PubMed Health⌕ Search

Biomedical subjects

L Tremolizzo

Publications and source records attributed to L Tremolizzo.

17 recordsLinked to original sources
PubMed2007

Third cranial nerve palsy? Look for a sicca syndrome.

Sjogren's syndrome (SS) is a systemic autoimmune disorder, and neurological involvement may frequently occur. Here we describe a 79-year-old woman who came to our attention for a sudden right incomplete 3rd cranial nerve palsy. Following extensive investigations, a diagnosis of primary SS was reached, and the patient recovered after treatment with ev Ig and steroids. Therefore, we suggest that SS should be considered in apparently idiopathic 3rd cranial nerve palsies, since, with the appropriate treatment, they might be transient and reversible.

Aged↗
PubMed2007

Platelet glutamate uptake and release in migraine with and without aura.

Glutamate may play an important role in the pathogenesis of migraine: glutamate release in the brain may be involved in the development of spreading depression and increased concentrations of this amino acid have been reported in plasma and platelets from migraine patients. Here we assessed platelet glutamate uptake and release in 25 patients affected by migraine with aura (MA) and 25 patients affected by migraine without aura (MoA), comparing the results with a group of 20 healthy matched controls. Both glutamate release from stimulated platelets and plasma concentrations of the amino acid were assessed by high-performance liquid chromatography, and were increased in both types of migraine, although more markedly in MA. Platelet glutamate uptake, assessed as 3H-glutamate intake, was increased in MA, while it was reduced in MoA with respect to the control group. These results support the view that MA might involve different pathophysiological mechanisms from MoA and, specifically, up-regulation of the glutamatergic metabolism. Understanding these dysfunctional pathways could lead to new, possibly more successful therapeutic approaches to the management of migraine.

Adolescent↗
PubMed2006

Human platelets express the synaptic markers VGLUT1 and 2 and release glutamate following aggregation.

Vesicular glutamate transporters (VGLUTs) are involved in storing glutamate for secretion at the level of glutamatergic axon terminals, and for this reason they have been extensively used as markers to identify glutamate-releasing cells. Platelets have been considered as a suitable model for studying glutamatergic dysfunction because they perform glutamate uptake and express both external transporters, and NMDA-like receptors. Here, we show that platelets express the pre-synaptic markers VGLUT1 and VGLUT2 and release glutamate following aggregation, implying a possible contributory role in the pathophysiology of stroke, migraine, and other excitotoxic disorders.

Adult↗
PubMed2006

Vitamin E intake and quality of life in amyotrophic lateral sclerosis patients: a follow-up case series study.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder involving both upper and lower motor neurons, leading inexorably to death within a few years. Although our understanding of the pathogenesis of this disease has grown at a very fast rate in recent years, we do not yet have effective treatment options that can positively impact the quality of life (QoL) of these patients. Interestingly, increasing experimental evidence suggests that oxidative stress is involved in the pathogenesis of ALS and that vitamin E could reduce neuronal damage. Hence, in this observational study we determined the QoL in 33 ALS patients taking or not taking vitamin E supplementation (600 mg/day), using the Italian version of the Short-Form 36-Item Health Survey (SF-36). No differences were seen between the two groups of patients, therefore we do not recommend routine use of vitamin E in ALS patients, at least in the absence of randomised clinical trials specifically designed for addressing this issue.

Aged↗
PubMed2004

MIDAS questionnaire in the emergency setting.

Migraine is a common disorder and is a major cause of disability and loss of working performance in western countries. Therefore, many tools have been developed to assess migraine related disability. Among these, the Migraine Disability Assessment (MIDAS) questionnaire has been shown to be of particular interest, as it is valid, reliable and useful for therapeutic decisions. In this pilot study, we address the validity of the MIDAS questionnaire in an unselected population of migraine patients in the emergency setting. We found that the MIDAS scores in the emergency room were similar to those collected in a specialised headache centre. This result suggests that the MIDAS questionnaire could be reliably used in the emergency setting, hence avoiding unnecessary delays in the treatment of migraine patients.

Adult↗
PubMed2004

Enhanced dizocilpine efficacy in heterozygous reeler mice relates to GABA turnover downregulation.

