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Biomedical subjects

M Trabucchi

Publications and source records attributed to M Trabucchi.

At least 19 recordsLinked to original sources

Cyclic AMP-dependent increase of steroidogenesis in brain cortical minces.

Rat brain cortical minces were incubated with forskolin and dibutyryl-cyclic AMP for 60 and 30 min, respectively. The concentrations of pregnenolone, progesterone and desoxycorticosterone in this preparation were significantly increased by both substances. The results indicate that, in brain tissue, steroidogenesis appears to be regulated by receptor transduction mechanisms that operate through adenylate cyclase.

Animals

Assessment of quality of life in the elderly assisted at home through a Tele-Check service.

This study evaluates the effects of a Tele-check/Tele-emergency service on the quality of life in the elderly. Through telephone interviews a questionnaire has been repeatedly administered to explore various psychological, somatic, and social aspects in a random sample of 574 subjects aged 65 years and over (mean = 76.8 years). The findings suggest that the elderly helped by the service (in its 'control' functioning) make less demands on health facilities (GPs visits, number of days in hospital) as compared to controls. Implications are presented and discussed.

Aged

Protein kinase C increase in rat brain cortical membranes may be promoted by cognition enhancing drugs.

Protein Kinase C (PKC) activity was measured in soluble and particulate fractions of rat individual brain cortices after in vivo treatment with two cognition enhancers: oxiracetam and alpha-glicerylphosphorylcholine. Both drugs induced an increase (+40-50%) of PKC particulate activity at 1 hr after the treatment. The effect was transient; at 5 hours PKC activity was lower than in controls. The dose response curve to oxiracetam was bell shaped, the increase of PKC being significant at 100 mg/kg. At higher doses the drug induced a decrease in enzyme activity. The increased PKC activity may be related to the cortical effects of these compounds.

Animals

G protein modulation of omega-conotoxin binding sites in neuroblastoma x glioma NG 108-15 hybrid cells.

Electrophysiological evidence shows that voltage-dependent calcium channel (VDCC) activity can be regulated by a large number of neurotransmitters. In particular, guanine nucleotide binding regulatory protein (G protein)-mediated inhibitory modulation of the channel activity has been deduced from evidence that GTP analogues and purified G proteins are able to mimic this effect. The G proteins involved are pertussis toxin (PTx) sensitive. The purpose of the present study was to investigate, using biochemical techniques, whether G protein activation modulates the recognition site for omega-conotoxin GVIA (CgTx), a peptide neurotoxin that selectively labels a population of high-threshold VDCC. Undifferentiated and differentiated (1 mM dibutyryl cyclic AMP, 4 days) NG 108-15 cells were used. In both crude cellular extracts specific binding of 125I-CgTx was characterized. Differentiation induced a sixfold increase in the number of binding sites and doubled the KD value. The in vitro addition of guanylylimidodiphosphate (GMP-PNP; a nonhydrolyzable analogue of GTP) to extracts prepared from differentiated cells reduced the 125I-CgTx binding by 48%. This effect, observed in undifferentiated cells as well, was also caused by other triphosphate guanine nucleotides, such as GTP, but not by guanosine 5'-O-(2-thiodiphosphate) or adenine nucleotides. Treatment of the cells with PTx prevented the GMP-PNP effect. Moreover, the results obtained after preincubation with specific antisera raised against the alpha subunits of Gi1-2 and Go suggest that Go is the G protein responsible for the observed effect.

Animals

SPECT and dementia.

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Alzheimer Disease

Evidence for protein kinase C modulation of the ciliary muscle response to carbachol and desensitization.

The role of protein kinase C (PKC) in the desensitization of muscarinic receptor-mediated responses in bovine ciliary muscle was examined. Exposure of the bovine ciliary muscle to phorbol esters, used to activate PKC, resulted in antagonism of muscarinic receptor-mediated contraction. On the other hand, staurosporine, a known PKC inhibitor, caused a significant potentiation of the contractile effect induced by carbachol. Staurosporine reduced the desensitization induced by repeated additions of carbachol and completely suppressed that induced by phorbol esters. The results also indicate that desensitization mediated by phorbol esters as well as that mediated by muscarinic receptor agonists is heterologous.

Alkaloids

The aging brain: protein phosphorylation as a target of changes in neuronal function.

There is evidence that senescence affects neurotransmission at different levels. In particular, this review summarizes the studies on age-dependent modifications in protein phosphorylation, which represents the final pathway in the action of transmitters and hormones at neuronal level. Cyclic AMP-dependent protein kinase and protein kinase C have been reported to be modified during aging in various cerebral areas; the changes may involve either enzyme activity or substrate availability. These findings can be related to the alterations in neurotransmitter function and synaptic efficiency observed in the senescent brain. The activity of the other types of protein kinases (tyrosine-, cGMP-, calcium/calmodulin-dependent) during aging needs to be explored. An emerging point is the role of protein phosphorylation in the transfer of membrane signals to the nucleus, for the activation or disactivation of specific genes responsible for long-term neuronal events. Along this view, alterations in protein kinase pathway during senescence would ultimately affect gene expression, resulting in long term modifications of cell function. The reviewed literature opens the perspective of restoring some of the deficits associated with senescence by modulating protein phosphorylation pathway.

Aging

Effect of a new cognition enhancer, alpha-glycerylphosphorylcholine, on scopolamine-induced amnesia and brain acetylcholine.

