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Biomedical subjects

G Binetti

Publications and source records attributed to G Binetti.

At least 55 records · Page 3Linked to original sources
PubMed1997

Effect of energy shortage and oxidative stress on amyloid precursor protein metabolism in COS cells.

The present study investigates the influence of energy related metabolic stress on amyloid precursor protein (APP) non-amyloidogenic secretory processing in COS cells. The effect of glucose deprivation on soluble APP (sAPP) secretion has been evaluated: incubation of COS cells with 50 mM 2-deoxy-D-glucose (2-DG) in glucose free medium was able to reduce sAPP secretion (-26%). Sodium azide (NaN3), an inhibitor of cytochrome c oxidase (complex IV of the mitochondrial electron transfer chain) decreased sAPP release in a concentration dependent way (maximum -75%). Treatment of COS cells with the antioxidant glutathione (GSH) fully antagonized the inhibitory effect of azide (1 mM) and elicited sAPP release over basal level. These results suggest that the inhibition of energy metabolism can influence APP processing leading to a decreased secretion of non-amyloidogenic fragments of APP.

Amyloid beta-Protein Precursor↗
PubMed1997

Procedural memory stimulation in Alzheimer's disease: impact of a training programme.

The study evaluates the efficacy of a procedural memory stimulation programme in mild and mild-moderate Alzheimer's disease (AD). Twenty basic and instrumental activities of daily living have been selected, and divided into two groups, comparable for difficulty. Ten normal elderly subjects (age 68.0 +/- 4.8 years; MMSE score: 28.7 +/- 0.9; education: 7.6 +/- 3.5 years) were asked to perform the two groups of daily activities and the time required to perform the tasks of each group was recorded and used as a reference. Ten mild and mild-moderate AD patients (age 77.2 +/- 5.3 years; MMSE score: 19.8 +/- 3.5; education: 7.3 +/- 4.7 years) without major behavioural disturbances constituted the experimental group. Patients were evaluated in all 20 daily activities and the time employed was recorded at baseline and after a 3-week training (1 h/d, 5 d/week) period. Five patients were trained during the 3 weeks on half of the 20 daily activities and the other five patients were trained on the remainder. This procedure was adopted in order to detect separately the improvement in "trained" and "not trained" activities, allowing to control better the effects of the intervention. The assessment of the functional impact of the training was directly measured, through the variation of time employed to perform tasks before and after training. After 3 weeks of training a significant improvement was observed for the trained activities, from 3.6 to 1.9 standard deviations below the performance of the normal elderly controls (P < 0.05). AD patients improved also in not-trained activities from 3.5 to 2.7 standard deviations below the controls' performance (P < 0.05). The rehabilitation of activities of daily living through developing procedural memory strategies may be effective in mild and mild-moderate AD patients.

Activities of Daily Living↗
PubMed1996

Disorders of visual and spatial perception in the early stage of Alzheimer's disease.

A battery of visual and spatial perception tests (VOSP) has been administered to a sample of 25 mild Alzheimer's disease (AD) patients and 25 age- and education-matched controls in order to assess visuospatial skills in the early phase of the disease. Among visual object perception tests, AD patients were impaired only in the task where they had to name the stimulus (Silhouettes task). The score in this task significantly correlated with the Boston Naming Test score (r = .73; p < 0.0001). The performance on the Object decision task (which does not require naming), figure-ground analysis, and identification of degraded stimuli was unimpaired. Similarly there were no significant differences for any of the spatial perception tests. The results showing that the performances on most measures of visual and spatial perception is unimpaired, indicate that the "early" perceptual processes, as well as the access to structural knowledge, are not defective in early AD. On the other hand, AD patients are impaired at the level of semantic access and name retrieval. The finding of an highly significant correlation among tests requiring visual access to structural and semantic knowledge suggests that a rigid separation between perceptual and semantic mechanisms may be unwarranted.

Aged↗
PubMed1996

Defective protein kinase C alpha leads to impaired secretion of soluble beta-amyloid precursor protein from Alzheimer's disease fibroblasts.

