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M Morelli

Publications and source records attributed to M Morelli.

At least 73 records · Page 4Linked to original sources
PubMed1994

Behavioural sensitization in 6-hydroxydopamine lesioned rats involves the dopamine signal transduction: changes in DARPP-32 phosphorylation.

"Priming" is a phenomenon of behavioural sensitization observed in unilaterally 6-hydroxydopamine lesioned rats following exposure to a dopamine agonist. After priming, a single dose of the D1 agonist SKF 38393 (3 mg/kg) produces contralateral turning, while the same dose is inactive in drug-naive, lesioned animals. The molecular mechanisms of "priming" were investigated here by studying the phosphorylation of dopamine and adenosine 3'-5' monophosphate regulated phosphoprotein (DARPP-32), a dopamine- and cyclic AMP-regulated phosphoprotein functionally linked to D1 receptors in striatum. Dephospho-form of DARPP-32 were measured by a back-phosphorylation assay. All assays were performed in striata from both lesioned and unlesioned sides. A significant decrease of dephospho-DARPP-32 (27%) was observed in the denervated striatum of primed rats, indicating an increased phosphorylation in vivo of DARPP-32 in response to the D1 agonist. The levels of DARPP-32 protein, as measured by quantitative immunoblotting, remained unchanged in all experimental groups. This study shows that priming is expressed as an increased transduction of the D1 receptor message.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1994

[Aarskog syndrome. A case report].

A case of Aarskog syndrome in a 10-year-old boy born to an epileptic woman is reported. Clinical features and genetics of the condition are reviewed. An underestimated incidence of the syndrome related to its mild phenotypical appearance is suggested. Finally the association between Aarskog syndrome and maternal epilepsy is discussed.

Abnormalities, Multiple↗
PubMed1993

L-dopa stimulates c-fos expression in dopamine denervated striatum by combined activation of D-1 and D-2 receptors.

Administration of L-dopa to unilaterally 6-hydroxydopamine-lesioned rats, activates the early gene c-fos in the lesioned caudate-putamen. D-1 receptor blockade by SCH 23390, prevented L-dopa-induced Fos-like immunoreactivity in the whole caudate-putamen, while D-2 receptor blockade by raclopride reduced Fos-like immunoreactivity only in the dorso-lateral portion. The results suggest that L-dopa induces c-fos primarily through an activation of D-1 receptors, while D-2 receptor stimulation plays a facilitatory influence on D-1-mediated c-fos expression.

Animals↗
PubMed1993

Local cerebral glucose utilization after D1 receptor stimulation in 6-OHDA lesioned rats: effect of sensitization (priming) with a dopaminergic agonist.

In rats bearing unilateral 6-hydroxydopamine (6-OHDA) lesions of the dopaminergic nigro-striatal neurons, a single administration of a D-2 agonist (LY 17155) potentiates the contralateral turning induced by a D-1 agonist (SKF 38393). To identify the neural substrate of this form of sensitization (priming), we studied the local cerebral glucose utilization (lCMRglc) in 6-OHDA lesioned animals treated, 3 days apart, as follows: (1) saline-saline, (2) LY 171555-saline, (3) saline-SKF 38393 and (4) LY 171555-SKF 38393. The unilateral 6-OHDA lesion per se (Sal-Sal) produced increases in lCMRglc in the globus pallidus (GP) and in the lateral habenula (LH) of the lesioned hemisphere. lCMRglc in LY-Sal group were similar to those measured in the Sal-Sal group. Administration of SKF 38393 to drug-naïve rats (Sal-SKF) abolished the lesion-induced metabolic asymmetry in the LH but did not have any effect on the GP; furthermore, it increased lCMRglc in the substantia nigra pars reticulata (SNr) of the lesioned side. After priming with LY 171555, administration of SKF 38393 (LY-SKF) produced marked metabolic asymmetries by increasing lCMRglc in the SNr and entopeduncular nucleus (EP), and decreasing it in the LH of the lesioned side. These changes were also significant when compared to the corresponding values of the other experimental groups. Again, in LY-SKF group no modification of the lesion-induced metabolic asymmetry in the GP was found.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

Expression of c-fos protein in the experimental epilepsy induced by pilocarpine.

