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G Pizzolato

Publications and source records attributed to G Pizzolato.

At least 73 records · Page 4Linked to original sources

Time-course and regional distribution of the metabolic effects of bromocriptine in the rat brain.

Local cerebral glucose utilization (LCGU) and motor behavior were examined in awake Fischer-344 rats after administration of the dopaminergic agonist bromocriptine (BROMO). LCGU was measured using the [14C]2-deoxyglucose technique in 63 brain regions at 1,2,3 or 4 h after BROMO 20 mg/kg, and at 4 h after BROMO 100 mg/kg i.p. At 2 h, LCGU was reduced significantly in 13% of the 63 regions examined. The affected regions are related to the topographical distribution of dopaminergic innervation in the brain. At 3-4 h, LCGU remained depressed in some of the above dopaminergic regions, but was elevated significantly in regions which are involved in sensorimotor function. BROMO also produced two behavioral effects depending on time after administration. Locomotor activity was depressed at 1-2 h, and stereotyped behavior appeared at 3-4 h. The time-dependent effects of BROMO may reflect progressively increasing brain concentrations of the drug or of its active metabolites. The coincidence of locomotor depression and reduction of LCGU in dopaminergic regions suggests a role of dopamine autoreceptors in regulation of motor function. Metabolic stimulation of many non-dopaminergic regions when stereotypy is evident suggests that circuit(s) involving these areas may contribute to stereotypy.

Animals↗

Reduced metabolic response of the rat brain to haloperidol after chronic treatment.

Local cerebral glucose utilization (LCGU) was determined, using the quantitative autoradiographic [14C]2-deoxy-D-glucose technique, in 47 brain regions of awake rats, after acute and chronic haloperidol (HAL) administration (1 mg/kg or 1 mg/kg/day). LCGU was reduced in fewer regions after chronic HAL (19%) than after acute HAL (72%); the average reduction for all regions was smaller (8% and 25%, respectively). The reduced metabolic effect of chronic HAL is not due to a lower brain concentration of the drug, since similar effects on LCGU were found in rats which received an acute i.p. injection of HAL (as in the acutely treated animals) after chronic administration of HAL for 3 weeks. Furthermore, continuous infusion of HAL for 3 weeks or 1 day resulted in similar tolerance to the metabolic effect of HAL. Tolerance was not observed in the mesocortical dopamine (DA) system. The present findings show that tolerance develops to the effect of HAL on cerebral metabolism, even after 1 day of HAL treatment. Lack of tolerance in the mesocortical pathway may implicate this system in the neuroleptic effect of chronic HAL.

Animals↗

Reduced metabolic response of the aged rat brain to haloperidol.

Local cerebral glucose utilization (LCGU) was determined in 49 brain regions of 3-, 12-, 24-, and 33-month-old awake Fischer-344 rats, at 30 to 120 min after administration of the dopaminergic antagonist haloperidol (HAL) at 1 mg/kg (i.p.). The quantitative autoradiographic [14C]-2-deoxyglucose technique was employed. In 3-month rats, HAL produced statistically significant (p less than 0.05) reductions in LCGU in 63% of the brain regions examined, including those having dopaminergic as well as non-dopaminergic function. With increasing age, LCGU was progressively less affected by HAL. Significant declines in LCGU occurred in 21 to 23% of the observed regions in 12- and 24-month rats, and in 10% of the 49 regions in 33-month-old rats. The peak effects of HAL on LCGU occurred later in the 33-month- than in the 3-month-old rats (90 and 60 min after HAL, respectively). The behavioral effect (catalepsy) of HAL was less in old than in young rats. Age-related differences in the cerebral metabolic and behavioral responsivities of rats to HAL are not due to differences in brain concentrations of HAL, as higher concentrations are obtained in older animals (Kapetanovic, I.M., D.J. Sweeney, and S.I. Rapoport (1982) J. Pharmacol. Exp. Ther. 221: 434-438). The differences correlate with known age-dependent structural and biochemical deficits of the central dopaminergic system and indicate reduced functioning of that system in the rat brain after 12 months of age.

Aging↗

Haloperidol and cerebral metabolism in the conscious rat: relation to pharmacokinetics.

The time course and distribution of alterations in cerebral metabolic activity after haloperidol administration were evaluated in relation to the pharmacokinetics of haloperidol and the topography of the dopaminergic system in the brain. Local cerebral glucose utilization was measured, using the 2-deoxyglucose technique, in awake rats after i.p. administration of the dopamine antagonist haloperidol (0.5 or 1 mg/kg). Haloperidol significantly reduced glucose utilization in 60% of 59 brain regions examined, but produced a large increase in the lateral habenula. The regional distribution of changes in glucose utilization was not closely related to the known anatomy of the brain dopaminergic system. The time course of the effect of haloperidol on cerebral metabolism was different for the two doses studied (0.5 and 1 mg/kg), and was not simply related to estimated brain concentrations of haloperidol. However, a linear relation between the metabolic effect and the time-integrated brain concentration was demonstrated. These results show that haloperidol has an effect on CNS metabolic activity that is more widespread than would be predicted from the topography of the dopaminergic system; this may be due to indirect propagation of the primary effects of haloperidol. The metabolic response to haloperidol depends on brain concentration and duration of exposure to the drug.

Animals↗

Biochemistry and histology of the connective tissue of Dupuytren's disease lesions.

When compared to age-matched control aponeurosis, lesions of Dupuytren's disease contain higher contents of water, collagen and chondroitin-sulphate, as well as increased proportions of soluble collagens and of reducible cross-links; these indicate synthesis of new collagen. The lesions show also increased amounts of type III collagen and an increased hydroxylation and glycosylation of the reducible cross-links. All these parameters are characteristic of granulation and scar tissues. Type III collagen was located by means of immunofluorescence on thin argyrophilic fibres and also within the large fibre bundles which appeared to be disrupted into microbundles. The increase of type III collagen and the presence of myofibroblasts in the apparently unaffected aponeurosis show that the disease is widespread and suggest that it is initiated within the aponeurosis and propagated by the cells migrating along the collagen bundles.

Adult↗

Comparative studies in two cases of testicular feminization syndrome, one with and the other without the fluorescent distal band q12 of the Y.

In two patients with testicular feminization syndrome, one Yq12-positive and the other Yq12-negative, we compared phenotype, gonadal histology and ultrastructure, in vivo steroid response of the testes to the administration of exogenous gonadotropin during adrenal suppression, and of the adrenal gland to ACTH. The assumption that the constitutive Y heterochromatin could function as a regulator of steroid biosynthesis and metabolism, with or without effect at other levels, was not firmly supported by the observations reported here. However, further studies along this line may help elucidate the biologic role of this portion of the Y chromosome in humans.

Adrenal Glands↗

Malignant transformation of a spinal cord ganglioglioma--case report and review of the literature.

Gangliogliomas are tumors of mixed glial and neuronal phenotype that usually have a benign clinical course. Rare cases display anaplastic features at the time of first presentation or progress to anaplastic gliomas over extended times. We report on a ganglioglioma of the spinal cord that recurred as a malignant glioma one and a half years after resection. The initial neoplasm was composed of a mixture of well-differentiated ganglionic and astrocytic cells. The recurrent tumor was an anaplastic small-cell glioma. The sole unusual aspect in the initial neoplasm was an abundance of small vessels with calcified walls, which mimicked a vascular malformation.

Adult↗