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Biomedical subjects

M Trabucchi

Publications and source records attributed to M Trabucchi.

At least 181 records · Page 10Linked to original sources

Dementia of the frontal type: neuropsychological and [99Tc]-HM-PAO SPET features.

Dementia of the frontal type (DFT) is a degenerative disorder with early behavioral and language disturbances and with relative preservation of memory and visuospatial abilities. On neuropathology, DFT lacks the pathologic hallmarks of Alzheimer's disease (AD). We assessed the neuropsychological and SPET imaging features of 11 DFT and 16 AD patients. The two groups had similar performances on verbal learning, while the former had significantly higher nonverbal learning scores. Testing of verbal and nonverbal instrumental abilities showed that this different behavior could be due to poorer verbal fluency of DFT patients, and not necessarily to poorer learning. Neuropsychological data indicated that the often reported sparing of memory in daily functions of DFT patients can also be shown with formal neuropsychological testing of nonverbal learning. SPET showed a comparatively higher perfusion deficit of frontal regions in the left hemisphere of DFT patients, suggesting that this region might be affected more often in the disease.

Aged↗

Reality orientation therapy in Alzheimer disease: useful or not? A controlled study.

The aim of this controlled study was to evaluate the effects of a long-term program of formal didactic group therapy [class reality orientation therapy (ROT)] in Alzheimer disease. The study was conducted in the day hospital of an Alzheimer Dementia Research and Care Unit (Brescia, Italy), a multidisciplinary care center providing diagnostic evaluation and treatment for elderly patients with cognitive impairment. The criteria for the inclusion of patients in the study were mild to moderate cognitive impairment [Mini Mental Status Examination (MMSE) between 11 and 24/30] and absence of major aphasia, blindness, and overt behavioral disturbances such as wandering or agitation. Sixteen patients constituted the experimental group and 12 the control group. The last cognitive, functional, and affective evaluation in the experimental and control group was performed 8.2 and 8.5 months after baseline assessment, respectively. The experimental group had repeated cycles of 1-month ROT classes, and 5-7 weeks was allowed between each cycle. Differential change for MMSE score between the two groups was significant. In the experimental group, there was mild improvement in MMSE score (0.68 point) at the last assessment, whereas the control group declined (-2.58 points). This treatment effect on MMSE score (3.27 points) was controlled for potential confounders in a multiple regression analysis. Adjusted treatment effect, including age, education, baseline MMSE, disease duration, disease severity, number of diseases other than Alzheimer, and time elapsing from baseline to last assessment, was very slightly lower: 3.12. In the experimental group, treatment effect was evaluated by comparing ROT cycle changes and resting period changes. A clearly significant treatment effect was found for MMSE and verbal fluency.

Aged↗

Protein kinase C activation and anti-amnesic effect of acetyl-L-carnitine: in vitro and in vivo studies.

Drugs belonging to different chemical classes having the ability to improve behavioral performance in animal learning and memory tests may share the common ability to stimulate protein kinase C activity in rat brain cortex. In vitro acetyl-L-carnitine (100 nM) promoted in rat brain cortex slices a significant increase in particulate activity associated with lower soluble protein kinase C activity and produced a direct stimulation of the enzyme in both the cortex and hippocampus. In vivo a significant increase in particulate protein kinase C activity was observed in the group of rats treated with 60 mg/kg acetyl-L-carnitine, a dose shown to be effective in improving the cognitive deficits induced by scopolamine in the Morris maze test. The results suggest that acetyl-L-carnitine increases particulate protein kinase C activity in the cortex both in vitro and in vivo. This effect in the in vivo experiments seems to be observed only with doses that are effective in improving the performance of rats in a spatial learning task.

Acetylcarnitine↗

Expression and regulation of calcium-independent protein kinase C in NG 108-15 cell differentiation.

Protein, mRNA and activity levels of the calcium-independent protein kinase C (nPKC) isoenzymes were examined in NG108-15 cells. Western blot analyses reveal that proliferating NG 108-15 cells express the delta, epsilon, and eta, but not the theta species. The atypical species PKC zeta was also detected. Differentiation of these cells with dibutyryl cAMP was associated with increase in the levels of PKC epsilon, with no significant changes in its steady-state mRNA levels. The levels of the other isoforms were not altered by the differentiated state. Similarly, no changes in nPKC activity were discerned in either the soluble or particulate fractions when histone or other proteins were used as substrates. These data suggest that the PKC epsilon isoform may be important for the production and maintenance of the differentiated state in NG 108-15 cells.

Animals↗

Modulatory mechanisms of cyclic AMP-stimulated steroid content in rat brain cortex.