Reelin synthesized by cortical GABAergic interneurons throughout the telencephalon is secreted into the extracellular matrix (ECM) and binds with nM affinity to integrin receptors located at dendritic spine postsynaptic densities and positively modulates Arc and other dendritic resident mRNAs translation, thereby facilitating the onset of synaptic plasticity and LTP consolidation. Accordingly, the reelin haploinsufficient heterozygous reeler mice (HRM) express a marked decrease of cortical thickness, of cortical and hippocampal dendritic spine density, and of cortical GAD67 expression. Behaviorally, HRM manifest a sensorimotor deficit, an exaggerated response to fear, and a deficit in olfactory discrimination learning. HRM and wild-type mice (WTM) were trained to retrieve to criterion palatable chocolate-flavored food pellets in an eight-arm radial maze. In 9-14 days of training HRM and WTM learned the task equally well committing only a few errors. However, HRM, when compared with WTM, show a greater cognitive impairment following the administration of dizocilpine. Also, HRM are more susceptible to the increased locomotion and stereotypic behavior elicited by dizolcipine. The enhanced dizocilpine susceptibility of HRM is not due to differences in pharmacokinetics because the levels of dizocilpine in cortices of HRM and WTM were virtually equal. We also failed to detect differences between HRM and WTM in glutamate brain content and in the rate of 13C-glucose incorporation into the glutamate brain pools. In contrast we found that the conversion index of glutamate into GABA (an indirect measurement of GABA turnover rate) is decreased in cortex, hippocampus and striatum of HRM when compared to WTM. Thus, HRM recapitulate several neurochemical and behavioral endophenotypes reminiscent of schizophrenia and these mice can be proposed as a relevant animal model for the study of pharmacological treatments aimed at alleviating the sensory-motor and cognitive dysregulation associated with schizophrenia.

Animals↗
PubMed2004

A GABAergic cortical deficit dominates schizophrenia pathophysiology.

Several lines of evidence support the role of an epigenetic-induced GABAergic cortical dysfunction in schizophrenia psychopathology, which is probably dependent on an increase in the expression of DNA-methyltransferase-1 occurring selectively in GABAergic neurons. The key enzyme regulating GABA synthesis, termed glutamic acid decarboxylase 67 (GAD67) and the important neurodevelopmental protein called reelin are coexpressed in GABAergic neurons. Upon release, GABA and reelin bind to postsynaptic receptors located in dendrites, somata, or the axon initial segment of pyramidal neurons. Because GAD67 and reelin are downregulated in schizophrenia, it is suggested that schizophrenics may express GABAergic deficit-related alterations of pyramidal neuron function. A reduction of dendritic spines is a finding reported in the prefrontal cortex of schizophrenia patients. Because dendritic spines are innervated by glutamatergic axon terminals, very probably this reduction of dendritic spine expression is translated into a functional deficit of glutamatergic transmission. Plastic modifications of neuronal circuits are probably dependent on GABAergic transmitter tone, and it is likely that GABAergic dysfunction is at the root of synaptic plasticity deficits in schizophrenia. Thus, a possible avenue for the treatment of schizophrenia would be to address this GABAergic functional deficit using positive allosteric modulators of the action of GABA at GABAA receptors. Benzodiazepines (BZ) such as diazepam are effective in treating positive and negative symptoms of schizophrenia, but because they positively modulate GABAA receptors expressing alpha1 subunits, these BZs cause sedation and tolerance. In contrast, imidazenil, a full allosteric modulator of GABAA receptors expressing alpha5 subunits may reduce psychotic symptomatology without producing sedation. Hence, imidazenil should be appropriately studied as a prospective candidate for a pharmacological intervention in schizophrenia.

Animals↗
PubMed2002

An epigenetic mouse model for molecular and behavioral neuropathologies related to schizophrenia vulnerability.

Reelin and glutamic acid decarboxylase (GAD)67 expressed by cortical gamma-aminobutyric acid-ergic interneurons are down-regulated in schizophrenia. Because epidemiological studies of schizophrenia fail to support candidate gene haploinsufficiency of Mendelian origin, we hypothesize that epigenetic mechanisms (i.e., cytosine hypermethylation of CpG islands present in the promoter of these genes) may be responsible for this down-regulation. Protracted l-methionine (6.6 mmolkg for 15 days, twice a day) treatment in mice elicited in brain an increase of S-adenosyl-homocysteine, the processing product of the methyl donor S-adenosyl-methionine, and a marked decrease of reelin and GAD67 mRNAs in both WT and heterozygous reeler mice. This effect of l-methionine was associated with an increase in the number of methylated cytosines in the CpG island of the reelin promoter region. This effect was not observed for GAD65 or neuronal-specific enolase and was not replicated by glycine doses 2-fold greater than those of l-methionine. Prepulse inhibition of startle declined at a faster rate as the prepulsestartle interval increased in mice receiving l-methionine. Valproic acid (2 mmolkg for 15 days, twice a day) reverted l-methionine-induced down-regulation of reelin and GAD67 in both WT and heterozygous reeler mice, suggesting an epigenetic action through the inhibition of histone deacetylases. The same dose of valproate increased acetylation of histone H3 in mouse brain nearly 4-fold. This epigenetic mouse model may be useful in evaluating drug efficacy on schizophrenia vulnerability. Hence the inhibition of histone deacetylases could represent a pharmacological intervention mitigating epigenetically induced vulnerability to schizophrenia in individuals at risk.