The present study shows that cultured fibroblasts from sporadic AD patients present: a) reduced (-30%) cytosolic protein kinase C (PKC) activity; b) increased KD of phorbol ester binding (+94%) in cytosolic fractions; c) reduced (-30%) soluble protein kinase C alpha immunoreactivity; d) lower (-27.5%) basal soluble APP secretion and e) reduced soluble APP secretion in response to low phorbol ester concentrations (over threefold difference using 9 nM phorbol-12,13-dibutyrate-PdBu). Since the PKC-stimulated secretion of APP leads to the cleavage of the precursor within the amyloidogenic beta-A4 fragment, the reduced PKC activity in AD patients may lead to accumulation of potentially amyloidogenic or toxic APP fragments. A defect in the secretion of soluble amyloid beta-protein precursor is indeed suggested by literature data on familial AD fibroblasts as well as by the reported results.

Alzheimer Disease↗
PubMed1996

Medical treatment of end-stage heart failure.

Congestive heart failure is a lethal condition that affects an increasing number of patients. In recent years a great amount of data have accumulated on the pathophysiology and medical and surgical therapy of this condition. In spite of the advances in its management and the great number of patients affected, common errors are still made by internists and cardiologists in the use of drugs and therapeutic strategies. Digitalis has only recently been shown to affect hemodynamics, exercise capacity, and clinical symptoms, but the effects on survival still have to be demonstrated. Loop diuretics, eventually combined with thiazides and antialdosterone drugs in patients with clinical signs and symptoms of fluid retention, are the mainstays of therapy of congestive heart failure. In order to make diuretic therapy efficacious, moderate salt and water intake restriction is mandatory. Angiotensin-converting enzyme (ACE) inhibitors are now considered unavoidable drugs in the management of heart failure, and an attempt to reach the doses that have been shown to be efficacious for survival in the large trials has to be made in every patient with this condition. Other vasodilators, such as hydralazine and nitrates, which show a less pronounced effect on survival but more effective hemodynamic actions than ACE inhibitors, may be used to control mitral insufficiency or to improve hemodynamics in very sick patients. Hemodynamic instability refractory to increasing doses of vasodilators and diuretics is a severe condition that requires hospital admission to administer drugs parenterally. These patients are usually treated with the combination of catecholamines and phosphodiesterase inhibitors associated with intravenous diuretics until clinical stability is again achieved and oral therapy is resumed and restructured. The use of aggressive pharmacological therapy and phosphodiesterase inhibitors has reduced the need for assisted circulatory support in these patients. Beta-blockers have shown promising results when administered to patients with heart failure, although a definitive demonstration of their effects on survival is still lacking. Other additional measures that need to be considered in patients with end-stage congestive heart failure are the use of antiarrhythmic drugs and anticoagulation.

Adrenergic beta-Antagonists↗
PubMed1996

The Mini-Mental State Examination in Alzheimer's disease and multi-infarct dementia.

The aim of this study was to compare the performances on each item of the Mini-Mental State Examination (MMSE) of patients with Alzheimer's disease (AD) and multi-infarct dementia (MID). In order to identify the items that could better distinguish the two groups of patients, 70 AD and 31 MID patients matched for disease severity, age, and education were evaluated. The scores of the 101 patients on each of the MMSE items were entered into a principal component factor analysis using varimax rotation, and two main components were derived. Component 1 was probably representative of recently acquired information, whereas component 2 represented educational level. A score summing the items that loaded on component 1 and the recall item was calculated to generate a measure of episodic memory. Performing analysis of variance and covarying for age and education revealed that this score was statistically different in the two groups, with AD patients having lower values. The data suggest that the MMSE may demonstrate a pattern of impairment of memory that differs between AD and MID. Possible explanations of this finding should take into account the different neuroanatomical impairments and the different degrees of motivation, due to depression or attentional deficits, toward external stimuli.

Aged↗
PubMed1996

Neuropsychiatric Syndromes in Neurodegenerative Disease: Frequency and Signficance.

