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Biomedical subjects

G Gobbi

Publications and source records attributed to G Gobbi.

At least 19 recordsLinked to original sources
PubMed2006

Effects of oxcarbazepine on cognitive function in children and adolescents with partial seizures.

The authors investigated the effect of oxcarbazepine on cognitive function in children and adolescents (6 to younger than 17 years of age) with newly diagnosed partial seizures in an open-label comparison with standard antiepileptic drug therapy (carbamazepine and valproate). No differences in cognitive tests were observed between oxcarbazepine and carbamazepine/valproate over a 6-month treatment period.

Adolescent↗
PubMed2005

Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis.

Although anecdotal reports suggest that cannabis may be used to alleviate symptoms of depression, the psychotropic effects and abuse liability of this drug prevent its therapeutic application. The active constituent of cannabis, delta9-tetrahydrocannabinol, acts by binding to brain CB1 cannabinoid receptors, but an alternative approach might be to develop agents that amplify the actions of endogenous cannabinoids by blocking their deactivation. Here, we show that URB597, a selective inhibitor of the enzyme fatty-acid amide hydrolase, which catalyzes the intracellular hydrolysis of the endocannabinoid anandamide, exerts potent antidepressant-like effects in the mouse tail-suspension test and the rat forced-swim test. Moreover, URB597 increases firing activity of serotonergic neurons in the dorsal raphe nucleus and noradrenergic neurons in the nucleus locus ceruleus. These actions are prevented by the CB1 antagonist rimonabant, are accompanied by increased brain anandamide levels, and are maintained upon repeated URB597 administration. Unlike direct CB1 agonists, URB597 does not exert rewarding effects in the conditioned place preference test or produce generalization to the discriminative effects of delta9-tetrahydrocannabinol in rats. The findings support a role for anandamide in mood regulation and point to fatty-acid amide hydrolase as a previously uncharacterized target for antidepressant drugs.

Animals↗
PubMed2005

Chromosome 18 aberrations and epilepsy: a review.

Epilepsy is commonly observed in patients with chromosomal aberrations. We evaluated epilepsy and electroencephalographic (EEG) features in a group of patients carrying aberrations of chromosome 18. Fourteen patients were recruited: five with an 18p deletion syndrome (18pDS); six with an 18q deletion syndrome (18qDS); two with trisomy 18p syndrome; and one with a 45,XY,t(17-18) (cen-q11.2) karyotype. Patients with 18pDS had neither epilepsy nor EEG anomalies; four patients with 18qDS had epilepsy with partial seizures occurring during infancy or early childhood. Partial seizures were also present in both patients with trisomy 18p. By contrast, mixed seizures were observed in the patient carrying a translocation between chromosomes 17 and 18. Our data and a re-evaluation of the literature suggest that epilepsy is infrequent in patients with 18pDS. Conversely, partial seizures and focal EEG anomalies may be observed in those with patients with 18qDS. Our observations suggest that the haplo-insufficiency of genes located on the long arm of chromosome 18 is more likely to be associated with epilepsy, than is haplo-insufficiency of genes located on the short arm. While further EEG/clinical investigations are needed to validate these observations, this study indicates a possible relationship between chromosome 18 genes and epilepsy.

Adolescent↗
PubMed2004

Anti-brain but not celiac disease antibodies in Landau-Kleffner syndrome and related epilepsies.

The Landau-Kleffner syndrome, the continuous spikes-waves during slow sleep syndrome and the benign epilepsy of childhood with rolandic spikes are rare childhood epilepsies with unknown etiology. Improvement in patients treated with immunoglobulin suggests an involvement of the immune system. We provide immunohistochemical evidence of autoantibodies against rat brain auditory cortex, brainstem and cerebellum, in children suffering with one or more of these syndromes. Only 1/14 patient was celiac.

Adolescent↗
PubMed2004

The response of human natural killer cells to interleukin-2.

Natural killer cells play a key role in the defence of organisms against virus infections and in the control of tumor onset. Interleukin-2 is a multifunctional inflammatory cytokine able to activate natural killer cells, essentially inducing cell proliferation, lymphokine-activated-killer cell generation and cytokine production. Here we discuss some signaling events generated by interleukin-2 in the cell nucleus of primary human natural killer cells, specifically focusing on the lipid signal transduction and the induction of the cyclic adenosine-5'-monophosphate response element binding protein transcription factor. The implications of these nuclear events in the response of natural killer cells to interleukin-2 are also discussed.

Animals↗
PubMed2003

Experience with immunomodulatory treatments in Rasmussen's encephalitis.

