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L Frattola

Publications and source records attributed to L Frattola.

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

Effect of recombinant human nerve growth factor on cisplatin neurotoxicity in rats.

In this study we evaluated the effect of recombinant human nerve growth factor (rhNGF) on cisplatin (CDDP)-induced sensory neuronopathy in an experimental paradigm in the rat. Young adult female Wistar rats were treated with CDDP (2 mg/kg ip twice weekly for nine times) alone or in combination with rhNGF (1 mg/kg sc on alternate days). The effect of CDDP +/- NGF treatment was evaluated with behavioral (tail-flick test) and neurophysiological (nerve conduction velocity in the tail) methods immediately after treatment and after a follow-up period of 6 weeks. Pathological and morphometrical examinations of the dorsal root ganglia (DRG) and sciatic and saphenous nerves were also performed. rhNGF treatment induced a significant reduction in the CDDP-induced decrease in nerve conduction velocity (P < 0.05), and this was associated with a significant protection against the decrease in somatic (P < 0.05), nuclear (P < 0.05), and nucleolar size (P < 0.01) caused by CDDP treatment. However, for each of the parameters examined the neuroprotection obtained with rhNGF treatment was not complete. At the follow-up examination no differences between the three groups were observed in tail-flick test and nerve conduction velocity. We conclude that rhNGF, administered according to the schedule used in this experiment, exerts a biologically significant neuroprotective effect against CDDP peripheral neurotoxicity.

Animals↗
PubMed1999

Reduced platelet glutamate uptake in Parkinson's disease.

Defects in mitochondrial enzymes have been found not only in substantia nigra, but also in platelets from Parkinson's Disease (PD) patients, suggesting a systemic impairment of energy metabolism. Since platelets present an energy-dependent glutamate uptake similar to that described in central nervous system, glutamate uptake was determined in platelets from 34PD patients and 21 age-related normal controls, as Na+-dependent [3H]glutamate influx; glutamate level was also analyzed by reverse-phase HPLC. A 50% reduction of glutamate uptake (p < 0.001) was observed in idiopathic PD patients, respect to controls and secondary parkinsonian syndromes. The decrease correlated with the severity of PD, measured by the UPDRS (r = -0.54; P < 0.05). Glutamate level was increased in platelets of PD patients, but was not correlated to the uptake decrease. Both phoenomena may be explained by the modifications of mitochondrial enzymes described in platelets, which could be used as a peripheral model of glutamatergic function in PD.

Analysis of Variance↗
PubMed1999

Benzodiazepine-induced chemotaxis is impaired in monocytes from patients with generalized anxiety disorder.

Peripheral benzodiazepine receptors (PBR) modulate chemotaxis and cytokine production of monocytes and lymphocytes. Since PBR are decreased in animal models of stress and in patients with anxiety disorders, in the present study we analyze the ability of monocytes obtained from patients suffering from generalized anxiety to migrate towards chemoattracting benzodiazepines. In these patients, the benzodiazepine-induced chemotaxis is completely abolished, while the response to the control chemoattractant formyl-leu-met-phe is still maintained. The chemotaxis responses are not restored after pharmacological treatment of the pathology. The decreased chemotactic response could be linked to a decreased number of PBR receptors present on monocytes of generalized anxiety disorder patients.

Adult↗
PubMed1999

Increased cytokine release from peripheral blood cells after acute stroke.

Cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha can play pathogenetic or protective roles in stroke. They are increased in the brain after experimental ischemia and in the CSF of patients with stroke. However, their presence in the periphery is still controversial. To determine the source and time-course of cytokines in blood of stroke patients, IL-6 and TNF-alpha release from blood cells and serum levels were determined in 40 patients on days 1 through 2, 4, 10, 30, and 90 after stroke. Twenty healthy age-matched volunteers were used as controls. IL-6 and TNF-alpha release from stimulated blood cells was increased in stroke patients, compared to controls. A peak response (+224%) was observed at day 4 for IL-6, while TNF-alpha release was largely and significantly increased (about three-fold compared to controls) from day 1 to 2 until day 90 after stroke. The increase in IL-6 release was significantly higher in ischemic, compared to hemorrhagic strokes, at days 1 and 4. Circulating IL-6 was increased at each time point. The ischemic processes in the CNS induces a long-lasting activation of IL-6 and TNF-alpha production in peripheral blood cells, which are a major source of serum cytokines after stroke.

