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C Marchetti

Publications and source records attributed to C Marchetti.

At least 37 records · Page 2Linked to original sources
PubMed2001

Lead inhibition of NMDA channels in native and recombinant receptors.

NMDA channels are key targets for lead (Pb2+) neurotoxicity and Pb2+-induced inhibition of NMDA current is age- and subunit-dependent. In rat cerebellar granule cells maintained in high KCl, glycine affinity as well as sensitivity to ifenprodil change significantly with the days in vitro, indicating a reduction of NR2B subunit expression. Pb2+ blocked NMDA current with IC50 approximately 4 microM and this effect decreased significantly during the second week in vitro. In Xenopus laevis oocytes expressing recombinant NR1-NR2A, NR1-NR2B or NR1-NR2C receptors, Pb2+ inhibited glutamate-activated currents with IC50 of 3.3, 2.5 and 4.7 microM respectively. These data indicate that Pb2+ action is dependent on subunit composition and suggest that down-regulation of the NR2B subunit is correlated to a diminished sensitivity to Pb2+ inhibition.

Animals↗
PubMed2001

Modulation of T-cell activation by the glucocorticoid-induced leucine zipper factor via inhibition of nuclear factor kappaB.

Previously a novel gene was identified that encodes a glucocorticoid-induced leucine zipper (GILZ) whose expression is up-regulated by dexamethasone. This study analyzed the role of GILZ in the control of T-cell activation and its possible interaction with nuclear factor kappaB (NF-kappaB). Results indicate that GILZ inhibits both T-cell receptor (TCR)-induced interleukin-2/interleukin-2 receptor expression and NF-kappaB activity. In particular, GILZ inhibits NF-kappaB nuclear translocation and DNA binding due to a direct protein-to-protein interaction of GILZ with the NF-kappaB subunits. Moreover, GILZ-mediated modulation of TCR-induced responses is part of a circuit because TCR triggering down-regulates GILZ expression. These results identify a new molecular mechanism involved in the dexamethasone-induced regulation of NF-kappaB activity and T-cell activation. (Blood. 2001;98:743-753)

Active Transport, Cell Nucleus↗
PubMed2001

Evidence for increased extracellular K(+) as an important mechanism for dorsal root induced alternating rhythmic activity in the neonatal rat spinal cord in vitro.

Intracellular recording from rat lumbar motoneurones showed that patterned electrical stimulation of one dorsal root induced alternating patterns typical of fictive locomotion, accompanied by a reduction in the antidromic spike afterhyperpolarization (AHP). Since the AHP depended linearly on extracellular K(+) ([K(+)](o)), from the AHP fall we calculated that [K(+)](o) rose to 7.9+/-0.4 mM, a value within the 7-10 mM range known to elicit fictive locomotion. To confirm the specificity of this approach we also tested concentrations of N-methyl-D-aspartate (2 microM) below threshold for fictive locomotion, and we observed that, despite strong excitation, the estimated [K(+)](o) was 6 mM, i.e. outside the range for fictive locomotion. We suggest that synaptic activity induced by a certain pattern of electrical stimulation of afferent fibres evoked persistent elevation in [K(+)](o) which triggered the locomotor network to generate rhythmic patterns.

Animals↗
PubMed2001

Alternating rhythmic activity induced by dorsal root stimulation in the neonatal rat spinal cord in vitro.

Electrical stimuli applied to a single dorsal root (DR) of the neonatal rat spinal cord in vitro were used to test the possibility that the central pattern generator responsible for locomotion could be activated by synaptic inputs. Brief pulse trains evoked oscillatory patterns recorded from pairs of lumbar ventral roots. These patterns alternated rhythmically between the left and right sides and between predominantly flexor and extensor motoneuronal pools on the same side, thus displaying properties similar to the fictive locomotor pattern elicited by bath-applied excitatory transmitter agonists like NMDA and serotonin. Usually pulse trains rather than single pulses were necessary to induce these patterns, the period of which was independent of stimulation frequency (1-10 Hz) and only moderately dependent on stimulus intensity. Patterns reached a steady rhythm during the stimulus train, lasted for 50 +/- 20 s with gradual period lengthening and finally ceased. Since DR stimuli activated the central pattern generator for locomotion in the rat isolated spinal cord, it is suggested that sensory inputs from the periphery can reach the spinal locomotor network and trigger its operation.

Animals↗
PubMed2001

Multiple pathways of Pb(2+) permeation in rat cerebellar granule neurones.