The authors investigated immunomodulatory treatments in 15 patients with Rasmussen encephalitis (RE) (14 with childhood and one with adolescent onset RE). Positive time-limited responses were obtained in 11 patients using variable combinations of corticosteroids, apheresis, and high-dose IV immunoglobulins. Although surgical exclusion of the affected hemisphere is the only treatment that halts disease progression, immunomodulation can be considered when early surgery is not feasible, in late-onset patients with slower disease progression, and in the few cases of bilateral disease.

Adolescent↗
PubMed2003

Diagnostic imaging in 13 cases of Rasmussen's encephalitis: can early MRI suggest the diagnosis?

Rasmussen's encephalitis (RE) is a rare, progressive, chronic encephalitis characterised by drug-resistant epilepsy, progressive hemiparesis and mental impairment. It typically involves only one cerebral hemisphere, which becomes atrophic. We present neuroradiological findings in 13 children with RE. MRI was performed in all patients, fluorodeoxyglucose positron-emission tomography (PET) in three, Tc-99m hexamethylpropylenamine oxime single-photon emission computed tomography (SPECT) in two and proton MR spectroscopy ((1)HMRS) in two. MRI showed progression of the hemisphere atrophy, always prevalent in the region primarily involved (13 patients), spread of the abnormal signal in white matter (11) and cortex (10) and progression of atrophy of the head of the caudate nucleus (nine). Associated secondary changes were: atrophy of the contralateral cerebellar hemisphere (in four patients), the ipsilateral hippocampus (in five) and the brain stem (in five). The earliest CT and MRI abnormalities, seen between 1 day and 4 months after the first seizure (in 12 patients examined, nine of whom had MRI) in one cerebral hemisphere included: high signal on T2-weighted images in the cortex (seven patients) and white matter (nine), cortical atrophy usually involving the frontoinsular region, with mild or severe enlargement of the lateral ventricle (eight) and moderate atrophy of the head of the caudate nucleus (seven). Cortical swelling in the early stage of the disease was recognisable only in two patients. PET revealed hypometabolism, SPECT decreased perfusion, and (1)HMRS reduction of N-acetylaspartate in the affected hemisphere. PET and SPECT were usually performed in the late stages and did not provide specific findings. MRI thus demonstrates the progression of RE and may suggest the diagnosis in the early stages, often before the appearance of neurological deficits. Early diagnosis of RE may be crucial for selecting patients for aggressive medical therapy or major surgical interventions such as hemispherectomy.

Atrophy↗
PubMed2003

Rasmussen's encephalitis: early characteristics allow diagnosis.

OBJECTIVE: To identify early manifestations of Rasmussen encephalitis (RE) that can prompt early and reasonably secure diagnosis, allowing medical or surgical therapies at an early stage when they may be more effective in slowing the disease. METHODS: The authors studied 12 patients with clinical and neuropathologic diagnosis of RE, followed from disease onset, assessing clinical history, imaging, and EEG and focusing on early characteristics. Anti-GluR3 antibody assays were also considered in 11 patients. RESULTS: By 4 months from first symptoms, all cases had 1) refractory focal seizures with a predominant motor component, 2) slow focal activity on EEG contralateral to the motor manifestations, and 3) focal contralateral white matter hyperintensity with insular cortical atrophy on neuroimaging. Less constant or later findings were epilepsia partialis continua, oligoclonal bands, and serum anti-GluR3 antibodies. CONCLUSIONS: The association of partial seizures with focal EEG and neuroimaging changes allows a tentative diagnosis of RE 4 to 6 months after first symptoms.

Adolescent↗
PubMed2002

Localized (1)H magnetic resonance spectroscopy in mainly cortical gray matter of patients with multiple sclerosis.

The brain water fraction (R), the brain water transverse relaxation time (T2), the atrophy index (alpha) and the absolute concentration of the principal brain metabolites (NAA, Cho and Cr) were measured by localized proton magnetic resonance spectroscopy in the occipito-parietal cortex (mainly gray matter) of 15 relapsing-remitting (R-R) multiple sclerosis (MS) patients, 15 secondary progressive (SP) MS patients and 8 healthy subjects. Significantly lower values of N-acetylaspartate (NAA), creatine (Cr) and the NAA/Cr ratio in the occipito-parietal cortex were detected in SP MS patients than in R-R MS and control subjects (p < 0.01). Moreover, MS patients showed shorter T2 water relaxation times and reduced brain water fraction compared with controls. Higher atrophy indices were also detected in the mainly occipito-parietal gray matter of MS patients, particularly in those with the progressive form. These findings suggest that the pathological process in MS is not limited to either white matter lesions or normal-appearing white matter but extends into the cortical gray matter (occipito-parietal), particularly in the progressive form of the disease. This can involve changes in neural metabolism or neural shrinkage and neuron loss. The significant increase in atrophy indices could be the expression of the relatively higher cerebrospinal fluid signal from the occipito-parietal cortex, even in the absence of obvious cortical atrophy.