The modulation of cyclic AMP dependent neurosteroidogenesis was studied in minces prepared from the cerebral cortex of adult rat. Forskolin or dibutyryl-cyclic AMP enhanced pregnenolone and progesterone production in a time and dose-dependent manner. The forskolin effect was mimicked by the cyclic AMP phosphodiesterase inhibitor isobutyl-methyl-xanthine, but not by the adenylate cyclase inactive forskolin analogue 1,9,dideoxy-forskolin. 4'-Chloro-diazepam, a high affinity ligand for the mitochondrial diazepam binding inhibitor (DBI) receptor, also elicited a time dependent increase in steroidogenesis. The forskolin and the 4'-chloro-diazepam stimulated pregnenolone increase was prevented by preexposing the rat brain cortical minces to 1-(2-chlorophenyl)-N-methyl-N-(1-methyl-propyl)-3-isoquinoline carboxamide (PK 11195), a high affinity ligand for the mitochondrial DBI receptor endowed with antagonistic properties. The protein synthesis inhibitor cycloheximide prevented the forskolin and 4'-chloro-diazepam stimulation of pregnenolone formation. In brain cortical minces of adrenalectomised/orchiectomised rats dibutyryl-cyclic AMP increased both pregnenolone and progesterone formation, while forskolin only increased progesterone. These data show that cyclic AMP enhances brain steroidogenesis by acting on a labile protein substrate which interacts with the mitochondrial DBI receptor.

1-Methyl-3-isobutylxanthine↗

Neurosteroids in the brain of handling-habituated and naive rats: effect of CO2 inhalation.

In rats habituated to the manipulation that precedes killing (handling-habituated) the cerebral cortical concentrations of pregnenolone and progesterone were significantly lower (-57% and -69%, respectively) than in naive animals. An acute stress, induced by CO2 inhalation, elicited a marked increase in the concentrations of pregnenolone, progesterone and deoxycorticosterone in the brain cortex and hippocampus of handling-habituated rats. An accepted stress, such as foot shock, also enhanced the brain cortical levels of pregnenolone, progesterone and deoxycorticosterone in handling-habituated rats. These data show that the rat brain cortical and hippocampal steroid content is related to the 'emotional state' of the animal.

Administration, Inhalation↗

Regulation of protein kinase C in NG108-15 cell differentiation.

The involvement of PKC in NG108-15 cell differentiation was investigated. Differentiation with dBcAMP was associated with a decrease in total cellular phorbol ester binding. The histone-directed PKC activity was decreased in the soluble fraction. Northern and Western blotting revealed the presence of only PKC alpha but not PKC beta and PKC gamma among the calcium-dependent isoforms. Differentiation induced a decrease of cytosolic PKC alpha immunoreactivity, with no changes of mRNA content or appearance of PKC beta and PKC gamma isoforms. The low levels of PKC alpha in the soluble fraction suggest that the mRNA for this species is less efficiently translated in differentiated NG108-15 cells. The data suggest that down-regulation of PKC alpha protein and kinase activity are associated with induction of neuronal morphology in NG108-15 cells.

Animals↗

Characterization and distribution of protein kinase C isoforms in human skin fibroblasts.

In the present study we have examined the distribution of several isoforms of protein kinase C, a lipid-regulated serine/threonine kinase essential for signal transduction and cell regulation, in cultured human skin fibroblasts. By Western blot analysis we have detected the presence of at least three of the known protein kinase C isoforms. The calcium-dependent protein kinase C alpha was primarily associated with the cytosolic fraction. Three non-calcium-dependent isoforms, protein kinases C epsilon, C delta, and C zeta, were also detected. Protein kinases C zeta and C delta were present primarily in the cytosol, while protein kinase C epsilon was associated primarily with the membrane fraction. Binding and activity studies were consistent with the pattern of expression and distribution defined by Western blot analysis. These results provide a useful frame of reference for the study of isoform-specific effects of protein kinase C in the regulation of cell growth and metabolism.

Adult↗

A nutritional index predicting mortality in the nursing home.

OBJECTIVE: To define a sensitive and specific index, based on nutritional indicators, predicting mortality in nursing home patients. DESIGN: A prospective cohort study. SETTING: A nursing home. MEASUREMENTS: Anthropometric and laboratory nutritional indicators were assessed in 104 nursing home elderly residents (20 males, 84 females). Patients were aged 60 years and older and had relatively good somatic health and nutritional status. Mortality data were collected over an 18-month follow-up period. Discriminant analysis was used to compute an adimensional measure (index) that could predict mortality with the highest sensitivity and specificity. RESULTS: Mortality was 0.20/year. A nonlinear, "U-shaped" relationship of cholesterol levels with mortality was found. A prognostic index based on cholesterol, lymphocyte count, mid-arm circumference, hemoglobin, age, and gender was obtained. Higher values of this index were associated with progressively higher risks at 12 months and 18 months. Sensitivity and specificity calculated on 18-month mortality were 80% and 78.4%, respectively. CONCLUSIONS: This index, based on simple measures, can be a useful tool in the evaluation of health status of the elderly living in nursing homes.