Neurodegenerative diseases have neuropsychological, neuropsychiatric, and neurological effects manifested as cognitive, emotional, and physical alterations. These primary effects have secondary consequences on activities of daily living, patient and caregiver distress, and quality of life. Neuropsychiatric manifestations are products of brain dysfunction that are associated with institutionalization, vulnerability to abuse by the caregiver, and use of medications and restraints. Behavioral alterations can often be ameliorated by psychotropic drugs, and the effects of medications contribute to understanding the mechanisms of behavioral changes. Allocation of health service resources for dementia patients is partially determined by the neuropsychiatric dimension of these diseases, and the importance of the neuropsychiatric aspects of degenerative disorders has been underemphasized.

Journal Article↗
PubMed1996

Executive dysfunction in early Alzheimer's disease.

Twenty five patients with probable mild Alzheimer's disease were assessed for deficits in executive functioning and the impact of these deficits on performance in other neuropsychological domains. The Wisconsin card sorting test, the release from proactive interference paradigm, the verbal fluency test, and the Stroop test were adopted to classify patients with (AD+) and without (AD-) executive deficits. Seven of the patients showed an impairment in executive function (AD+), defined as a performance below the cut off score in at least two of these tests. There were no significant differences in clinical assessments, demographic features, or other cognitive functions between patients. Executive dysfunction may be an early additional feature in a subgroup of patients with mild Alzheimer's disease. Impairment on frontal lobe tests does not seem to be related to the severity or duration of disease, or to a different pattern of impairment in other cognitive domains.

Aged↗
PubMed1996

Risk of mortality and institutionalization in demented patients with delusions.

Delusions are a common symptom during the course of dementia. Despite their clinical relevance, however, it is still unclear whether they are of prognostic value. This longitudinal study involving, at baseline, 99 demented Alzheimer disease (AD) and multi-infarct dementia (MID) patients, investigates the risk of mortality and institutionalization at 2 years after discharge from a dementia unit in patients with and without delusions at baseline. Results indicate that the presence of delusions is a significant predictor of future institutionalization (odds ratio 3.6, confidence interval 1.3-9.6), even when confounding factors such as age, educational level, and severity of cognitive and functional impairment are statistically controlled. No significant impact on survival was found.

Aged↗
PubMed1996

Fibroblasts of patients affected by Down's syndrome oversecrete amyloid precursor protein and are hyporesponsive to protein kinase C stimulation.

The present study investigates the ability of the pharmacologic activation of protein kinase C (PKC) to modulate amyloid precursor protein (APP) secretion in human skin fibroblasts from patients affected by Down's syndrome (DS). We assessed DS subjects at the Hospital Institute of Sospiro, Cremona, and at the Alzheimer's Disease Unit of the Sacred Heart Hospital in Brescia, and we subdivided them into nondemented (NDS) and demented (DDS) patients. All DS patients were trisomy 21 karyotype. DS fibroblasts had an increased content of APP immunoreactive material as revealed by immunocytochemistry analysis. The basal secretion of soluble APP was higher (+94.6%) in Down's cells with respect to controls. The observation on the fibroblasts prepared from DS is consistent with these patients' possessing an extra copy of the APP gene (mapped on chromosome 21) leading to increased APP expression. Phorbol-12,13-dibutyrate (PdBu, 9 to 150 nM) treatment promoted a dose-dependent increase of secreted APP in the conditioned medium of control fibroblasts. The peak response (+102.2%) was attained using 150 nM PdBu. In Down's fibroblasts, PdBu stimulated APP secretion already maximally at low concentrations (9 nM), but the peak response, due to the higher basal release, was lower on a percentage basis (+16.4%) than in control fibroblasts. The results indicate that in Down's fibroblasts the mechanisms controlling APP release are at least quantitatively altered. In addition, these results suggest caution when using information obtained from Down's patients to model Alzheimer's disease biochemical defects.

Adult↗
PubMed1995

Defective phorbol ester-stimulated secretion of beta-amyloid precursor protein from Alzheimer's disease fibroblasts.

The present study shows that cultured fibroblasts from sporadic Alzheimer's disease patients are deficient in protein kinase C-regulated secretion of amyloid precursor protein. In particular, Alzheimer fibroblasts show a reduced basal secretion and a reduced response at low concentrations of phorbol-12,13-dibutyrate, with an EC50 twofold higher than control fibroblasts. Furthermore, we observed that such defective regulation of the amyloid precursor secretion can possibly be correlated to a specific defect in protein kinase C alpha in fibroblasts from Alzheimer patients.

