time dependent, the synthesis being increased by relatively moderate NMDA doses (1-100 microM) within 30 min exposure and reduced to its control value by 60 min or by raising drug concentrations. NMDA-stimulated neurosteroid synthesis was blocked by (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-imine hydrogen maleate (MK-801) and 3(2-carboxypiperazine-4-yl)propyl-1-phosphonic acid (CPP), depended on extracellular calcium and reproduced by glutamate. Lactate dehydrogenase (LDH) release and morphological analysis revealed that retinal cell viability was not significantly affected after 30 min exposure to 50 microM NMDA, but severe cell damage occurred by 60 min. When the GABAA (gamma-aminobutyric acid) receptor agonist muscimol (1-1000 microM), known to activate retinal neurosteroidogenesis, was added together with NMDA, no additional increase in neurosteroid synthesis was observed, and NMDA-induced LDH release remained unchanged. However, exposure to a high concentration of muscimol alone (500 microM) provoked a similar degree of toxicity to NMDA. By contrast, bicuculline abolished the increase in neurosteroidogenesis and LDH release. Similarly, pretreatment with R (+)-p-aminoglutethimide (AMG), an inhibitor of cholesterol side-chain cleavage cytochrome P450, attenuated acute retinal cell damage. The inhibitory nature of AMG on NMDA-stimulated neurosteroidogenesis was confirmed in the observation that drug treatment reduced pregnenolone content and did not affect the bindings of [3H] MK-801 and [3H] muscimol. The results demonstrate that NMDA receptors regulate neurosteroidogenesis through a transneuronal mechanism, which implies GABAA receptor activation. The early NMDA-mediated stimulation of neurosteroid synthesis seems to play a critical role in acute excitotoxicity; consequently, its inhibition is likely to delay neuronal cell death.

Animals↗
PubMed1997

Dietary consumption of Lathyrus sativus seeds induces behavioral changes in the rat.

Neurolathyrism is a degenerative disorder due to an excessive consumption of Lathyrus sativus (LS) seeds, which contain the neurotoxic amino acid beta-N-oxalylamino-L-alanine. In this study, a population of Wistar rats was fed a diet with LS seeds up to 8 months. Two control groups were chosen, one receiving standard food and the other Cicer arietinum seeds (a nontoxic legume). At the end of the dietary period, the groups previously fed the seeds were switched to standard food for 1 month (wash-out). All animals were submitted to a neurological examination and observed in an open-field situation before, during the diet (at 4 and 8 months), and finally after wash-out. Neither LS-fed rats nor controls ever showed neurological deficits. By contrast, in an open-field the activity was significantly increased in the LS-eating rats at both the 4th and 8th month. The effect was indeed reversible, since it disappeared after the wash-out. It is suggested that the enhanced open-field activity seen in the LS group might indicate a reversible excitable status. However, there is no evidence at present that the behavioral changes described represent a marker of neurodegeneration in this animal species.

Animals↗
PubMed1995

gamma-Aminobutyric acid type A/benzodiazepine receptors regulate rat retina neurosteroidogenesis.

It has been previously shown that retinal ganglion cells have the ability to synthesize steroids including neuroactive steroids such as pregnenolone sulfate. Since ganglion cells possess GABAA/benzodiazepine (BZ) receptors and neurosteroids modulate retinal GABAA receptor function, we investigated the role of these receptors in isolated rat retina neurosteroidogenesis. Ligands for central-type BZ receptors stimulated retinal pregnenolone synthesis. Clonazepam was the most potent ligand examined acting at nanomolar concentrations. Moreover, the effective steroidogenesis stimulatory dose (ED50) for these ligands and the Ki to inhibit [3H]flunitrazepam binding showed a coefficient of correlation of r = 0.87, suggesting the involvement of the central-type BZ receptors in this event. Ro 5-4864, which preferentially binds to peripheral-type BZ receptors, was less efficacious and potent whereas PK 11195 did not affect the basal pregnenolone formation and did not antagonize the Ro 5-4864 stimulated steroid synthesis. The GABAergic agonist muscimol, stimulated neurosteroid synthesis and this effect was reversed by the GABAergic antagonists bicuculline and picrotoxinin. In addition, these antagonists decreased basal pregnenolone formation, suggesting a tonic GABAergic control of the steroidogenic pathway, and reduced clonazepam-stimulated steroidogenesis. These results, together with the reported ability of neurosteroids to modulate GABAA receptor function, suggest a novel regulatory mechanism to control the inhibitory transmission.

