Biomedical subjects

M Trabucchi

Publications and source records attributed to M Trabucchi.

At least 433 records · Page 24Linked to original sources

PubMedDate not supplied

Age related differences in dopamine-stimulated adenylate cyclase sensitivity to "in vivo" chronic ethanol treatment.

The effect of chronic ethanol consumption on adenylate cyclase activity was measured in striatal membranes derived from aged male rats. The results indicate that the cyclic AMP generating system of old rats has a different sensitivity to ethanol effect compared to the adult animals. In young animals the basal adenylate cyclase activity was enhanced by alcohol consumption while the DA stimulated cyclic AMP production was reduced. In contrast, in 24 months old rats ethanol reduced the basal adenylyl cyclase and enhanced the response to DA indicating a supersensitivity of adenylate cyclase linked DA receptors. This observation was further supported by 3H-Spiperone binding studies. In fact, a higher Bmax was measured in striatal membranes of aged ethanol-dependent rats in comparison to control.

Adenylyl Cyclases↗

PubMedDate not supplied

Chronic ethanol induces changes in opiate receptor function and in met-enkephalin release.

Ethanol induces supersensitivity of striatal delta-opiate receptor sites labelled by 3H-Etorphine. This effect may be ascribed to the diminished enkephalin release detected in striatal slices after chronic ethanol consumption. On the other hand, Kd values for 3H-Met-enkephalin and 3H-DHM (mu-opiate receptors) specific binding are enhanced. The different sensitivity of the two classes of opiate receptors to ethanol may be due to specific effects on enkephalinergic transmission. It has been hypothesized that the decrease of 3H-Met-enkephalin and 3H-DHM affinity for their receptors takes place because endogenous substances from ethanol metabolism (for example salsolinol) behave as mu opioid agonists. This hypothesis is confirmed by "in vitro" studies demonstrating that salsolinol displaces 3H-Met-enkephalin and 3H-DHM but not 3H-DADLE binding. On the contrary, it seems that delta-receptors become supersensitive because of the decreased endogenous peptide release.

Animals↗

PubMedDate not supplied

Chronic ethanol exposure alters dopaminergic signal transduction processes.

A number of data suggest that the chronic ethanol treatment induces derangements of cell membrane structure leading to modifications of membrane related processes. In particular, alterations have been observed in the mechanisms of neurotransmitter recognition and in the coupling of the receptor with the effector system. Phosphorylation of specific proteins by cyclic AMP stimulated protein kinases represent the final step in the biological response in several distinct functional processes. Ethanol neurotoxic action therefore may affect neurotransmitter availability and release as well as receptors effector systems and protein phosphorylation. In this line, chronic ethanol treatment in rats decreases cyclic AMP dependent protein kinase activity in rat striatal membrane fractions. When lysine rich histone type III was used as exogenous substrate, cyclic AMP stimulated 32P incorporation was still decreased in the ethanol group. These data favor the hypothesis of a decreased capability of the enzyme to phosphorylate in response to cAMP.

Alcoholism↗

PubMedDate not supplied

Altered calcium signal transduction after chronic ethanol consumption.

Calcium and calcium-calmodulin dependent phosphorylation of several protein bands was found altered in synaptosomal membranes prepared from ethanol treated rats. The ethanol induced effect on Ca++ and Ca++-calmodulin phosphorylation presented regional differences. In particular 32P incorporation was lower in the striatum and cerebellum, higher in the hippocampus and unmodified in the cortex. Part of the phosphorylated bands had an apparent molecular weight similar to that of the phosphoproteins involved in neurotransmission. These results extend previous observations indicating that calcium movement control is modified during chronic ethanol consumption and suggest that ethanol may interfere at various steps in the calcium-promoted events.

Alcoholism↗

PubMedDate not supplied

Acute ethanol and acetaldehyde administration produce similar effects on L-type calcium channels in rat brain.

The present study investigates the effect of acute ethanol and acetaldehyde administration on neuronal L-type calcium channels by measuring the binding of 3H-nitrendipine (3H-NTP). Acute ethanol (3 g/kg orally) transiently increases (+40% at 40 min) 3H-NTP binding. Acetaldehyde has a similar effect, but the onset of action is shorter; in fact the binding increase peaks 15 min following administration and is completely reversible within 2 hours. Disulfiram pretreatment does not modify the effect produced by acute ethanol on 3H-NTP binding. The results indicate that acetaldehyde may participate in mediating the action of ethanol on voltage sensitive L-type calcium channels with consequent alterations of neuronal excitability.