The expression of the c-fos proto-oncogene, as estimated by immunohistochemistry of the FOS nuclear protein, was studied in both focal and generalized seizures induced in rats by systemic administration of pilocarpine. Focal seizures, as indicated by the occurrence of stereotyped oral movements, chewing and sniffing, were evoked by either a subconvulsant dose of pilocarpine (200 mg/kg) or the association of a convulsant dose of pilocarpine (400 mg/kg) with SCH 23390, a selective D-1 dopamine receptor antagonist. This seizure pattern resulted in FOS accumulation in certain limbic areas, namely, the piriform cortex, amygdala, and olfactory tubercle. On the other hand, in rats developing generalized seizures, accumulation of FOS was also found in hippocampus, cingulate cortex, frontal cortex, striatum, accumbens, as well as in certain thalamic nuclei. Generalized seizures, including motor limbic seizures and status epilepticus, were induced by either a convulsant dose of pilocarpine (400 mg/kg) or a low dose of pilocarpine (15-200 mg/kg) combined with either lithium or the D-1 selective agonist SKF 38393. These findings indicate a close correlation between the sequence of behavioural alterations induced by pilocarpine and the proto-oncogene activation. The results provide the basis for mapping the areas of origin and the pathways of generalization of seizure activity. As shown by the effects of dopamine receptor agonists and antagonists, the process of generalization appears to be controlled by the dopamine system.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

Stimulation of dopamine transmission in the dorsal caudate nucleus by pargyline as demonstrated by dopamine and acetylcholine microdialysis and Fos immunohistochemistry.

The effect of pargyline on dopamine neurotransmission was investigated by trans-striatal microdialysis combined with Fos immunohistochemistry. Pargyline, 75 mg/kg i.p., increased dopamine and acetylcholine output while drastically decreased dopamine deaminated metabolites. Administration of pargyline resulted in the appearance of Fos-positive nuclei distributed along a gradient around the dialysis probe. Pretreatment with the D1 antagonist SCH 23390 potentiated the effect of pargyline on dopamine output while preventing that on acetylcholine output and on Fos formation. Similarly, lack of calcium in the perfusion medium abolished the effect of pargyline on dopamine and acetylcholine output and on Fos formation. In rats not implanted with dialysis probes pargyline administration resulted in only rare Fos-positive nuclei in the dorsal caudate. The present study indicates that pargyline stimulates dopamine transmission in the dorsal caudate in the area around the dialysis probe but not distant from the fibre or in unimplanted rats. This effect appears to reflect an interaction between the drug-induced changes and those locally elicited by the probe.

Acetylcholine↗
PubMed1993

Blockade of muscarinic receptors potentiates D1 dependent turning behavior and c-fos expression in 6-hydroxydopamine-lesioned rats but does not influence D2 mediated responses.

In rats with a unilateral 6-hydroxydopamine lesion of the dopaminergic nigrostriatal pathway, blockade of muscarinic receptors by scopolamine potentiates the contralateral turning induced by selective dopaminergic D1 agonists (SKF 38393, A 68930), but does not influence the contralateral turning induced by the D2 agonist LY 171555. Studies on the expression of the early gene c-fos as reflected by the immunohistochemical demonstration of the Fos protein, show that administration of scopolamine (5 mg/kg, i.p.) potentiates c-fos expression elicited by SKF 38393 (1.5 mg/kg, s.c.) in the caudate-putamen of the lesioned side. The results indicate that cholinergic transmission is differentially involved in the behavioral expression of D1 versus D2 receptor stimulation in a denervated condition and suggest that blockade of central cholinergic transmission might be useful in improving the antiparkinsonian efficacy of D1 receptor agonists.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

Metabolic mapping of the pharmacological and toxicological effects of dopaminergic drugs in experimental animals.