Aged↗
PubMed1995

Release from proactive interference in early Alzheimer's disease.

The study analyses the performance of 22 mild Alzheimer's disease (AD) patients on the Release from Proactive Interference (RPI) paradigm with the aim to investigate the relationship of RPI with frontal function. Twenty-one normal elderly subjects, age and education matched, constituted the control group. Patients with AD were found to recall less words on each trial of the RPI than did the controls. The analysis of Proactive Interference (PI) and Release from PI, in AD patients, by using Anova (trial x group), showed a significant effect of trial and group but not a group by trial interaction. These results indicate a similarity between the performance of AD patients and normal controls on the Release from Proactive Interference paradigm. Despite the similar pattern of performance, AD patients were significantly inferior to normal controls with regard to global performance level. The AD patients' scores on "frontal lobe" tests were correlated with an index of RPI (shift condition index). The only significant result was with the number of categories on the Wisconsin Card Sorting Test, suggesting a weak correlation between RPI and "frontal lobe" function.

Aged↗
PubMed1995

Semantic memory in Alzheimer's disease: an analysis of category fluency.

In order to study the strategies of access to semantic knowledge and the status of semantic representation, we analyzed the performance in a semantic fluency task (Animal naming) of 70 patients with probable Alzheimer's disease (AD), including 40 mild AD patients and 30 moderate-severe AD patients, and 35 matched elderly normal control subjects. The total amount of words produced, their lexical frequency, the number and type of errors, as well as the presence and the type of clusters of related animal names were recorded. AD patients produced less animal exemplars than controls. In addition to a lower total number of clusters, the AD patients showed a strong limitation in clusters' selection, producing a limited number of different clusters. While normal subjects produced several different clusters, only farm animals were clustered by AD patients. When the total amount of words was considered, the mean lexical frequency was higher in the AD group. On the other hand, the words produced within clusters were comparable to terms of lexical frequency and number. These data confirm the impairment of AD patients in category fluency tasks, and suggest a degradation of semantic knowledge as the most likely underlying mechanism.

Aged↗
PubMed1995

Delusions and dementia: clinical and CT correlates.

INTRODUCTION: Delusions occur frequently during the course of Alzheimer's disease (AD) and multi-infarct dementia (MID). Their clinical significance and their relationship with progression of disease and involvement of selected cerebral areas are still unclear. The aim of the study was to determine the clinical and CT correlates of delusions in patients with dementia. MATERIAL AND METHODS: A series of 67 probable AD and 32 MID patients, underwent computed tomographic scans, psychometric tests, neurologic and psychiatric examination, and blood and serum tests. RESULTS: Twenty-four patients were found to have delusions during the clinical evaluation. Delusional patients showed a significantly higher age when compared with non-delusional patients. The results of a multiple logistic regression (with stepwise deletion of the redundant variables) of the CT lesions on the presence of delusions, showed that only the presence of isolated white matter lesions in the frontal lobes were significantly related to the occurrence of delusions (Exp B = 3.42; Beta = 1.2; S.E. = 0.6; Sig T = 0.04). Frontal white matter changes were significantly related to delusions when a multiple regression analysis, entering age and total number of lesions at CT scans, was carried out. CONCLUSIONS: We found that focal lesions in the frontal areas were the only variable that appeared to be significantly and independently associated with delusional disorders.

Activities of Daily Living↗
PubMed1995

Computed tomography in the detection of the vascular component in dementia.

We evaluated the presence and type of vascular lesions with computerized tomography (CT) in 94 cognitively impaired elderly patients who had been defined as degenerative (Alzheimer's disease, AD) or vascular (multi-infarct dementia, MID) dementia patients on the basis of clinical data. Twenty-six percent of the 77 AD, but only 59% of the 17 MID patients had vascular lesions. The most represented vascular lesions were leukoaraiosis in AD and hemispherical cortical lesions in MID patients. Age, signs indicative of, and risk factors for vascular disease were associated with vascular lesions on CT. We conclude that CT scan is a necessary complement to historical and clinical data in the detection of vascularity in demented patients.

Aged↗