Aged↗

Single photon emission computed tomography with [99Tc]-HM-PAO and [123I]-IBZM in Alzheimer's disease and dementia of frontal type: preliminary results.

Dementia of frontal type (DFT) is a fairly common degenerative disease distinct from Alzheimer's disease (AD), whose reportedly distinctive instrumental feature is frontal lobe hypoperfusion on SPECT. We evaluated the cortical dopaminergic system in 6 AD, 5 DFT, and 6 control subjects with SPECT and both [99Tc]-HM-PAO, a perfusion tracer, and [123I]-IBZM, a D2 postsynaptic ligand. Both in AD and DFT patients, [99Tc]-HM-PAO SPECT showed a relative frontal hypoperfusion. On the contrary, [123I]-IBZM SPECT showed significantly reduced ligand uptake in superior frontal regions of DFT (0.89 +/- 0.08 relative to control subjects) as compared to AD patients (0.97 +/- 0.02; difference of means: 0.08, 95% Confidence Interval 0.004 to 0.156; p = 0.041). Results suggest more marked involvement of the frontal cortical dopaminergic system in DFT than in AD patients.

Aged↗

Fear of falling in nursing home patients.

The study analyzes the characteristics of 54 nursing home patients (12 male, 42 female; mean age 81.9 +/- 7.9 years) with and without the complaint of the fear of falling, and the association of this fear with falling and functional status. Patients who had a fear of falling at baseline (n = 25) had a lower functional status (Barthel Index) score (69.8 +/- 22.3 vs. 79.3 +/- 15.4), lower scores for balance (8.4 +/- 4.4 vs. 10.6 +/- 3.7) and gait (Tinetti; 6.7 +/- 3.3 vs. 8.3 +/- 2.6) and were taking a higher number of psychotropic drugs (0.8 +/- 1.1 vs. 0.2 +/- 0.5) than those with no fear (n = 29). At 24 months' follow-up, 25 subjects were still available for evaluation. Fear of falling at baseline was predictive of a decline in activities of daily living, as measured by the Barthel Index, in a multiple regression model, after controlling for baseline cognitive function and change in cognitive function, age, gender, balance and gait, frequency of psychotropic drug usage, and number of chronic symptoms. The findings of this study suggests that, in mobile patients, the fear of falling can be a clinically important predictor of functional decline.

Accidental Falls↗

Influence of nutritional intake on 6-year mortality in an Italian elderly population.

Many observations agree on the existence, in older ages, of nutritional deficiencies secondary to dietary intake. This study investigated to what extent dietary intake of calories, protein, iron and vitamins influences the 6-year mortality in an elderly population living at home. To prevent the confounding effect of non-dietary factors, such as gender, functional and health status, socio-economic conditions and health risk habits, these variable have also been considered. The dietary intake was calculated comparing the content of nutrients in self-reported, 24-hour diet, with the 1980 Recommended Dietary Allowances (RDA) obtaining a percentage for each nutrient. The percentage difference from the RDA was tested on 6-year mortality using a bivariate regression model. The intake of protein, vitamin A, thiamin, niacin, vitamin B6 and folate was significantly related to mortality: subjects with a lower dietary intake of those nutrients had a higher risk of death. When nutrient intake was tested in a multiple regression model, adjusted for non-dietary potential confounders, only folate was an independent predictor of mortality. This study shows that most of the dietary nutrient's intake is related to socio-economic and physical factors.

Age Factors↗

PKC translocation in rat brain cortex is promoted in vivo and in vitro by alpha-glycerylphosphorylcholine, a cognition-enhancing drug.

Protein kinase C (PKC) activity was measured in soluble and particulate fractions of rat individual brain areas after treatment with alpha-glycerylphosphorylcholine (GPC), a cognition-enhancing drug which promotes acetylcholine synthesis and release. The drug induced both in vivo and in vitro PKC translocation. In vivo, an increase of particulate PKC activity was observed 1 hour following the acute oral administration of a behaviorally active dose (600 mg/kg); the effect was transient. In vitro, GPC promoted PKC translocation in cortical slices at concentrations as low as 50 nM; the concentration-response curve was bell shaped. The increased PKC activity may be related to the cortical effects of GPC.

Amphetamine↗