Acetylation↗
PubMed2002

REELIN and schizophrenia: a disease at the interface of the genome and the epigenome.

The downregulation of the Reelin gene (RELN) that occurs in schizophrenic brains, which are characterized by pyramidal neurons with shortened dendrites and by reduced expression densities of dendritic spines, may well result from hypermethylation of the RELN promoter. In the adult mammalian brain, gamma-aminoburytic acid-secreting (GABAergic) interneurons release RELN into the extracellular matrix, where it binds with high affinity to the integrin receptors present at dendritic spine postsynaptic densities and likely plays a role, elaborated in this article, in synaptic plasticity. In heterozygous reeler mice, which are haploinsufficient in RELN, inhibitors of histone deacetylase increase DNA demethylase activity and restore RELN expression. Such inhibitors could thus be of therapeutic value in mitigating vulnerability to schizophrenia among high-risk individuals.

Animals↗
PubMed2001

Increased glutamate in CSF and plasma of patients with HIV dementia.

BACKGROUND: Experimental evidence suggests that excitotoxicity might play a major role in HIV-induced neurodegeneration. However, few studies have investigated the role of endogenous glutamate in patients with HIV dementia. OBJECTIVE: To analyze CSF and plasma glutamate levels in 30 patients with AIDS with different dementia severity compared with 10 patients with other neurologic disorders, 11 healthy control subjects, and 10 patients with Alzheimer-type dementia. METHODS: CSF and plasma glutamate levels were measured by reverse-phase high-performance liquid chromatography followed by fluorometric analysis. RESULTS: Glutamate CSF levels were increased fivefold in the patients with HIV vs normal control subjects (p = 0.001), patients with Alzheimer-type dementia (p < 0.0001), and patients with other neurologic disorders (p < 0.01). CSF glutamate levels were also related to the degree of dementia (p < 0.02) and brain atrophy (p < 0.002). Plasma levels were also higher in the patients with HIV (p < 0.0001) but did not correlate with either clinical or imaging features. CONCLUSION: Increased CSF glutamate may originate within the CNS and may play a pathogenetic role in HIV dementia, thus supporting the treatment of these patients with glutamate receptor antagonists.

AIDS Dementia Complex↗
PubMed2001

Decreased platelet glutamate uptake in patients with amyotrophic lateral sclerosis.

Decreased glutamate uptake and a loss of the astrocytic glutamate transporter EAAT2 (GLT-1) have been shown in spinal cord and motor cortex of patients with ALS. Because platelets express the three major glutamate transporter subtypes, including GLT-1, and possess a high-affinity glutamate uptake, the authors investigated glutamate uptake in platelets from patients with ALS and controls. A 43% reduction of high-affinity glutamate uptake rate (p < 0.0001) was observed in patients with ALS compared with normal controls and chronic neurologic disorder patients, suggesting a systemic impairment of glutamate uptake in ALS.

Adult↗
PubMed2001

Decreased platelet glutamate uptake and genetic risk factors in patients with Parkinson's disease.

Genetic risk factors seem to play a role in sporadic Parkinson's disease (PD), maybe triggering oxidative stress and excitotoxicity within substantia nigra. However, genetic factors act at systemic level: reduced activity of mitochondrial enzymes and decreased glutamate uptake have been shown in platelets from PD patients. In this study we investigated glutamate uptake in platelets from 38 sporadic PD patients, 13 patients with parkinsonian syndromes and 28 controls and assessed polymorphisms of alpha-synuclein and ApoE genes. A 48% reduction of glutamate uptake p)<0.0001) was observed in PD patients which, with respect to control groups, correlated with the disease severity (r = -0.44, p < 0.05). Genetic studies of this population did not show differences between PD and controls, nor correlations with platelet glutamate uptake.

Apolipoproteins E↗