Acute Disease↗
PubMed1999

Rational use of EEG in adults in clinical practice.

The electroencephalogram (EEG) is still widely used for the diagnosis of several clinical conditions and symptoms. To assess the information provided by the EEG in relation to its duration, and to identify the shortest recording providing a conclusive report, the tracing was tested in 290 adult patients seen in a hospital neurophysiology unit for epilepsy (definite or uncertain), headache, head trauma, fainting, syncope, undefined loss of consciousness, vertigo, and cerebrovascular disease. Two neurophysiologists participating in the study read the same EEG independently. The record was based on a standardized timed sequence of montages. At each step any changes from the previous step were noted. Sixty-seven percent of the EEGs were coded as normal or aspecific, 24.1% were slow, and 8.6% were epileptiform. Normal tracings ranged from 38.8% (definite epilepsy) to 87.5% (vertigo), and epileptiform EEG from 0 (uncertain epilepsy) to 28.6% (definite epilepsy). The final report was clear in 80% of cases at the end of a 2-minute reading and almost 90% after 4 minutes. Hyperventilation and intermittent photic stimulation contributed little to the final report. Only for definite epilepsy were there changes along the whole sequence of montages. Thus, only for epilepsy need the EEG recordings last more than 20 minutes, whereas for the other clinical indications the total recording time could be limited to 4 minutes at most.

Adolescent↗
PubMed1999

Chronic axonal sensory and autonomic polyneuropathy without motor involvement: a new 'chronic inflammatory neuropathy?'.

We report the case of a woman with axonal sensory and autonomic neuropathy lasting several months who improved in association with steroid administration. During the course of her disease and in the follow-up, the patient underwent repeated cerebrospinal fluid (CSF) examinations, neurophysiological somatic, autonomic nervous system studies and sural nerve biopsy. Clinical and laboratory assessments demonstrated the occurrence of a monophasic, chronic sensory and autonomic neuropathy. A sural nerve biopsy suggested an axonopathy. After a progressive worsening of symptoms lasting about 6 months, steroid treatment was started and within 6 months a complete recovery, with normalization of the CSF findings, was observed. Although the 'chronic inflammatory neuropathies' are still debated entities, the features of this chronic, exclusively sensory and autonomic neuropathy are new, and the occurrence of a high protein level in the CSF, together with the favorable outcome associated with steroid treatment, suggests that our case might be another variant in this debated area.

Autonomic Nervous System Diseases↗
PubMed1999

Cisplatin-induced DNA-platination in experimental dorsal root ganglia neuronopathy.

The mechanism(s) and site(s) of the neurotoxic effect of cisplatin (CDDP) are still not entirely elucidated. A more detailed knowledge of these aspects of CDDP treatment might be useful to obtain a better understanding of the pathogenesis of its peripheral neurotoxicity, which is the dose-limiting side effect of CDDP. In the present study, the occurrence of CDDP-induced DNA-platination in dorsal root ganglia (DRG) of rats was evaluated in relation to DRG neuron pathological changes and CDDP-induced neuronopathy. Eight adult Wistar rats were treated with 2 mg/kg i.p. CDDP twice weekly for 9 times to induce sensory peripheral neuropathy. DNA-platination in specimens of DRG and kidney was measured immunohistochemically, with a polyclonal antibody (GPt) detecting CDDP-induced Pt-DNA adducts. Results were compared with those of untreated rats. Chronic CDDP-induced neurotoxicity, in a well described experimental model of chronic CDDP neurotoxicity in the Wistar rat, was confirmed by sensory DRG neuronopathy with secondary neuropathy, and demonstrated by reduced pain detection, decreased nerve conduction velocity in the tail nerve as well as morphological and morphometric changes in DRG neurons. Nuclear immunostaining for Pt-DNA adducts was observed in tubular cells of the kidney in 75% of the evaluated CDDP-treated rats, while in DRG cells CDDP-induced Pt-DNA adducts formation was found in 43% of the evaluated CDDP-treated rats. CDDP-induced DNA-platination was demonstrated in rat DRG neurons using a schedule of chronic CDDP administration which induced the onset of a sensory neuronopathy with secondary peripheral neuropathy. This finding further supports the hypothesis that CDDP is neurotoxic because it directly damages the DRG neurons.

Animals↗
PubMed1998

Diazepam binding inhibitor (DBI) in the plasma of pediatric and adult epileptic patients.

The polypeptide diazepam binding inhibitor (DBI) displays epileptogenic activity by binding to benzodiazepine receptors. We analyzed DBI concentrations in the plasma of pediatric and adult epileptic patients, as a possible peripheral marker in epilepsy. DBI plasma concentrations are significantly higher (+ 62%, P < 0.001) in adult patients and slightly but significantly higher (+15%, P < 0.01) in pediatric patients, compared to age-related controls. Strikingly, plasma DBI is much higher (+81%, P < 0.001) in generalized epilepsy in adults and in drug-resistant pediatric and adult patients. Based on these findings, plasma DBI may be considered as a peripheral biological marker of epilepsy and, in association with lymphocyte benzodiazepine receptor density, of anticonvulsant drug responsiveness.

Adolescent↗
PubMed1998

Carboplatin toxic effects on the peripheral nervous system of the rat.

BACKGROUND: The most striking of carboplatin's advantages (CBDCA) over cisplatin (CDDP) is its markedly reduced rate of neurotoxic effects. However, the use of CBDCA higher-intensity schedules and the association with other neurotoxic drugs in polychemotherapy may cause some concern about its safety with respect to peripheral nervous system damage. MATERIALS AND METHODS: Two different schedules of CBDCA administration (10 mg/kg and 15 mg/kg i.p. twice a week for nine times) were evaluated in Wistar rats. Neurotoxicity was assessed for behavioral (tail-flick test), neurophysiological (nerve conduction velocity in the tail nerve), morphological, morphometrical and analytical effects. RESULTS: CBDCA administration induced dose-dependent peripheral neurotoxicity. Pain perception and nerve conduction velocity in the tail were significantly impaired, particularly after the high-dose treatment. The dorsal root ganglia sensory neurons and, to a lesser extent, satellite cells showed the same changes as those induced by CDDP, mainly affecting the nucleus and nucleolus of ganglionic sensory neurons. Moreover, significant amounts of platinum were detected in the dorsal root ganglia and kidney after CBDCA treatment. CONCLUSIONS: CBDCA is neurotoxic in our model, and the type of pathological changes it induces are so closely similar to those caused by CDDP that it is probable that neurotoxicity is induced in the two drugs by the same mechanism. This model can be used alone or in combination with other drugs to explore the effect of CBDCA on the peripheral nervous system.

Animals↗
PubMed1998

[Neurology].

Explore the source record for details and available documents.

Cerebrovascular Disorders↗
PubMed1997

Decreased density of lymphocyte benzodiazepine receptors in drug-resistant epileptic patients.

Peripheral benzodiazepine receptors (PBR) may have a role in epilepsy and in mediating antiepileptic drug effects. Since PBR in blood mononuclear cells may be acted on by anticonvulsant drugs, we investigated possible modifications of these receptors in newly diagnosed patients, before and after antiepileptic treatment and in drug-resistant epileptic patients. A significantly lower receptor density, with no difference in affinity, was observed in drug-resistant patients, compared to newly diagnosed patients and to normal age-related controls. We suggest the possible use of PBR as a peripheral marker of drug response.

Adult↗
PubMed1997

Which diagnostic procedures in the elderly? The case of late-onset Huntington's disease.

The typical adult-onset form of Huntington's disease (HD) is a clinical condition in which the latest advances of genetic research can be usefully applied during the course of the diagnostic process; not so clear are the guidelines for the much less frequent late-onset variant. We have recently seen three patients in their late sixties who had been misdiagnosed for up to 10 years due to the apparently isolated, mild, and slowly progressive nature of their hyperkinetic movements or cognitive disorders. Only after the results of DNA sequencing on a blood sample became available could the appropriate diagnosis of late-onset HD be reached. By contrast, neuroimaging studies lacked sufficient sensitivity and specificity. Appropriate neurogeriatric assessment in these cases should follow specific guidelines and should always include selected high-technology procedures.