The pathways of lead (Pb(2+)) uptake were studied in fura-2-loaded cerebellar granule cells from 8-day-old rats. In a nominal Ca-free external bath, Pb(2+) (5-50 microM) determined an increase of the fluorescence emission ratio (R = E(340)/E(380)) even in the absence of any specific stimulus. This rise was dose-dependent, was not significantly affected by mM Mg(2+) or Ca(2+), but it was readily reversed by the membrane-permeant heavy metal chelator tetrakis(2-pyridylmethyl) ethylene-diamine (TPEN, 100 microM), indicating that it was due to Pb(2+) influx. The rate of rise, dR/dt, was increased up to a factor of 5 by depolarizing high-KCl solution, indicating a sizeable permeation through voltage-dependent channels. This effect was neither antagonized by nimodipine, nor enhanced by BayK8644, but it was slackened by omega-agatoxin IVA (200 nM), suggesting an involvement of non-L-type calcium channels. Pb(2+) influx was also stimulated by glutamic acid or NMDA in the presence of 10-30 microM glycine, but only in Mg-free solution, suggesting that glutamate channels of the NMDA type are an additional pathway of Pb(2+) uptake. Pb(2+) caused a time-, dose- and stimulus-dependent saturation of the dye, whose intracellular concentration is approximately 10 microM, indicating that intracellular Pb(2+) can readily reach a concentration in the micromolar range. These results indicate that the particular vulnerability of neurones to Pb(2+) poisoning is linked to the presence of specific transport systems, which mediate the rapid uptake of Pb(2+) into the neurone.

Animals↗
PubMed2001

Treatment of carcinoma of the parotid gland: the results of a multicenter study.

PURPOSE: This study analyzed the prognostic factors for carcinoma of the parotid gland and the role of surgery alone or with radiotherapy in treating these lesions. METHODS: Forty-five patients with malignant parotid tumors were studied retrospectively. Patients were treated by combined surgery and radiation therapy between 1984 and 1995 at the Maxillo-Facial Departments of the General Hospitals of Bologna and Parma. Resection was conservative when possible, depending on the extent of the tumor. The median follow-up time was 54 months. Data regarding incidence, tumor stage and grade, local control, distant metastases (calculated with the Kaplan-Meier method), and survival were analyzed. Cox's multiple linear regression was used to identify patient and tumor characteristics with the greatest prognostic significance. RESULTS: The actuarial 5- and 8-year disease-free survival rates were 81% and 62%, respectively. Multivariate analysis showed that tumor stage was a more prognostic variable than tumor grade. Residual microscopic disease at the excision margins was also an important prognostic variable. Laterocervical metastases affected 4 patients (9%), and distant metastases appeared in 8 patients (18%). CONCLUSIONS: Postoperative irradiation is indicated for patients with stage III and IV disease, patients with positive excision margins, and for patients with lymph node metastases.

Actuarial Analysis↗
PubMed2001

Levetiracetam does not modulate neuronal voltage-gated Na+ and T-type Ca2+ currents.

This study investigated whether the mechanism of action of levetiracetam (LEV) is related to effects on neuronal voltage-gated Na+ or T-type Ca2+currents. Rat neocortical neurones in culture were subjected to the whole-cell mode of voltage clamping under experimental conditions designed to study voltage-gated Na+ current. Additionally, visually identified pyramidal neurones in the CA1 area of rat hippocampal slices were subjected to the whole-cell mode of voltage clamping under experimental conditions designed to study low-voltage-gated (T-type) Ca2+ current. LEV (10 microM-1 mM) did not modify the Na+ current amplitude and did not change (200 microM) the steady-state activation and inactivation, the time to peak, the fast kinetics of the inactivation and the recovery from the steady-state inactivation of the Na+ current. Likewise, LEV (32-100 microM) did not modify the amplitude and did not change the steady-state activation and inactivation, the time to peak, the fast kinetics of the inactivation and the recovery from the steady-state inactivation of the T-type Ca2+current. In conclusion, neuronal voltage-gated Na+ channels do not appear directly involved in the antiepileptic mechanism of action of LEV, and LEV was devoid of effect on the low-voltage-gated (T-type) Ca2+ current in hippocampal neurones.

Animals↗
PubMed2001

Neuronal bursting induced by NK3 receptor activation in the neonatal rat spinal cord in vitro.