Animals↗
PubMed1995

[Description of a case of squamous cell carcinoma of the renal pelvis].

A case of squamous cell carcinoma of renal pelvis is reported. A 73-year-old Caucasian male complained of macrohematuria. The echography and Computer Tomography scan of the abdomen and pelvis revealed a large tumor mass in the right kidney associated with lymphadenopathy. A nephrectomy of the right kidney and lymphadenectomy were performed. The isotologic examination revealed a squamous carcinoma of the renal pelvis involving the renal parenchyma and extending to the perirenal fat. The regional lymph nodes were also involved. Neoplastic invasion of inferior vena cava was found. Squamous carcinoma in situ and squamous metaplasia were noted in the urothelium adjacent to the tumor. Three months later an echography revealed a local recurrence of the disease. The patient underwent adjuvant chemotherapy. The aggressive course of the disease is in agreement with the poor prognosis of squamous carcinomas of the renal pelvis as previously reported in the literature.

Aged↗
PubMed1995

Dopaminergic agonists in the treatment of Parkinson's disease: a review.

Dopaminergic agonists represent an important class of drugs in Parkinson's Disease, useful: a) in delaying the beginning of L-dopa therapy; b) in supporting it, reducing its dosage and widen the therapeutic window; c) moreover, as the disease advances, in trying to treat motor fluctuations. Authors describe briefly the problems caused by long term L-dopa therapy, and analyze, separately, the characteristics of the most important dopaminergic agonists currently utilized in the treatment of PD.

Antiparkinson Agents↗
PubMed1994

Neurosteroidogenesis in rat retinas.

Neurosteroids (steroids synthesized in the CNS) function by modulating neurotransmission. To establish an experimental model for investigation of neurosteroid synthesis and regulation, independent of blood-borne steroids, we examined the steroidogenic activity of isolated rat retinas. We identified progesterone, pregnenolone, dehydroepiandrosterone, desoxycorticosterone, 3 alpha,5 alpha-tetrahydrodesoxycorticosterone, 3 alpha-hydroxy-5 alpha-dihydroprogesterone, 17-hydroxyprogesterone, and 17-hydroxypregnenolone together with their esterified forms. As pregnenolone is the precursor of all steroids, its formation was studied in detail as an index of a steroid-synthesizing tissue. Pregnenolone was identified further by gas chromatography coupled to mass spectrometry, and its in vitro synthesis was inhibited by lovastatin, an inhibitor of mevalonolactone and cholesterol biosynthesis. We then examined pregnenolone synthesis in the presence of mevalonolactone as a precursor of sterol formation together with lovastatin, which reduces endogenous mevalonolactone synthesis, as well as with inhibitors of pregnenolone metabolism. The incorporation of mevalonolactone into pregnenolone and its sulfate ester was time- and concentration-dependent and blocked by aminoglutethimide, a competitive inhibitor of cytochrome P450 side-chain cleavage (P450scc) enzyme. Immunocytochemical studies with a specific antibody to P450scc revealed a primary localization of the enzyme at the retinal ganglion cell layer. A less pronounced immunostaining was also seen at cells of the inner nuclear layer. Compounds known to stimulate cyclic AMP content also stimulated pregnenolone formation by rat retinas. These results demonstrate that rat retinas synthesize steroids and, for the first time, they reveal the steroidogenic ability of neuronal cells. We propose rat retinas as an in vitro model system to study neurosteroidogenesis in the CNS.

Aminoglutethimide↗
PubMed1993

Effect of beta-N-oxalylamino-L-alanine on cerebellar cGMP level in vivo.