Acetaldehyde↗

PubMedDate not supplied

Chronic alcohol intake modifies phorbol ester binding in selected rat brain areas.

3H-Phorbol 12,13 dibutyrate binding to rat brain was modified by chronic ethanol treatment. Among the areas examined hippocampus and cortex showed a decrease in Bmax values of 32 and 24% respectively. No significant effect was observed in hypothalamus and cerebellum. In vitro ethanol did not modify the binding in all the areas except at molar concentrations. In hippocampus and cortex the direct measurement of protein kinase C activity indicated that the decrease in phorbol ester binding was accompanied with a concomitant decrease in kinase activity. The results indicate that chronic ethanol treatment leads to an inhibition of brain protein kinase C function.

Animals↗

PubMedDate not supplied

Effects of chronic ethanol intake at a low dose on the rat brain dopaminergic system.

The effects of 8-week ethanol treatment (3% v/v in drinking water) on the rat brain dopaminergic system were investigated. Chronic ethanol consumption induced a significant increase in the number of dopamine D1 receptor sites in the caudate putamen. Conversely, no significant changes were observed in D2 receptor density or affinity. Biochemical results were in agreement with behavioral data, as amphetamine-induced locomotor hyperactivity was significantly higher in ethanol-treated rats in comparison to controls. Moreover, grooming behavior in response to SKF 38393, a selective agonist of D1 receptors was potentiated in ethanol-treated rats, whereas locomotor hyperactivity induced by LY 171555 (a selective agonist of D2 receptors) was not affected by ethanol treatment. The results indicate that changes in dopamine receptors may occur in the central nervous system at levels of ethanol intake that do not induce tolerance or dependence.

Alcohol Drinking↗

PubMedDate not supplied

Alcohol and the brain: setting the benefit/risk balance.

This article reviews the literature and presents some unpublished data on the CNS effects of alcohol at doses not producing tolerance and dependence. The available evidence indicates that the effect of low doses of ethanol may qualitatively differ from those produced in animal models mimicking alcoholism. For example, rats exposed for two months to alcohol in drinking water at a concentration (3%) not inducing tolerance or dependence, as assessed by lack of withdrawal signs upon treatment suspension, appear to be less stressed in the two-way avoidance-learning tests. Accordingly, the treated rats perform better and learn faster than sucrose-fed controls, while this behavior is disrupted by high levels of ethanol intake. These initial observations suggest that discontinuity may exist between the effects of low and high doses of this substance and underscore the need to expand research on the effects of alcohol on the CNS to include the bottom end of the dose-response curve.

Alcoholism↗

PubMedDate not supplied

Assessment of alcohol consumption and alcoholism in the elderly.

This study evaluates characteristics associated with alcohol consumption or alcohol-related problems in an elderly population, as detected by CAGE questionnaire and self-reported alcohol intake respectively. Data were obtained from a multidimensional study carried out in a community-dwelling population aged 70-75 (n = 1205, 389 males and 816 females) living in the city center of Brescia, in northern Italy. All information was gathered by self-report. Male gender, better mood, daily function, somatic health, not living alone, and being married were significantly associated with self-reported alcohol consumption. Male gender, poorer cognitive function, and income dissatisfaction were significantly associated with alcohol problems as detected by CAGE. Data suggest that self-report of alcohol intake, though intrinsically loaded with imperfect internal consistency, does not necessarily indicate risk of alcoholism; on the contrary, it can reveal the positive psychological attitude of the drinking habit. CAGE questionnaire, which is sensitive to alcohol related problems, is associated with poor psychosocial conditions.

Aged↗

PubMedDate not supplied

Neuronal differentiation modifies the effect of ethanol exposure on voltage-dependent calcium channels in NG 108-15 cells.

