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Biomedical subjects

R Cecchetti

Publications and source records attributed to R Cecchetti.

At least 19 recordsLinked to original sources

Different antioxidant profiles in Italian centenarians: the Sardinian peculiarity.

In this study, 153 Italian centenarians from four different geographical areas, including Modena (northern Italy), Ancona (central Italy), Perugia (central Italy) and Sardinia island (AKEA Project) were enrolled. Plasma levels of vitamin C, uric acid, vitamin A and vitamin E as well as the activities of superoxide dismutase and glutathione peroxidase were measured. Subjects were compared to a younger control population of the same areas, divided into three age groups: <or=60; 61-80 and 81-99 years. The main result of this study is that, whereas in Italian population elevated levels of plasma vitamins A and E seem to be important for longevity, this do not apply to centenarians from Sardinia, in which probably other factors play a more important role.

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Plasma antioxidants are similarly depleted in mild cognitive impairment and in Alzheimer's disease.

In order to assess peripheral levels and activities of a broad spectrum of non-enzymatic and enzymatic antioxidants in elderly subjects with mild cognitive impairment (MCI) and Alzheimer's disease (AD), plasma levels of water-soluble (Vitamin C and uric acid) and of lipophilic (Vitamin A, Vitamin E and carotenoids including lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha- and beta-carotene) antioxidant micronutrients as well as activities of plasma and red blood cell (RBC) superoxide dismutase (SOD) and of plasma glutathione peroxidase (GPx) were measured in 25 patients with MCI, 63 AD patients and 53 controls. Peripheral levels and activities of antioxidants were similarly lower in MCI and AD patients as compared to controls. As MCI may represent a prodromal stage of AD, and oxidative damage appears to occur as one of the earliest pathophysiological events in AD, an increased intake of antioxidants in patients with MCI could be helpful in lowering the risk of conversion to dementia.

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Plasma antioxidants and longevity: a study on healthy centenarians.

A large body of experimental research indicates that oxidative stress contributes to the processes related to aging and to the pathogenesis of several age-related diseases. Vitamins and antioxidant enzymes have a fundamental role in defending the organism from oxidative stress. To better understand the role of antioxidants in human aging, we measured plasma levels of vitamin C (ascorbic acid), uric acid, vitamin E (alpha-tocopherol), vitamin A (retinol), carotenoids, total thiol groups, and the activity of plasma superoxide dismutase (SOD) and glutathione peroxidase (GPX) as well as the activity of red blood cell (RBC) SOD in 32 healthy centenarians-17 elderly subjects aged 80-99 years, 34 elderly subjects aged 60-79 years, and 24 adults aged less than 60 years. Considering the "noncentenarians" only, we observed a consistent behavior in the antioxidant pattern, with a decrease of the nonenzymatic antioxidants and an increase of the enzymatic antioxidant activities relative to age. Remarkably, centenarians were characterized as having the highest levels of vitamins A and E, whereas the activities of both plasma and RBC SOD, which increase with age, decreased in centenarians. From these results, it is evident that healthy centenarians show a particular profile in which high levels of vitamin A and vitamin E seem to be important in guaranteeing their extreme longevity.

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Antioxidant profile and early outcome in stroke patients.

BACKGROUND AND PURPOSE: Experimental studies provide evidence of an association between ischemic stroke and increased oxidative stress, but data in humans are still limited and controversial. The purpose of this study was to investigate the time course of plasma antioxidant changes in ischemic stroke patients. METHODS: Plasma antioxidants, including water-soluble (vitamin C and uric acid) and lipid-soluble (vitamins A and E) compounds as well as antioxidant enzyme activities in plasma (superoxide dismutase [SOD] and glutathione peroxidase) and erythrocytes (SOD), were measured by high-performance liquid chromatography (antioxidant vitamins) and by spectrophotometry (antioxidant enzymes) in 38 subjects (25 men and 13 women aged 77.2+/-7.9 years) with acute ischemic stroke of recent onset (<24 hours) on admission, after 6 and 24 hours, and on days 3, 5, and 7. Antioxidant levels in patients on admission were compared with those of age- and sex-matched controls. RESULTS: Mean antioxidant levels and activities in patients on admission were lower than those of controls and showed a gradual increase over time. Patients with the worst early outcome (death or functional decline) had higher vitamin A and uric acid plasma levels and lower vitamin C levels and erythrocyte SOD activity than those who remained functionally stable. CONCLUSIONS: These results suggest that the majority of antioxidants are reduced immediately after an acute ischemic stroke, possibly as a consequence of increased oxidative stress. A specific antioxidant profile is associated with a poor early outcome.

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Tau protein in cerebrospinal fluid: a new diagnostic and prognostic marker in Alzheimer disease?

Tau is the main protein of paired helical filaments. It can be detected and measured in cerebrospinal fluid (CSF) and for this reason it has been proposed as a possible in vivo marker of Alzheimer disease (AD). To evaluate the usefulness of CSF tau in the diagnosis of AD we measured it in patients with AD, frontal lobe dementia (FLD), vascular dementia (VD), and in healthy controls by means of a specific enzyme-linked immunosorbent assay test. Individuals with AD had significantly higher tau levels than FLD, VD, and controls. Individuals with late onset AD had significantly higher levels than those with early onset disease. In AD, CSF tau level did not correlate with age, duration, or severity of the disease, whereas a correlation with age was found in FLD and controls. In the nine AD patients in whom CSF tau measurement was repeated after 2 years, mean levels did not differ from baseline, although a worsening of cognitive performances occurred. The overlap among the different groups and the absence of any modification over time suggest that CSF tau measurement, more than in confirming or staging overt AD, might be useful in revealing the disease at its preclinical phase.

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Oxidative damage to DNA in lymphocytes from AD patients.

OBJECTIVE: Several studies show structural and functional alterations in peripheral cells in AD. The purpose of this study was to evaluate oxidative stress in AD lymphocytes. BACKGROUND: The literature supports the role of reactive oxygen species in the pathogenesis of AD because several markers of oxidative damage have been detected in AD brain. METHODS: 8-hydroxy-2'-deoxyguanosine (8OHdG), a marker of oxidative stress in DNA, was measured in lymphocytes of AD patients and healthy aged controls with high-pressure liquid chromatography with electrochemical detection, both at basal condition and after acute oxidative stress with hydrogen peroxide. RESULTS: A significantly higher concentration of 8OHdG in lymphocytes occurred in AD patients compared with controls. In this latter group, 8OHdG increased progressively with age. After acute oxidative stress, levels of formed 8OHdG did not differ between AD patients and controls. CONCLUSIONS: Our results support that AD is affected by oxidative stress, detectable not only in the brain but also in peripheral cells; oxidative mechanisms may contribute to the pathogenesis of AD. Additional studies in other neurodegenerative diseases are needed to evaluate these findings.

8-Hydroxy-2'-Deoxyguanosine↗

Mitochondrial membrane fluidity and oxidative damage to mitochondrial DNA in aged and AD human brain.

Oxidative damage on biological molecules has been proposed as a major cause of alterations observed in aging brain as well as in neurodegenerative diseases. In this study, we measured membrane fluidity in mitochondria extracted from three cerebral regions and cerebellum of Alzheimer disease (AD) patients and age-matched controls by means of fluorescence polarization technique. A significant reduction of mitochondrial membrane fluidity was found in AD, except in cerebellum. In controls, a decrease of membrane fluidity was observed along with age, and it was also related to the content of the oxidized nucleoside 8-hydroxy-2'-deoxyguanosine (OH8dG) in mitochondrial DNA (mtDNA). Alteration in membrane fluidity seems to be a result of lipid peroxidation, since it dramatically decreased when mitochondria were exposed to FeCl2 and H2O2. The parallel increase of viscosity in mitochondrial membrane and the amount of OH8dG in mtDNA is suggestive of a relationship between these biological markers of oxidative stress. These results provide further evidence that oxidative stress may play a role in the pathogenesis of AD.

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Altered mitochondrial membrane fluidity in AD brain.

Oxidative damage on biological membranes has been proposed as a cause of the alterations observed in aging brain and, more severely, in Alzheimer's disease (AD). In this study we evaluated membrane fluidity of mitochondria extracted from different areas of normal and AD brains by means of fluorescence polarization technique. AD mitochondria showed a significant reduction of membrane fluidity compared to controls except in cerebellum. This might be caused by a greater lipid peroxidation of biological membranes, as suggested by in vitro experiments we performed to this purpose. From these results the possible role of oxidative stress in AD pathogenesis is supported.

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Chronic hepatitis C and B-cell non-Hodgkin's lymphoma.