Beta-N-oxalylamino-L-alanine (BOAA), a non-protein amino acid present in the seeds of Lathyrus Sativus (LS), is one of several neuroactive glutamate analogs reported to stimulate excitatory receptors and, in high concentrations, cause neuronal degeneration. In the present study, the in vivo acute effects of synthetic BOAA and LS seed extract were investigated on rat cerebellar cyclic GMP following intraperitoneal (10-100 mg/kg) or oral (100 mg/kg) administration of subconvulsive doses of toxin. Furthermore, the BOAA content in LS seeds and in the cerebellum of injected rats was determined by high performance liquid chromatograph analysis. A dose- and time-dependent increase of cerebellar cyclic guanosine monophosphate (cGMP) level was observed after intraperitoneal administration of synthetic BOAA or LS extract. The neurotoxin evoked a maximum stimulation 90 min after injection within the dose range of 50-75 mg/kg, elevating cGMP from basal levels of 5.3 +/- 0.5 pmol/mg protein to 15 +/- 1.3 pmol/mg protein. Similarly, the oral intake of LS-extracted neurotoxin resulted in the elevation of cGMP content. Kynurenic acid (300 mg/kg i.p.), a non specific excitatory amino acid antagonist, was effective in blocking LS BOAA-elicited cGMP enhancement. The data suggest that in the cerebellum acute administration of low concentrations of BOAA exert in vivo activation of glutamate receptors involved in the regulation of cGMP level.

Administration, Oral↗
PubMed1993

Electroretinographic response in WAG/Rij rats after low-intensity cyclic light exposure.

In order to investigate the combined influence of age and light, the b-wave and oscillatory potentials (OPs) of the electroretinogram (ERG) were recorded in 1.5-, 7- and 12-month-old WAG/Rij rats, reared under homogenous low-intensity cyclic light exposure. Wistar albino rats of the same ages, reared under the same conditions, served as controls. The b-wave amplitude decreased, and its implicit time increased in the older age groups significantly more in WAG/Rij than in Wistar rats. Statistical analysis indicated that the b-wave amplitude is a more suitable parameter than implicit time in differentiating the ERG variations of one rat strain from the other. The added amplitude of the OPs also decreased in older age groups, but differently from the b wave. This occurred in WAG/Rij rats already at 1.5 months of age.

Aging↗
PubMed1992

Myasthenia gravis associated with Charcot-Marie-Tooth neuropathy: report of a case.

We report the case of a 24 year old woman who developed myasthenia gravis in the course of a mild form of Charcot-Marie-Tooth neuropathy. We describe the clinical manifestations together with the neurophysiological, pathological, serological findings and response to therapy and discuss the unusual association in the light of the relevant literature.

Adult↗
PubMed1992

Brainstem auditory evoked potentials in patients with mitochondrial encephalomyopathy.

Brainstem auditory evoked potentials (BAEPs) were evaluated in three patients with mitochondrial encephalomyopathy belonging to the same family. This study showed marked alterations of BAEPs in all patients: reduction of wave amplitude, poor repeatability of responses in test-retest and abnormalities in wave form and latency. The neuroradiological examinations (CT-scan, MRI) did not show significant structural brain abnormalities. Abnormal BAEPs in our patients may be related to central metabolic disorder rather than hearing loss.

Adult↗
PubMed1990

[Endoscopic resolutions of volvulus of the sigmoid colon].

The flexible colonoscope has brought considerable advantages to the diagnosis and nonsurgical treatment of volvulus. In the case of repeated recurrences that make surgery vital because of the onset of signs of vascular trouble on the twisted ansa, preoperative resolution permits correction of hydroelectrolytic imbalances and the preparation of the colon with the possibility of operating with no need for protective colostomy. It also allows resolution of the acute situation in the presence of contraindications to intervention.

Adult↗
PubMed1990

Binding of flunitrazepam to differentiating neurons cultured in a chemically defined, hormone-supplemented medium.

[3H]Flunitrazepam (FNZ) binding to cortical neurons from fetal rat brain was investigated in vitro. The use of a synthetic medium specific for neurons made it possible to plot a developmental curve of 3H-FNZ binding in an almost pure neuronal culture. Detectable specific binding was present in vitro at time 0 (that is, the 16th gestational day). A progressive increase of binding, due to an increment in the number of recognition sites, was observed on the subsequent days. The affinity of the specific binding sites to 3H-FNZ was enhanced by the addition of exogenous GABA, whereas the density was not affected.

Animals↗