The present study investigates the effect of the administration of alpha-glycerylphosphorylcholine (alpha-GPC) on scopolamine-induced amnesia and on brain acetylcholine (ACh) levels and release in rats. The results indicate that alpha-GPC, when administered orally, reverses the amnesia caused by scopolamine in passive avoidance. The peak effect is observed using 600 mg/kg IG, 5 h before training. The effect of the drug is long lasting (up 30 h) in accordance with its pharmacokinetic characteristics. Since, alpha-GPC administered IG is cleaved within the gut mucosal cells to glycerophosphate and free choline, it is tempting to speculate that this drug acts by increasing the ACh precursor pool. This view is supported also by the observation that alpha-GPC partially counteracts the decrease of brain ACh levels elicited by scopolamine administration. The effect is observed in the hippocampus and cortex, but not in the striatum. Moreover, in ex vivo experiments, alpha-GPC is able to increase the amount of ACh released by rat hippocampus slices following potassium stimulation.

Acetylcholine

Evaluation of beta-endorphin/beta-lipotropin immunoreactivity content in the CSF of patients affected by deafferentation pain syndromes.

Beta-endorphin/beta-lipotropin immunoreactivity (BE/BLPH-IR) content was evaluated in the CSF of patients suffering by deafferentation pain syndromes. BE/BLPH-IR CSF concentrations of these patients were compared with those obtained in a group of patients affected by low back pain and in a control group without pain problems. No statistically significant variation in BE/BLPH-IR levels were found between controls and subjects with different types of chronic pain.

Adult

The value of memory.

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Activities of Daily Living

Calcium antagonists inhibit met-enkephalin immunoreactive material release: in vitro and ex vivo experiments.

Depolarizing stimuli increase the release of neurotransmitter met-enkephalin from rat striatal slices. Bay K8644, a calcium agonist, significantly enhances the submaximal release of this peptide. Several organic calcium antagonists, including nimodipine, nifedipine, nicardipine, gallopamil and flunarizine, are able to inhibit the potassium-evoked met-enkephalin release both in vitro and ex vivo. The data suggest that the release of this neuropeptide is modulated by calcium antagonist-sensitive calcium channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy

Characterization of peripheral benzodiazepine receptors in human blood mononuclear cells.

In the present study, peripheral-type benzodiazepine receptors in human circulating mononuclear cells were characterized, using [3H]PK 11195 as specific ligand. The specific binding was saturable, with a Bmax of 14 pmol/mg protein and a Kd of 7 nM. The pharmacological characterization, using different displacing drugs, indicated a mitochondrial type of peripheral benzodiazepine receptor since it was not coupled to the GABA receptor and was displaced by protoporphyrin IX. These data indicate that human circulating mononuclear cells possess benzodiazepine recognition sites, similar to non-neuronal receptors. The role of these receptors and possible modifications in different diseases need to be investigated.

Adult

Nutritional intake, socioeconomic conditions, and health status in a large elderly population.

The nutritional intake of a large population of noninstitutionalized older people living in an urban area was studied in relation to socioeconomic conditions (living environment, income, and education) and health status (affective, functional, and physical health) to identify the subgroups at risk for malnutrition. Twenty-four-hour dietary recall was used to determine the percentage of older subjects with dietary intake of specific nutrients below two thirds of the 1980 Recommended Dietary Allowances. Ninety percent of the older people examined showed inadequate intake of thiamine and vitamin B6, and 30% to 40% demonstrated deficiencies of vitamin A, vitamin C, niacin, vitamin B12, calcium, and iron; only 10% of subjects had inadequate intake of protein. Poor nutritional intake was correlated more strongly with socioeconomic conditions, functional level, and affective status than with physical health status.

Activities of Daily Living

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.

Anxiety Disorders

Modulation of dihydropyridine-sensitive calcium channels: a role for G proteins.

The present study investigates the effect of G protein activation on dihydropyridine recognition sites in PC12 cell membranes. The addition of a stable analogue of GTP, GMP-PNP, increases the displacement of tritiated PN 200-110 produced by Bay K 8644 without modifying the one produced by nitrendipine. This effect is prevented by Pertussis toxin treatment. Functional studies based on the measurement of intracellular calcium concentrations by means of the fura 2 technique show that Pertussis toxin reduces the ability of Bay K8644 to potentiate the increase of cytosolic calcium elicited by 80 mM K+. The results support the hypothesis that a G protein may modulate the activity of voltage-dependent, dihydropyridine-sensitive calcium channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy

Decrease in phorbol ester receptors in human brain tumors.

We have characterized the specific binding of [3H]-phorbol-12,13-dibutyrate in the white and gray matter of normal human brain and in cerebral tumors as an index of the availability of protein kinase C enzyme molecules. White matter has less than 50% phorbol-ester-binding capacity in comparison to gray matter. The binding is lower in tumors of glial origin when compared with normal white matter. Tumors of nonglial origin such as neurinoma and meningioma have a lower binding capacity than glial tumors. Metastatic tissues have the lowest binding capacity. The analysis of binding parameters in tumors and in the corresponding normal peritumoral tissues confirms the decreased binding capacity of neoplastic tissues in comparison to tissues not undergoing malignant transformation. These data suggest that brain glial tumors have a low availability of protein kinase C enzyme molecules and point to the potential involvement of this system in malignant transformation of human brain cells.

Adult

Direct coupling of a G-protein to dihydropyridine binding sites.

Electrophysiological data support the existence of GTP-binding proteins interacting with voltage dependent calcium channels. Along this line the present study investigates the effect of GMP-PNP, a stable GTP analogue, on the displacement of [3H]-PN 200-110 binding by agonist and antagonist dihydropyridines in synaptic membranes prepared from rat cortex. The results show that GMP-PNP increases the ability of the agonist dihydropyridine BAY K 8644 to displace [3H]-PN 200-110 binding. The in vivo treatment with Pertussis Toxin abolishes the effect produced by the non-hydrolysable GTP analogue.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy