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Biomedical subjects

A Quattrone

Publications and source records attributed to A Quattrone.

At least 145 records · Page 8Linked to original sources

Cationic lipids improve antisense oligonucleotide uptake and prevent degradation in cultured cells and in human serum.

The power of antisense phosphodiester oligonucleotides (aODN) as regulatory molecules of gene expression is strongly limited by their low cellular uptake and very rapid nuclease-mediated degradation. This study deals with the effect of artificial cationic lipids on ODN cellular uptake and degradation in cell cultures and in human serum. At the ODN levels normally used in antisense-mediated gene regulation experiments, a cationic lipid, DOTAP, enhances the rate of ODN uptake more than 25 fold, but at lower ODN levels the effect of DOTAP is absent. These findings are consistent with a mechanism of ODN internalization by receptor-mediated saturable endocytosis that is bypassed by DOTAP. ODN degradation by nucleases is markedly prevented by DOTAP both in cultured cells and in human serum. Other cationic lipids, namely DOTMA and DOGS, exhibit very similar behaviour. The relatively slight cellular toxicity revealed by cationic lipids contribute to render these molecules very suitable for aODN vehiculation.

3T3 Cells↗

Age and GSH metabolism in rat cerebral cortex, as related to oxidative and energy parameters.

A comprehensive study on GSH metabolism in relation to some markers of oxidative and energy status in rat cerebral cortex as a function of age was performed. Reduced GSH, total GSH and the GSH Redox Index decreased both during growth (defined as the period between 1 and 5 months) and during aging (defined as the period between 5 and 27 months) while GSSG levels increased during the two periods, but most significantly during aging. Also GSH-associated enzymes and adenine-pyridine nucleotide levels show age characteristic changes. The obtained results suggest that decreases in oxidative and energy metabolism occur during aging. They probably contribute to decreases in the activity of the biosynthetic processes (i.e., NADP+(H) and GSH synthesis) and in the antioxidant capacity of the GSH system. However, the oxidative stress does not seem to be a typical characteristic of the aging period; as an oxidative status is present during the growth period too. Typical parameters of aging process are mainly the low levels of reduced GSH, total GSH and GSH Redox Index and the high levels of GSSG as well as the high levels of GSH peroxidase and GSH transferase and the low levels of gamma-glutamylcysteine synthetase.

Adenosine Diphosphate↗

Functional integrity of benzodiazepine receptors of the geniculo-striate visual pathways in Creutzfeldt-Jakob disease. A pharmacological evoked potential study.

We evaluated the effects of flumazenil (FMZ), a high-affinity benzodiazepine receptor antagonist, on flash-evoked visual potentials (FEPs) in a patient with Creutzfeldt-Jacob disease (CJD). FEPs were recorded in three different consecutive sessions: (1) basal condition, without any pharmacological treatment; (2) 3.5 min after i.v. administration of 5 mg FMZ; (3) 1 min after i.v. administration of 10 mg diazepam (DZP). FMZ provoked a marked increase in the amplitude as well as evident shortening of the latency of early FEP components. DZP reversed these effects. These results are in agreement with our previous findings of anatomical and functional integrity of the geniculo-striate pathways in human CJD and demonstrate functional integrity of benzodiazepine receptors in this visual system in CJD.

Creutzfeldt-Jakob Syndrome↗

Oral pulse levodopa therapy in mild Parkinson's disease.

Chronic levodopa administration in Parkinson's disease (PD) is associated with long-term motor side effects. To reduce the cumulative amount of levodopa intake by patients with mild PD, we investigated the clinical efficacy of short periods of treatment with levodopa scheduled at different daily dosages and administered in a conventional design (ie, three times a day) compared with a standard oral dose of the drug administered once every 3 days. The latter dose regimen, designated "oral pulse levodopa therapy" (OPLT), allowed us to obtain a clinical response comparable to that obtained by conventional treatments that involve cumulative daily levodopa dosages up to seven times higher than OPLT. The clinical efficacy of OPLT could be related to the preservation of compensatory mechanisms in Parkinson's disease that are masked by conventional intermittent replacement therapy.

Administration, Oral↗

Saccadic eye movements analysis in the early diagnosis of myasthenia gravis.

Saccadic eye movements were examined by electro-oculography in 21 patients with suspected myasthenia gravis. The presence of dissociated nystagmus and quiver eye movements was also assessed. The aim of the study was to assess the diagnostic value of saccadic abnormalities in the early stage of the disease. Pathological oculographic findings consisted of intra and post saccadic disorders and intersaccadic variability. A fatigue test was useful in detecting latent disorders in most patients. A Tensilon test was positive in 11 out of 16 patients with oculographic abnormalities. Diagnostic problems, apparently paradoxical findings and differential involvement of extraocular muscle fibers are discussed.

Adolescent↗

Different susceptibilities of the geniculate and extrageniculate visual pathways to human Creutzfeldt-Jakob disease (a combined neurophysiological-neuropathological study).

Flash evoked visual potentials (FEPs) of 7 patients with advanced Creutzfeldt-Jakob disease (CJD) were compared with those recorded in 7 patients with senile dementia of the Alzheimer type (SDAT), in 13 age- and sex-matched healthy volunteers and in 7 neuropsychiatrically normal subjects whose occipital evoked responses were increased in amplitude (amplitude controls). Post-mortem examination was performed in 4 of 7 CJD patients in order to map pathological changes along the visual pathways, including the retino-geniculo-striate and extrageniculate pathways. Normal FEPs were typified by 2 constant early components (P1 and N2) followed by several (3 or more) late components that were characterized by marked interindividual variability. Amplitude controls had enlarged (from 14 to 44.8 microV, mean 25.7) P1 component. Both SDAT and CJD patients had normal early FEP waves (P1 and N2) and important alterations of the late FEP components. Moreover, a late positive component was responsible for abnormally enlarged FEPs (52.6 and 58.2 microV) in 2 CJD patients. Finally, electroretinograms, recorded in 1 CJD patient, were normal. These findings suggested relative functional integrity of the retino-geniculo-striate pathway associated with important dysfunction of the cortical visual processing in both SDAT and CJD patients. Pathological studies disclosed preservation of optic nerves, chiasmas, lateral geniculate nuclei and Gennari's strip of the striate cortex but associated with important spongiform change, neuronal loss and gliosis in the superior colliculi (layer II), pulvinar, extrastriate cortex and layers II-III, V and VI of the striate cortex. We conclude that different visual pathways have different susceptibilities to CJD: important functional and anatomical alterations of the intracortical and extrageniculate pathways contrast with relative preservation of the retino-geniculo-striate pathway.

Adult↗

Sensory evoked potentials in herpes simplex encephalitis.

Flash visual potentials (FEPs), somatosensory evoked potentials (SEPs) and auditory brainstem responses (ABR) were recorded in a 66-year-old patient presenting with clinical, EEG and CT brain scan features of herpes simplex encephalitis (HSE). At the time of evoked potential study (10 days after onset of the disease) the patient was treated with iv barbiturate on controlled respiration (lidocaine and phenytoin were not utilized); core temperature was 37 degrees C and pupils were dilated and nonreactive. Cortical FEPs were not recognizable on 02 lead, whereas they were clearly evident on 01 with normal latency of early N1, P1, N2 waves and delayed P2 component. SEPs showed normal peripheral and central conduction times, but N20 peak was bilaterally absent with unrecognizable (on P3) or delayed (on P4) N33 wave. No ABR (including wave I) were found on stimulation of the right ear, whereas delayed wave V with prolonged interpeak I-V latency was found on stimulation of the left ear. In conclusion, changes in sensory evoked potentials in HSE seem to be caused either by necrotic-hemorrhagic damage (with the disappearance of some cortical responses), by coma (with alterations in middle-latency cortical responses) and by increased intracranial pressure (with subsequent ABR abnormalities).

Aged↗

Sleep-induced masticatory myoclonus: a rare parasomnia associated with insomnia.

Tonic and rhythmic activity of the masticatory muscles accompanied by a loud and grating or clicking sound characterizes bruxism, a well-recognized parasomnia. We describe a 63-year-old man who complained of insomnia due to repeated tongue nibbling during sleep. Nocturnal polysomnographic recordings showed brief (50-100-ms) myoclonic jerks of myloioideus and masseter muscles occurring during phase 1 of sleep and leading to troublesome tongue nibbling with arousal of the patient. Hypnograms showed reduction of phase 2 and absent phases 3-4 and REM. Different pharmacological treatments including clomipramine, benzodiazepines, and carbamazepine were ineffective. A purposive interdental plate was placed to prevent jaw closings during sleep: masticatory myoclonus still persisted, but it did not provoke arousals; insomnia disappeared and night hypnograms improved.

Cerebral Cortex↗

Transformation by ras oncogene induces nuclear shift of protein kinase C.

We measured protein kinase C (PKC) activity in normal and ras-transformed Balb/3T3 fibroblasts; cytosolic and nuclear-associated PKC activity was determined either as phorbol ester binding, PKC-dependent phosphorylation of histone III-S, or phosphorylation of endogenous nuclear proteins. Results demonstrate that ras-transformed fibroblasts show down-regulation of cytosolic PKC accompanied by increase of nuclear-associated PKC. These results provide evidence linking transformation to PKC nuclear shift with consequent phosphorylation of nuclear proteins.

Animals↗

Triphasic waves and cerebral tumors.

Three patients with cerebral tumor involving diencephalic midline structures (2 malignant gliomas, 1 craniopharyngioma) and no metabolic abnormalities developed disorientation in time and place or coma with triphasic waves (TW) seen on electroencephalograms. Serial EEG recordings showed persistence or disappearance of TW depending on poor or good outcome of the antiedema treatment. TW have been described with disorders affecting the brain diffusely, as metabolic encephalopathies, dementing processes, cerebral carcinomatosis and baclofen intoxication. The findings described here demonstrate that TW may occur in patients with brain tumor involving subcortical midline structures.

Aged↗

Sensory evoked potentials in Creutzfeldt-Jakob disease.

Eight patients presenting with intermediate or terminal evolution of Creutzfeldt-Jakob disease (CJD) were investigated by means of evoked potentials. Fifteen age-matched healthy subjects served as controls. The 8 patients had well-recognizable but simplified flash evoked potentials (FEPs) consisting of P1 and N2 waves followed by a single late positive (P2) deflection. Enlarged FEPs were found in 2 of the 8 patients. The somatosensory central conduction time was normal in 3 of 5 patients, and it resulted in upper normal limits or was moderately slowed in 2 patients. No enlarged somatosensory scalp potentials were recorded. Cortical somatosensory responses were characterized by an unrecognizable (4 patients) or delayed (2 patients) N33 wave. Brainstem auditory evoked responses, recorded in 6 patients, were normal. In CJD very important functional impairment of the sensory cortical areas is associated with absent or mild dysfunction of the subcortical sensory pathways.

Acoustic Stimulation↗

Nonmetabolic causes of triphasic waves: a reappraisal.

Two more patients with triphasic waves (TW) on their EEGs in the absence of metabolic disturbances are described. One patient had coma associated with cerebellar hematoma, the other had mild dementia associated with idiopathic calcifications of the basal ganglia and normal auditory brainstem responses, subcortical and cortical somatosensory evoked potentials. Neurologic examination failed to show asterixis in both patients. The literature on nonmetabolic causes of TW was also reviewed, and the clinical and anatomic reports of 10 patients have been analyzed: 7 patients had focal brainstem-diencephalic lesions (craniopharyngioma: 2 patients; thalamic gliomas: 3 patients; pontine stroke: 2 patients), and 3 patients suffered from diffuse subcortical or multifocal encephalopathies (Binswanger's encephalopathy: 1 patient; cerebral carcinomatosis: 1 patient; multifocal cerebral lymphoma: 1 patient). From the clinical point of view, patients with nonmetabolic diseases causing TW presented either disturbance of higher cerebral functions with no asterixis or sudden onset of coma. It is concluded that TW may result from focal brainstem/diencephalic lesions or from diffuse subcortical or multifocal encephalopathies in the absence of concomitant metabolic abnormalities. Nonmetabolic causes of TW should be suspected in patients presenting with neurologic disturbances not associated with asterixis.

Aged↗

Computer analysis of saccadic eye movements: assessment of two different carbamazepine formulations.

The central effects of two different formulations of Carbamazepine (CBZ) have been examined by analysis of saccadic eye movements (SEM) in 6 healthy volunteers, who took part in a double-blind, latin-square, placebo controlled study. Both a conventional- and a controlled-release formulation of CBZ produced a significant effect on peak saccadic velocity and saccade accuracy, but only the former affected saccade latency. Computer analysis of SEM confirmed it to be a highly sensitive method for detection of subclinical drug effects on the CNS.

Adult↗

The contribution of saccadic eye movements analysis, visual and auditory evoked responses to the diagnosis of multiple sclerosis.

A number of tests have been used to identify paraclinical evidences of central nervous system (CNS) lesions in multiple sclerosis (MS). The present study was aimed to test and compare the diagnostic value of saccadic eye movements (SEM) analysis, and visual and auditory brain stem evoked responses (VER, ABER) in MS, and to study the correlation between electrophysiologic findings and clinical data. The reference group for epidemiological and statistical analysis was selected from the group of 109 suspected MS patients included in the study. SEM analysis resulted at least as sensitive as VER and ABER. SEM analysis showed good sensitivity and positive predictive value. Saccade latency resulted the most sensitive SEM parameter. Subclinical internuclear ophthalmoparesis resulted highly specific. We suggest that SEM analysis could be included into the electrophysiologic tests for identifying paraclinical evidences of CNS lesions in MS. Correlations between electrophysiologic findings and clinical data are discussed.

Adolescent↗

Combined neurophysiological studies in Creutzfeldt-Jakob disease: a case report.

EEG and brain mapping (on basal conditions and after i.v. administration of diazepam) and visual, somatosensory and auditory evoked potentials have been performed on a patient at terminal evolution of CJD. These combined neurophysiologic studies indicated that very important functional impairments of either thalamic-frontal circuits and frontal, parietal and occipital cortex were associated with absent or mild dysfunction of the visual, somatosensory and auditory subcortical pathways. Combined neurophysiologic studies are important to better understand the pathophysiologic mechanisms of neurodegenerative diseases.

Aged↗