Hepatitis C virus (HCV), a hepatotropic and lymphotropic virus, is the major causative agent of nonA-nonB chronic hepatitis; moreover, it is frequently associated with benign and malignant lymphoproliferative disorders such as mixed cryoglobulinaemia and B-cell non-Hodgkin's lymphoma (NHL). We investigated the clinical and virological features of B-cell NHL complicating chronic hepatitis C in a series of 10 patients (M/F 1/9; mean age 63 +/- 6SD years). The malignancy appeared after median 8 +/- 4SD years from onset and was low-grade in six patients, intermediate in three, and high-grade in one. 'One-tube nested' PCR detected serum HCV RNA and viral ongoing replication in both fresh and cultured peripheral lymphocytes in all ten. Analysis of HCV genotypes showed a relatively higher prevalence of 2a/III type compared with unselected chronic hepatitis C (50% vs. 15%). In one patient, HCV RNA was also found in the neoplastic bone marrow and lymph-node specimens. B-cell NHL can complicate chronic hepatitis C and affect the overall prognosis of the disease. The increasing frequency of chronic hepatitis C worldwide suggests that the actual prevalence of this complication may be underestimated. Careful clinical work-up at diagnosis and during follow-up is particularly recommendable.

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Increased cerebrospinal fluid pyruvate levels in Alzheimer's disease.

Impaired energy metabolism is an early, predominant feature in Alzheimer's disease. In order to find out simple, reliable 'in vivo' markers for the clinical-biological typization of the disorder, we measured cerebrospinal fluid (CSF) glucose, lactate and pyruvate levels in patients suffering from dementia of Alzheimer type (DAT) and in healthy elderly controls. DAT group showed remarkably higher levels of pyruvate (P = 0.01), with no overlap with the values obtained in controls. CSF pyruvate levels were also significantly associated with the severity of dementia. Therefore, CSF pyruvate levels neatly separate DAT patients from controls, having also pathogenetic value.

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Cerebrospinal fluid neuron-specific enolase in Alzheimer's disease and vascular dementia.

Levels of neuron-specific enolase (NSE), a glycolytic enzyme localized in neurons, were measured in serum and cerebrospinal fluid (CSF) of patients with early-onset (e-AD) and late-onset (l-AD) Alzheimer's disease, vascular dementia (VD) and controls. Mean CSF NSE levels in patients with Alzheimer's disease did not significantly differ from those in controls, although in the AD group a correlation was found between NSE levels and severity of cognitive deficits. In VD patients, CSF NSE was lower than in controls or in AD patients. These findings are of physiopathological interest but suggest that CSF NSE is not a useful biological marker in dementia disorders.

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Serum anti-GFAP and anti-S100 autoantibodies in brain aging, Alzheimer's disease and vascular dementia.

Autoantibodies against glial fibrillary acidic protein (GFAP) and S100 protein were measured in sera of patients suffering from vascular dementia (VD), presenile Alzheimer's disease (AD), senile Alzheimer's disease (SDAT) and aged healthy controls by means of ELISA test. VD and SDAT showed the highest levels of both autoantibodies, AD the lowest. From these results a relationship between autoantibody titers and aging seems possible. Dosage of anti-GFAP and anti-S100 autoantibodies does not appear useful for diagnostic purpose because of the overlap observed among groups. Rather, the presence of these antibodies seems to reflect an alteration of the blood-brain barrier that promotes the access of central nervous system antigens to immunocompetent cells.

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Platelet MAO-B activity as a marker of behavioural characteristics in dementia disorders.

Both low and high platelet MAO-B (pMAO-B) activity is considered an indicator of increased vulnerability in psychopathology. How the activity of this peripheral enzyme can be linked with the sophisticated functions of the central nervous system (CNS) is not clear; in man, evidence exists that the genetic mechanisms determining the size or capacity of the central serotonin system are common to platelet and brain MAO. In the present study pMAO-B activity was evaluated in demented patients suffering from early-onset Alzheimer's disease (AD), late-onset Alzheimer's disease (SDAT), vascular dementia (VD), and controls. In these dementia categories, the relationship between pMAO-B activity and clinical features, and between pMAO-B activity and cerebrospinal fluid (CSF) monoamine metabolites (3-methoxy-4-hydroxyphenyl-glycol, MHPG; 5-hydroxy-indoleacetic acid, 5-HIAA; homovanillic acid, HVA) was also investigated. pMAO-B activity was significantly higher in SDAT patients, compared to controls and AD. Age, as covariate, failed to show any significant effect, and no association was found between pMAO-B activity and CSF monoamine metabolites. The correlation analysis between pMAO-B and neuropsychological scores showed a highly significant positive relationship with GBS-emotional impairment (N = 40, r = 0.72, p < 0.01) in the SDAT group. This result suggests the importance of platelet MAO-B activity as biological marker also in old-age dementias, namely senile dementia of Alzheimer type, where the increased activity of this enzyme might constitute a marker for vulnerability toward behavioural disturbance, i.e., emotional deterioration.

Affective Symptoms↗