Intracellular recording from lumbar motoneurons and extracellular recording from ventral roots of the neonatal rat isolated spinal cord were used to study the mechanisms responsible for the excitation mediated by NK3 tachykinin receptors. The selective NK3 agonists senktide or [MePhe7]neurokinin B induced a slow depolarization with superimposed oscillations (mean period +/- SD was 2.8 +/- 0.8 s) that, in the majority of cases, showed left-right alternation at segmental level and were synchronous between L2 and L5 of the same side. During agonist wash out (5-20 min) a delayed form of hyperexcitability emerged consisting of bursts lasting 8 +/- 2 s (average interburst interval 55 +/- 21 s) with superimposed oscillations usually with homosegmental alternation and heterosegmental synchronicity. Such bursting was accompanied by depression of GABAergic dorsal root potentials evoked by dorsal root stimulation and of the recurrent inhibitory postsynaptic potential recorded from motoneurons. Despite bursting, motoneuron membrane potential returned to baseline while input resistance was increased. Bursts were a network-dependent phenomenon triggered by previous NK3 receptor activation because bursting was suppressed by glutamate receptor antagonists and was insensitive to motoneuron membrane potential or subsequent application of an NK3 receptor antagonist. NK3 receptors operated synergistically with N-methyl-D-aspartate (NMDA) and 5-hydroxytryptamine (5-HT) to trigger fully alternating locomotor-like rhythms while NK3 receptor antagonism disrupted the same rhythm. In summary, in the neonatal rat spinal cord NK3 receptors could trigger rhythmic activity predominantly with alternation at segmental level but with synchronous coupling between ipsilateral motor pools. NK3 receptor activation could also facilitate fictive locomotor patterns induced by NMDA and 5-HT.

Animals↗
PubMed2000

Effect of P2 purinoceptor antagonists on kainate-induced currents in rat cultured neurons.

The action of purinergic antagonists on kainate-induced currents was studied in rat cortical neurons in primary culture using the whole-cell configuration of the patch-clamp technique. The amplitude of the currents induced by kainate in cortical neurons was concentration-dependent (EC(50)=106 microM). Pyridoxal-phosphate-6-azophenyll-2',4'-disulphonic acid 4-sodium (PPADS), a P2X antagonist, was ineffective in the reduction of the kainate-induced current in cortical neurons, while 2, 2'-pyridylisatogen (PIT), basilen blue (BB) and suramin, respectively two selective P2Y and a non-selective P2 receptor antagonist, caused a reduction in the amplitude of the current induced by kainate. BB decreased the inward current induced by kainate at all holding potentials and the reduction was dose-dependent (EC(50)=34 microM). The total conductance of the neurons for the kainate-induced current was significantly reduced (P<0.01) and the effect was completely reversible. BB furthermore reduced the kainate-induced current in granule and hippocampal neurons and decreased the amplitude of the alpha-amino-3-hydroxy-5-methyl-4-isoxalepropionic acid (AMPA)-evoked current in cortical neurons. Cholera toxin (ChTx) did not affect the action of BB on the kainate-induced currents in cortical neurons and moreover, when guanosine 5'-o-(3-thiotriphosphate) (GTPgammaS) was added to the electrode solution, the kainate-induced currents were still reduced by 100 microM BB. The maximal response to kainate decreased in the presence of 20 microM BB without changing its EC(50), indicating a non-competitive mechanism of inhibition. These results demonstrate that preferential P2Y receptor antagonists are able to modulate the kainate and AMPA-induced currents in central neurons, suggesting a potential use of these compounds as neuroprotective agents.

Action Potentials↗
PubMed2000

Individual differences in the use of social information in foraging by captive great tits.

We investigated individual differences in copying behaviour of captive great tits, Parus major, by analysing their response to a tutor indicating a new feeding site. We used two groups, each of seven male birds, labelled 'fast' and 'slow' explorers based on previous studies in which consistent individual differences in the speed of exploring were found. The birds were trained to search for food hidden in a number of differently coloured and shaped feeders, and later to search in only one type of feeder. During the tests, food was absent and the birds were observed in two different situations: alone or in the presence of a tutor, a bird that had been trained to feed in a different kind of feeder. When alone, slow birds readily extended their search to other feeders while fast birds did not change their routine of visiting the previously rewarded ones. In the presence of the tutor, the opposite occurred: slow birds did not change their behaviour while fast birds significantly increased their visits to the feeders indicated by the tutor. Fast and slow individuals thus differ in their foraging and copying behaviour, consistent with the producer-scrounger model. Copyright 2000 The Association for the Study of Animal Behaviour.

Journal Article↗
PubMed2000

Cognition in action: testing a model of limb apraxia.

Assessment of limb apraxia is still suffering from Liepmann's legacy and performance in gesture-processing tests is generally rendered by classifying patients' profile according to the classic clinical labels of ideomotor and ideational apraxia. At odds with other cognitive functions, interpretation of apraxia has suffered from a lack of a reliable model which does justice to its complexity. Recently such a model has been proposed (Rothi et al., 1991, 1997). In this article a modified version of this model is presented and predictions are made according to its functional architecture. Five different patterns of impairment of gesture processing are postulated. To validate the predicted performance profiles, 19 left-hemisphere-damaged patients were assessed by means of an ad hoc battery of four praxis tests. Four of the five predicted apraxia patterns were observed, the fifth being more equivocal. These results support the need to overcome the simplistic dichotomous view of apraxia and confirm the fruitfulness of a model of normal gesture processing in order to understand dissociations in apraxia.