Functional consequences of pharmacological and toxicological manipulations of the dopaminergic systems were evaluated by means of the 2-[14C]deoxyglucose (DG) method for measuring local rates of cerebral glucose utilization. Administration of dopamine agonist drugs modifies glucose metabolism in selected brain areas. Several factors, such as the compound used, the dose, length, and modality of the treatment, and the interval of time between the end of the treatment and the measurement of glucose utilization, contribute to define the topography and intensity of the changes. The differences refer to distinct activation of subtypes of dopamine receptors, to secondary involvement of other neurotransmitter receptor systems, and to modification of the receptor sensitivity occurring during the treatment. Other variables that interfere with the motivated behavior induced by psychostimulants may also affect the metabolic pattern. A few changes in glucose utilization are, however, common to most dopamine agonist drugs. High doses, which induce stereotypic behavior, produce metabolic changes in the extrapyramidal system. Low doses of psychostimulants, which elicit locomotion and exploratory behavior and produce reinforcement, increase glucose metabolism in the limbic system, particularly in the nucleus accumbens. Metabolic mapping in monkeys bearing 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced lesions of the dopaminergic areas in the brainstem contributed to define the key role of the striatopallidal pathway in the production and maintenance of the motor abnormalities that characterize parkinsonism. Metabolic patterns associated with unilateral 6-hydroxydopamine lesion of the nigrostriatal neurons in the rat are modified by dopamine agonist drugs. Specific changes are produced by selective D1 or D2 agonists. In rats bearing unilateral 6-hydroxydopamine lesion, the DG method also revealed functional effects produced by the interaction between D1 and N-methyl-D-aspartate receptors.

Animals↗
PubMed1993

Creatine-kinase isoenzyme pattern in colonic infarction consequent to acute aortic dissection. A case report.

Bowel infarction can complicate acute aortic dissection (AAD); in that case early diagnosis, which decreases the high mortality, is often difficult. We report the case of one patient who underwent surgery for AAD and developed a colonic infarction, which was clinically manifest on the 4th postoperative day. However, bowel ischemia was suspected already 48 hours after surgery, on the basis of the suggestive CK pattern and the absence of myoglobin in plasma. Total CK activity reached the highest level only 48 hours after surgery (92,800 U/l); the peak was coincident with LDH, which increased proportionally less; CK-MM constituted 100% of total CK activity. The absence of myoglobin in plasma excluded the presence of rhabdomyolysis. We conclude that such laboratory findings suggest the occurrence of severe bowel ischemia.

Acute Disease↗
PubMed1993

[Liver injury in abdominal trauma. Review of the literature and personal observations].

In patients who suffered abdominal trauma, the liver is the most frequently involved organ, except the spleen. The % rises from 1520% to 30% if trauma is closed or open. Liver injury may spread from a simple parenchymal contusion to a break in vessels or biliary ducts. Life risk is related to hemorrhage. The mortality is due to: 1) extension of the injured liver surface, 2) possible damage to big vessels, 3) intra or extra abdominal associated injury in case of multiple trauma. It is important to known the kind of injury to choose the best therapy, not necessary surgical. The authors report on 15 patients with thoracoabdominal trauma and liver damage, comparing their cases with literature observations.

Abdominal Injuries↗
PubMed1992

Metabolic mapping of the synergism between MK-801 and SKF 38393 in rats with unilateral lesions of the dopaminergic nigrostriatal pathway.

In rats with a unilateral lesion of the dopaminergic nigrostriatal pathway with 6-hydroxydopamine, blockade of N-methyl-D-aspartate receptors by MK-801 strongly potentiated the turning behavior induced by D-1 receptor stimulation. To determine the functional consequences of such positive interaction we measured the local rates of cerebral glucose utilization (lCMRglc) in lesioned rats treated with MK-801 (0.1 mg/kg) and the D-1 agonist SKF 38393 (1.5 mg/kg), either alone or in combination. Treatment with each drug separately did not induce any substantial change in lCMRglc besides an increase in the metabolic activity of the dorsomedial caudate and entopeduncular nucleus (EP) of the lesioned side of MK-801 treated rats, as compared to the same side of lesioned rats treated with vehicle. Combined administration of MK-801 + SKF 38393 increased lCMRglc in the EP (+77%) and in the substantia nigra pars reticulata (SNr) (+30%) of the lesioned side as compared with the intact side, while it decreased lCMRglc in the lateral habenula (-26%). These changes were also significant when compared to the lesioned side of vehicle treated rats. The results suggest that while the caudate putamen might be the primary site of MK-801 and SKF 38393 positive interaction, the EP and SNr are the striatal efferent areas where this positive interaction is expressed.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1992

Localization of MPP+ binding sites in the brain of various mammalian species.

