Lodovico Frattola

Sensory impairment and quality of life in a community elderly population

Objective: To determine the association between quality of life measures and sensory impairment in aged individuals living at home.

Clinical, neuropsychological, and morphometric correlates of apathy in Parkinson's disease

Apathy is a salient feature of various neuropsychiatric disorders, from depression to Alzheimers disease. We formally assess its prevalence in idiopathic Parkinsons disease (PD) together with its clinical, neuropsychological, and morphometric correlates. Thirty patients with PD and 25 normal controls were assessed using an extensive neuropsychological battery and Marins Apathy Scale; parkinsonian patients also underwent MRI scan, followed by linear measurement of various frontotemporal structures. Approximately 45% of the PD sample showed apathy. For comparison analysis, given the unimodal distribution of the apathy scores, the PD sample was divided into three groups on the basis of the apathy tertiles. All three PD groups had worse cognitive and depression scores than controls, whereas they did not differ in terms of demographic, neurological, general cognitive, or affective features. By contrast, a significant positive association was found between apathy scores and performance on tests of executive function. As regards the morphometric data, we failed to find any specific measure of frontotemporal atrophy correlating with the presence or severity of apathy. Thus, apathy seems to be a frequent and important companion of PD, in many cases probably due to a primary motivational impairment, possibly related to a frontosubcortical dysfunction.

Increased cytokine release from peripheral blood cells after acute stroke

Cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α 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-α 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-α 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-α 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 hemorragic 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-α production in peripheral blood cells, which are a major source of serum cytokines after stroke.

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.

Decreased density of benzodiazepine receptors in lymphocytes of anxious patients: reversal after chronic diazepam treatment

Peripheral‐type benzodiazepine receptors were measured in human circulating lymphocytes using 3H‐PK 11195 as specific ligand. In a group of outpatients with anxiety disorders a significant decrease of receptor density (– 37%) was found compared with age‐matched controls. In these patients long‐term diazepam treatment restored binding density to normal levels: the effect persisted after drug withdrawal. Acute i.v. diazepam administration did not change receptor density. The observed receptor changes could reflect a down‐regulation phenomenon and indicate that lymphocyte function reflect central nervous events.

Carboplatin toxic effects on the peripheral nervous system of the rat

BACKGROUND The most striking of carboplatins 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.

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.

Glutamate transporters in platelets: EAAT1 decrease in aging and in Alzheimer's disease

Platelets release glutamate upon activation and are an important clearance system of the amino acid from blood, through high-affinity glutamate uptake, similar to that described in brain synaptosomes. Since platelet glutamate uptake is decreased in neurodegenerative disorders, we performed a morphological and molecular characterization of platelet glutamate transporters. The three major brain glutamate transporters EAAT1, EAAT2 and EAAT3 are expressed in platelets, with similar molecular weight, although at lower density than brain. A Na(+)-dependent-high-affinity glutamate uptake was competitively inhibited by known inhibitors but not by dihydrokainic acid, suggesting platelet EAAT2 does not play a major role in glutamate uptake at physiological conditions. We observed decreased glutamate uptake V(max), without modification of transporter affinity, in aging, which could be linked to the selective decrease of EAAT1 expression and mRNA. Moreover, in AD patients we found a further EAAT1 reduction compared to age-matched controls, which could explain the decrease of platelet uptake previously described. Platelet glutamate transporters may be used as peripheral markers to investigate the role of glutamate in patients with neuropsychiatric disorders.

Glutamate uptake is decreased in platelets from Alzheimer's disease patients

Because excitotoxicity may be involved in neurodegeneration in Alzheimers disease, we investigated possible modifications of platelet glutamate uptake in AD patients. High‐affinity glutamate uptake was studied in platelets from 35 Alzheimers disease patients, 10 multi‐infarct dementia patients, and 35 age‐matched normal controls; it was decreased by 40% in platelets from Alzheimers disease patients compared with controls and with multi‐infarct dementia patients. Platelet glutamate uptake could be used as peripheral marker of glutamatergic involvement and as adjunctive diagnostic tool in Alzheimers disease patients. Ann Neurol 2000;47:641–643

Benzodiazepine receptors and diazepam binding inhibitor: A possible link between stress, anxiety and the immune system

This review summarizes the evidence available on the involvement in stress of different classes of benzodiazepine receptors and their putative endogenous ligand, diazepam binding inhibitor (DBI), with particular reference to their role in modifications of the immune response. The presented data from in vitro, experimental, and clinical studies suggest that benzodiazepine receptors and DBI play a major role in regulating steroid production in both the adrenals and central nervous system, and may be involved in the activation of the hypothalamic-pituitary-adrenal axis in stress response.