Aged↗
PubMed1996

Modifications of diazepam binding inhibitor and peripheral benzodiazepine receptors in the lymphocytes of epileptic patients.

Recent experimental evidence has suggested that peripheral benzodiazepine receptors (PBR) may play a role in epilepsy and antiepileptic drug action. Since PBR are also present in circulating lymphocytes, and may interact with anticonvulsant drugs, this study was designed to look for possible modifications of these receptors and their endogenous ligand diazepam binding inhibitor (DBI) in the lymphocytes of epileptic patients treated with various drugs. PBR levels were 50% to 80% higher in patients treated with carbamazepine, phenobarbital and valproic acid than in controls and untreated epileptics. DBI levels were significantly increased in the lymphocytes of untreated patients, and showed only a slight further increase after anticonvulsant therapy. The possibility that PBR and DBI modifications in the lymphocytes of epileptic patients may be linked to the immunological alterations reported in these patients and/or may represent possible markers of neurochemical modifications in the central nervous system is discussed.

Adolescent↗
PubMed1996

Effects of sensory aids on the quality of life and mortality of elderly people: a multivariate analysis.

The present study aimed at clarifying the relationships between the use of sensory aids and the quality of life (QOL) and mortality of elderly people suffering from sensory deprivation. We carried out a cross-sectional survey on the QOL and the sensory status of an elderly cohort and a 6-year longitudinal follow-up of mortality rates among 1192 non-institutionalized people aged 70-75 years in a North Italian town. We classified respondents into three groups: those with functionally adequate visual and hearing acuity (n = 275); those with sensory impairment, corrected by the use of sensory aids (n = 680), and those with uncorrected sensory impairment (n = 245). In the whole sample, multiple logistic regression analyses showed that an uncorrected sensory deprivation was associated with a significant and independent impairment of mood, self-sufficiency in instrumental activities of daily living and social relationships. Such impairments were not apparent in the subjects with sensory impairments who were using sensory aids. In men with uncorrected sensory impairment the unadjusted 6-year mortality rate was almost twice that of the other two groups, which did not differ from each other. No corresponding differences were detected in women. Multivariate analysis showed that the effect of the sensory aid status on mortality was indirect and mediated through the global physical health status and the social relationships. We conclude that our cross-sectional data demonstrate an association between uncorrected sensory deprivation and a low QOL; such an association was not present in subjects with corrected sensory deprivation.

Activities of Daily Living↗
PubMed1996

Posatirelin in the treatment of vascular dementia: a double-blind multicentre study vs placebo.

INTRODUCTION: The usefulness of posatirelin (L-pyro-2-aminoadipyl-L-leucyl-L-prolinamide), a synthetic peptide having modulatory activity on the monoaminergic and cholinergic systems and neurotrophic effects, was evaluated in vascular dementia. PATIENTS AND METHODS: A multicentre, parallel groups, double-blind clinical study vs placebo was carried out with patients suffering from probable vascular dementia according to the NINDS-AIREN criteria. The study consisted of a two-week run-in of a once daily, orally administered, placebo phase, followed by 12 weeks of intramuscular treatment with posatirelin 10 mg/ml or placebo given once a day and a follow-up after one month's withdrawal. Efficacy was assessed using the Gottfries-Bråne-Steen (GBS) Rating Scale for dementia, the Randt Memory Test and the Toulouse-Piéron Attention Test. Data were evaluated using analysis of variance and covariance. RESULTS: As regards GBS scores, patients treated with posatirelin showed a significant improvement in intellectual performance, in orientation, motivation and memory as compared to controls. The improvement of memory performance was also confirmed by the acquisition score and memory index of the Randt Memory Test. At the end of the follow-up period the differences between treatments were still maintained. Tolerability was good. CONCLUSIONS: The significant improvement observed in cognitive functions, attention and motivation of demented patients treated with posatirelin suggests the potential usefulness of this drug in vascular dementia. Furthermore, the presence of a long-lasting effect after drug withdrawal suggests the possibility of administering the drug cyclically.

Aged↗