Adult↗
PubMed2001

(1)H-MR spectroscopy differentiates mild cognitive impairment from normal brain aging.

This study aimed to characterize the white matter biochemical profile of healthy elderly subjects, mild cognitive impairment (MCI) subjects, and early Alzheimer's disease (AD) patients. We used proton magnetic resonance spectroscopy ((1)H-MRS) to measure myo-inositol, creatine, N-acetylaspartate (NAA) and choline levels from a volume of interest located in the paratrigonal white matter bilaterally. A significantly higher myo-inositol/creatine ratio was found in MCI subjects and AD patients than in controls. The NAA/creatine ratio was reduced in AD patients in the left hemisphere compared to control subjects. The choline/creatine ratio was not significantly different among the three groups. These data suggest that MCI is different from normal brain aging, having a white matter biochemical pattern similar to AD.

Aged↗
PubMed2001

Genetic and pharmacological disruption of neurokinin 1 receptor function decreases anxiety-related behaviors and increases serotonergic function.

Alterations in serotonin (5-hydroxytriptamine, 5-HT), norepinephrine, and gamma-aminobutyric acid have been linked to the pathophysiology of anxiety and depression, and medications that modulate these neurotransmitters are widely used to treat mood disorders. Recently, the neuropeptide substance P (SP) and its receptor, the neurokinin 1 receptor (NK1R), have been proposed as possible targets for new antidepressant and anxiolytic therapies. However, animal and human studies have so far failed to provide a clear consensus on the role of SP in the modulation of emotional states. Here we show that both genetic disruption and acute pharmacological blockade of the NK1R in mice result in a marked reduction of anxiety and stress-related responses. These behavioral changes are paralleled by an increase in the firing rate of 5-HT neurons in the dorsal raphe nucleus, a major source of serotonergic input to the forebrain. NK1R disruption also results in a selective desensitization of 5-HT1A inhibitory autoreceptors, which resembles the effect of sustained antidepressant treatment. Together these results indicate that the SP system powerfully modulates anxiety and suggest that this effect is at least in part mediated by changes in the 5-HT system.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2001

Clonidine fails to modify dopaminergic neuronal activity during morphine withdrawal.

RATIONALE: Cellular substrates of opiate withdrawal syndrome involve several brain areas, in particular the mesolimbic dopaminergic and noradrenergic systems, but the interactions between the two pathways remain unclear. OBJECTIVES: The aim of the present work was to investigate the effects of the alpha2-agonist clonidine on ventral tegmental area dopamine neurons during morphine withdrawal syndrome by recording their neuronal activity before and after the administration of low and relatively high doses of clonidine (from 5 to 100 microg/kg). METHODS: The spontaneous neuronal activity of meso-accumbens dopaminergic neurons, identified by antidromical stimulation from the nucleus accumbens, was recorded by use of in vivo extracellular single-unit recordings in control and morphine-withdrawn rats after chronic administration (15 days). RESULTS: Control rats showed a mean spontaneous firing frequency of 2.47+/-0.48 Hz, percentage of burst firing of 22+/-12 and an increase in firing after the administration of cumulative doses of clonidine (5, 10, 20, 40, 100 microg/kg). Conversely, both spontaneous firing rate (1.55+/-0.25 Hz) and the percentage of burst firing (5+/-2) were found to be significantly reduced in rats abstinent for 24 h, and increasing doses of clonidine did not re-establish electrophysiological activity observed in the controls. CONCLUSION: The results indicate that: 1) clonidine did not restore the decreased firing activity of DA neurons in morphine-withdrawn rats, and 2) high doses of clonidine increased firing in control rats but not in morphine-withdrawn rats.

Action Potentials↗
PubMed2001

Magnetic resonance imaging and 1H-magnetic resonance spectroscopy in amyotrophic lateral sclerosis.