The distribution and density of 3H-MPP+ binding sites were studied by in vitro quantitative autoradiography in the brain of the mouse, rat and monkey. The highest levels of 3H-MPP+ specific binding were observed in rat brain. The substantia nigra in rat and monkey, and the anterior caudate-putamen formation in mouse and monkey showed the lowest density of autoradiographic grains. The presence of a relatively high density of MPP+ sites in the hippocampus of all species studied could be of interest to explain some effects of MPTP administration on convulsions caused by chemoconvulsants. The finding of a 60-70% reduction of 3H-MPP+ binding sites in the rat caudate-putamen, on the side of quinolinic acid infusion and no changes after 6-hydroxydopamine lesion of dopaminergic nigrostriatal neurons suggests the presence of these sites mainly on striatal cells. The results suggest that the distribution of MPP+ binding sites in brain would not seem to be related to MPTP toxicity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1992

Blockade of N-methyl-D-aspartate receptors potentiates dopaminergic responses in the 6-OHDA model of Parkinson: differential role of D-1 and D-2 receptors.

The non competitive antagonist of N-methyl-D-aspartate (NMDA) receptors MK-801, at doses which did not produce any behavioural modification per se, increased by about 40% the contralateral turning induced by the dopaminergic (DA) D-1/D-2 agonist L-dopa in rats bearing a unilateral lesion of the DA nigro striatal neurons. Administration of MK-801 in combination with selective agonists of the D-1 (SKF 38393) or D-2 (LY 171555) receptor, induced an increase of about 280% of D-1 mediated turning and a 70% decrease of D-2 mediated turning. Analysis of the potentiation of L-dopa mediated turning by MK-801 after selective D-1 receptor blockade by SCH 23390, revealed that the increase of turning was related to the stimulation of D-1 receptors by L-dopa. Immunocytochemical visualization of the proto-oncogene c-fos in the caudate-putamen (CPu) of lesioned rats, revealed a sparse c-fos positive nuclei in the lesioned CPu of rats treated with SKF 38393 alone, while after combined administration of MK-801 and SKF 38393 dense labelling of nuclei was found. The results indicate that blockade of NMDA receptors by MK-801 acts synergistically with D-1 agonists in the induction of turning after DA denervation and shows that these changes are correlated with c-fos induction in specific areas of the CPu.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1992

Combined microdialysis and Fos immunohistochemistry for the estimation of dopamine neurotransmission in the rat caudate-putamen.

Extracellular dopamine (DA) concentrations estimated by transcerebral dialysis and D1-dependent c-fos expression, as demonstrated by Fos immunohistochemistry, were studied after blockade of DA reuptake by GBR-12909. Rats implanted with dialysis probes in the dorsal caudate-putamen did not show any Fos-positive neuronal labeling in the implanted area or in the rest of the caudate-putamen. Administration of GBR-12909 dose-dependently increased DA output in dialysates and resulted in the appearance in the caudate-putamen of Fos-positive neurons whose density was related to the dose of GBR-12909 and to the increase in extracellular concentrations of DA. The D1 antagonist SCH-23390 blocked GBR-12909-induced activation of Fos while potentiating the stimulation of DA output. The results show that following blockade of DA reuptake by GBR-12909, the induction of Fos is related to stimulation of D1 receptors by extracellular DA. Combination of brain dialysis with Fos immunohistochemistry might provide a method for estimating the functional significance of extracellular DA as measured by brain microdialysis.

Animals↗
PubMed1992

[Respiratory inductive plethysmography in the functional evaluation of patients undergoing coronary by-pass surgery].

The functional respiratory changes following coronary by-pass surgery were previously evaluated with the traditional spirometric method. Aim of this work is to introduce the respiratory inductive plethismography (RIP), a well known non-invasive technique, into the study of those volumetric and ventilatory modifications. Eight cardioischemic patients were selected: all but one were free from pulmonary disorders. The tidal volume, the respiratory rate, the minute ventilation, the vital capacity and the relation between the abdominal and the thoracic part of the ventilatory act, were measured in the pre-intervention session and in the 1st, 3rd and 7th day after the operation of coronary by-pass. In the same sessions, except the 1st day after surgery, the maximal respiratory pressures were evaluated with traditional manometers. The functional changes of the examined parameters, statistically studied with the variance analysis, closely resemble the spirometric modifications registered by other authors. Furthermore the relative contributions of the thoracic and abdominal compartments of the pulmonary ventilation were evaluated, thanks to the non-invasive plethysmographic method. Rip makes it possible to measure the ventilatory pattern and some pulmonary volumes in the very early phases after thoracic surgery, without any trouble for the patient and in a non-collaborative state of consciousness, too.

Aged↗