The effect of prolonged (72 h) ethanol (200 mM) exposure on the labeling of L-type (using tritiated PN 200-110) and N-type (using iodinated omega-conotoxin) voltage-dependent calcium channels was investigated in cultured NG 108-15 cells. In undifferentiated cells ethanol produced an 80% increase in PN 200-110 Bmax and no changes in omega-conotoxin binding. Differentiation had a profound effect on the response of cells to ethanol, which in differentiated neuron-like cells decreased omega-conotoxin binding (-53.5%) leaving PN 200-110 labeling of L-type channels unaffected. The effect was time dependent and reversible upon ethanol withdrawal. The decreased omega-conotoxin binding was accompanied by a reduced ability of omega-conotoxin to inhibit K+ -stimulated calcium uptake. The results demonstrate that in cultured NG 108-15 cells ethanol differentially affects DHP and omega-conotoxin-sensitive, voltage-dependent calcium channels and that the effect is also modulated by differentiation of the cell to a neuronal phenotype.

Animals↗

PubMedDate not supplied

Serum cholesterol levels as a measure of frailty in elderly patients.

The authors evaluated the association between serum cholesterol levels and social, clinical, and functional characteristics in 637 elderly hospitalized patients (mean age = 79.1 years, range = 65-97) from the Geriatric Evaluation and Rehabilitation Unit (GERU) at P. Richiedei Hospital in Gussago, Brescia (Italy). Patients consecutively admitted to the GERU during an 18-month period underwent a multidimensional evaluation including information on demographics, cognitive status, physical health (number of chronic diseases and administered drugs), functional disability, and nutritional status. Mean cholesterol levels were significantly lower in men; persons living with others; older individuals; and individuals with cognitive impairment, poorer somatic health, higher disability, and a higher level of malnutrition. Lower serum cholesterol levels may be considered an independent hematologic marker of frailty in elderly hospitalized patients.

Aged↗

PubMedDate not supplied

Behavioral syndromes in Alzheimer's disease: description and correlates.

INTRODUCTION: Behavioral disturbances in patients with Alzheimer's disease (AD) are ill-defined conditions. We hypothesize that the many behavioral disturbances hitherto described and studied might be grouped into few syndromes with separate determinants and correlates. PATIENTS AND METHODS: 162 consecutive patients with probable AD admitted to a dementia unit were assessed by the UCLA Neuropsychiatric Inventory (NPI). RESULTS: Factor analysis was carried out on NPI subscales, leading to three syndromes: 'mood', 'psychotic' and 'frontal'. Patients with the 'psychotic' syndrome were older, had older age at dementia onset, had poorer cognition, were more often males, and had faster rate of dementia progression. Patients with the 'frontal' syndrome had higher education, longer disease duration, and slower rate of progression. DISCUSSION: Some combinations of behavioral disturbances occur more frequently together and might represent separate behavioral syndromes. Different clinical correlates of the syndromes suggest separate etiologies.

Aged↗

PubMedDate not supplied

Drug treatment in Lewy body dementia.

The treatment of Lewy body dementia (LBD) is particularly difficult for the co-occurrence of psychiatric and parkinsonian symptoms: antipsychotic drugs can worsen parkinsonism, and antiparkinsonian drugs can precipitate delusions and hallucinations. The aim of this study was to describe treatment strategies and outcomes of 10 clinically diagnosed LBD patients. Two patients had mainly motor symptoms, L-dopa therapy was moderately successful, and psychotic symptoms did not worsen. Eight had relevant psychiatric symptoms needing neuroleptic therapy. Six of these had sufficient response to low-dose neuroleptics and 2 did not respond; parkinsonism worsened in all 8 and L-dopa therapy or treatment with an antiparkinsonian drug was started in 6. L-Dopa or antiparkinsonian drugs were given also to those 2 patients who did not receive neuroleptics. Of the 8 patients taking L-dopa or antiparkinsonian drugs, 6 had a moderate or good response with no or only mild adverse effects. Psychiatric symptoms were sensitive to trazodone or clozapine in 2 patients, without side effects. A flow chart of drug therapy in LBD is proposed.

Aged↗

PubMedDate not supplied

Apolipoprotein E epsilon 4 allele in Alzheimer's disease and vascular dementia.

The frequency of the epsilon 4 allele of the apolipoprotein E (apoE) is increased in familial and sporadic late-onset Alzheimer's disease, but its prevalence in non-Alzheimer dementias in Caucasian populations is unknown. We found that the frequency of the apoE epsilon 4 allele was 0.45 in 93 Alzheimer's disease patients, 0.46 in 23 vascular dementia patients, 0.31 in 13 dementia of the frontal type patients, and 0.18 in 51 elderly controls. The association of apoE epsilon 4 allele is not unique to Alzheimer's disease, and its importance as a risk factor for the disease should be reconsidered.

Adult↗

PubMedDate not supplied

Usefulness of simple measures of temporal lobe atrophy in probable Alzheimer's disease.

Diagnosis of Alzheimer's disease is made on clinical grounds, and the availability of a simple and sensitive quantitative index of the disease might aid in the routine diagnosis. The aim of this study was to assess whether linear measures of brain atrophy as detected by magnetic resonance imaging can be helpful in the differentiation of mild to moderate Alzheimer's disease from nondemented elderly. Measures of global (bifrontal index and interuncal distance) and hippocampal (minimum thickness of the medial temporal lobe, hippocampal height, width of the choroid fissure, and width of the temporal horn) atrophy were taken from 26 cases and 21 controls. Measures of hippocampal atrophy were the most sensitive in the differentiation of cases from controls, and among them width of the temporal horn yielded the highest sensitivity, predicting the disease in 73% of cases with 95% specificity. A compound measure comprising width of the temporal horn, width of the choroid fissure, and hippocampal height increased sensitivity to 85%. These results suggest that selected simple indices of hippocampal atrophy might be useful in the diagnosis of Alzheimer's disease.

Aged↗

PubMedDate not supplied

The gain of apolipoprotein E genotyping to separate patients with Alzheimer's disease from normal individuals: relevance to community studies.

Neuropsychological screening tests such as the Mini Mental State Examination (MMSE) are commonly used for case finding in community studies on dementia or Alzheimer's disease (AD). However, the high proportion of false-positives is an important limitation to the feasibility of such studies. The aim of this study was to evaluate whether adding apoliporotein E (apoE) genotyping to the MMSE is followed by a significant reduction of the false-positive rate. Subjects were 70 AD patients (MMSE 13-28) and 70 normal controls (MMSE 25-30). Multivariable discriminant analysis was used to classify subjects on the basis of age, gender, MMSE score and the presence of the epsilon 4 allele of apoE. When sensitivity was set at 99%, the model including age, gender and MMSE had a false-positive rate of 13.5%, while adding epsilon 4 to the previous variables decreased this figure to 6.7%. In a hypothetical community study screening for AD in a population of 1,000,000, this would turn in a decrease of false-positives from about 19,000 to about 9,500. We conclude that the use of apoE genotyping in community case-finding studies is promising and should deserve further consideration.

Aged↗

PubMedDate not supplied

Predictors of mortality and institutionalization in Alzheimer disease patients 1 year after discharge from an Alzheimer dementia unit.

Several factors have been reported to predict death and institutionalization in demented patients, even if the results of the studies are often conflicting. We conducted a study on a group of 86 consecutive noninstitutionalized probable Alzheimer disease (AD) patients, to evaluate clinical and social factors predicting mortality and institutionalization 1 year after discharge from the Alzheimer Dementia Unit at 'Sacro Cuore Fatebenefratelli' Hospital, Brescia, Italy. The 1-year mortality rate was 13.9% and the 1-year rate of admission to a nursing home was 34%. Our data indicate that the number of lost functions on the Activity of Daily Living scale is the most important predictor of short-term mortality, independently of the degree of cognitive impairment, the duration of the dementia, the age of the patients and the number of chronic diseases. Our data also demonstrate that, in a short period of observation, behavioral disturbances (and in particular insomnia) and availability of social services play a major role in the decision to institutionalize AD patients.

Age Factors↗

PubMedDate not supplied

Neuropsychological heterogeneity in mild Alzheimer's disease.

In order to investigate neuropsychological differences in patients with mild AD, we carried out a pilot study on 28 patients with a clinical diagnosis of mild dementia (CDR: 0.5-1) using an extensive neuropsychological battery, in comparison with 28 normal controls. The results of a cluster analysis, applied on the neuropsychological variables, showed the existence of at least two main subgroups of patients. Cluster 1 patients had a mean age of 61.1 years and showed a greater impairment on measures of language, abstract reasoning and verbal fluency; cluster 2 patients, with a mean age of 72.0, had more severe impairment in memory function. These preliminary results may suggest the existence of different subtypes of AD characterized by selective neuropsychological deterioration in the early stages of the disease.

Aged↗