We aimed to increase confidence in the combined use of MRI and proton MR spectroscopy (1H-MRS) in diagnosis of amyotrophic lateral sclerosis (ALS). We investigated 12 patients with ALS, seven definite and five probable, taking into account clinical measures of motor neuron function. On T2-weighted images we found high signal in the corticospinal tract in six and low signal in the primary motor cortex in seven of the 12 patients. Atrophy of the precentral gyrus was apparent in all the patients apart from one with probable ALS. Absolute quantification of cerebral metabolites using 1H-MRS demonstrated a significantly lower mean concentration of N-acetylaspartate (NAA) in the precentral gyrus of patients with probable and definite ALS (8.5 +/- 0.62) than in control subjects (10.4 +/- 0.71; P < 0.001). NAA concentration in primary motor cortex correlated with Norris scale scores (r = 0.30; P < 0.0001) but not with the ALS Functional Rating Scale score or disease duration. Significantly lower levels of NAA were detected in patients with low signal in the motor cortex than in those without (P < 0.01). Mean choline (Cho) and creatine (Cr) values did not differ between patients with ALS and controls.

Aged↗
PubMed2001

The costs of childhood epilepsy in Italy: comparative findings from three health care settings.

PURPOSE: To determine the direct costs of epilepsy in a child neurology referral population, stratified by disease, duration, and severity, comparing three different health care settings [i.e., teaching or clinical research (CR) hospitals, general hospitals, and outpatient services]. METHODS: Patients were accepted if they had confirmed epilepsy and were resident in the center catchment area. Eligible subjects were grouped in the following categories: (a) newly diagnosed patients; (b) patients with epilepsy in remission; (c) patients with active non-drug-resistant epilepsy; and (d) those with drug-resistant epilepsy. Over a 12-month period, data regarding the consuming of all resources (i.e., consultations, tests, hospital admissions, drugs), were collected for each patient. Using the Italian National Health Service tariffs, the unit cost of each resource was calculated and indicated in Euros, the European currency. RESULTS: A total of 189 patients was enrolled by two teaching-CR hospitals, two general hospitals, and two outpatient services. The patients were evenly distributed across the four categories of epilepsy. The mean annual cost per person with epilepsy was 1,767 Euros. Drug-resistant epilepsy was the most expensive category (3,268 Euros) followed by newly diagnosed epilepsy (1,907 Euros), active non-drug-resistant epilepsy (1,112 Euros), and epilepsy in remission (844 Euros). Costs were generally highest in teaching-CR hospitals and lowest in outpatient services. Hospital services were the major cost in all epilepsy groups, followed by drugs. CONCLUSIONS: The cost of epilepsy in children and adolescents in Italy tends to vary significantly depending on the severity and duration of the disease Hospitals services and drugs are the major sources of costs. The setting of health care plays a significant role in the variation of the costs, even for patients in the same category of epilepsy.

Adolescent↗
PubMed2001

Modifications of the serotonergic system in mice lacking serotonin transporters: an in vivo electrophysiological study.

The serotonin transporter (5-HTT) plays a key role in the regulation of serotonin (5-hydroxytryptamine, 5-HT) transmission in the pathophysiology and therapeutics of several psychiatric disorders. The mean spontaneous firing rate of midbrain dorsal raphe 5-HT neurons was recorded in chloral hydrate-anesthetized mice. The serotonin transporter (5-HTT), which plays a key role in the regulation of serotonin was significantly decreased in homozygous mice lacking the 5-HT transporter (5-HTT -/-) by 66% and in heterozygous (5-HTT +/-) mice by 36% compared with their normal littermates (5-HTT +/+). Systemic injection of the selective 5-HT(1A) receptor antagonist WAY 100635 enhanced 5-HT neuronal firing by 127% in 5-HT -/- mice, thus indicating an enhanced synaptic availability of 5-HT at inhibitory 5-HT(1A) receptors. Nevertheless, the cell body 5-HT(1A) autoreceptors were desensitized in both 5-HTT -/- and 5-HTT +/- mice. At the postsynaptic level, the recovery time (RT(50)) of the firing rate of hippocampus CA(3) pyramidal neurons following iontophoretic applications of 5-HT was significantly prolonged only in 5-HTT -/- mice. The selective 5-HT reuptake inhibitor paroxetine significantly prolonged the RT(50) in 5-HTT +/+ and 5-HTT +/- mice, without altering the maximal inhibitory effect of 5-HT. These neurons in 5-HTT -/- mice showed an attenuated response to the 5-HT(1A) agonist 8-hydroxy-2-diproplyaminotetralin, but not to 5-HT itself. These results establish that the lack of 5-HTT causes a prolonged recovery of firing activity following 5-HT applications. The genetic deletion of the 5-HTT plays a key role on 5-HT(1A) receptor adaptation: a desensitization at pre- and postsynaptic levels in 5-HTT -/- mice, but to a different extent, and only at the presynaptic level in the 5-HTT +/- group.

8-Hydroxy-2-(di-n-propylamino)tetralin↗