Aged↗
PubMed2000

Dexamethasone increases the incorporation of [3H]serine into phosphatidylserine and the activity of serine base exchange enzyme in mouse thymocytes: a possible relation between serine base exchange enzyme and apoptosis.

The exposure of phosphatidylserine toward the external surface of the membrane is a well-established event of programmed cell death. The possibility that an apoptotic stimulus influences the metabolism of this phospholipid could be relevant not only in relation to the previously mentioned event but also in relation to the capability of membrane phosphatidylserine to influence PKC activity. The present investigation demonstrates that treatment of mouse thymocytes with the apoptotic stimulus dexamethasone, enhances the incorporation of [3H]serine into phosphatidylserine. Cell treatment with dexamethasone also enhanced the activity of serine base exchange enzyme, assayed in thymocyte lysate. Both the effects were observed at periods of treatment preceding DNA fragmentation. The addition of unlabelled ethanolamine, together with [3H]serine to the medium containing dexamethasone-treated thymocytes lowered the radioactivity into phosphatidylserine. Serine base exchange enzyme activity was influenced by the procedure used to prepare thymocyte lysate and was lowered by the addition of fluoroaluminate, that is widely used as a G-protein activator. The increase of serine base exchange enzyme activity induced by dexamethasone treatment was observed independently by the procedure used to prepare cell lysate and by the presence or absence of fluoroaluminate.

Aluminum Compounds↗
PubMed2000

Hemimandibular hyperplasia: treatment strategies.

Hemimandibular hyperplasia is a well-defined, rare asymmetrical mandibular malformation. It is characterized by diffuse enlargement of the condyle, the condylar neck, and the ramus and body of the mandible. Because the anomaly begins before puberty, it is understandable that the maxilla follows the downward growth of the mandible. Pathogenesis is due most likely to clear hyperactivity in the condyle, which can be documented histologically with an actively proliferating cartilage. Therapy is largely based on the patient's age. The authors present their series of nine individuals with hemimandibular hyperplasia treated with various surgical methods between 1992 and 1994. A therapeutic approach called orthopedic maxillary management applied to two of the nine patients is presented. The objective is to maintain the occlusal maxillary plane in a correct position in growing patients. All clinical results, except one, were satisfying and showed good postoperative stability.

Adolescent↗
PubMed2000

Modification of transepithelial ion transport in human cultured bronchial epithelial cells by interferon-gamma.

Human bronchial epithelial cells were treated in vitro with interferon-gamma or tumor necrosis factor-alpha to assess their effect on transepithelial ion transport. Short-circuit current measurements revealed that Na(+) absorption was markedly inhibited by interferon-gamma (10-1,000 U/ml). The cystic fibrosis transmembrane conductance regulator was also downregulated by interferon-gamma as evident at the protein level and by the decrease in the cAMP-dependent current. On the other hand, interferon-gamma caused an increase of the current elicited by apical UTP application, which is due to the activity of Ca(2+)-dependent Cl(-) channels. Tumor necrosis factor-alpha caused few changes in ion transport. Transepithelial fluid transport was measured in normal and cystic fibrosis cells. At rest, both types of cells showed an amiloride-sensitive fluid absorption that was inhibited by interferon-gamma but not by tumor necrosis factor-alpha. Our results show that interferon-gamma alters the transepithelial ion transport of cultured bronchial cells. This effect may change the ion composition and/or volume of periciliary fluid.

Biological Transport↗
PubMed2000

Effect of interleukin-2 on generation of natural killer cells: role of major histocompatibility complex class I in B6 and TAP-1-/- mice.

Long-term bone marrow cultures were used to investigate the effect of IL-2, a cytokine widely used in immunotherapy, on natural killer cell differentiation. Specifically, the role of MHC was evaluated by comparing normal B6 and class I-deficient TAP-1-/- mice. The number of cells generated after a 13-day culture was the same in cell cultures from TAP-1-/- or B6 mice but the relative number of natural killer cells, identified as NK-1.1+CD3- cells by flow cytometry analysis, was increased in TAP-1-/- compared to B6 cultures (74.4% and 63.9%, respectively). Addition of an anti-class I mAb determined a strong inhibition of natural killer cell generation in B6 cultures, and its effect was specific since no effect was seen in TAP-1-/- cell cultures. TAP-1-/- natural killer cells or the few natural killer cells escaping the inhibitory effect of anti-class I mAb, were less cytotoxic than total B6 natural killer cells against target cell lines of different haplotype.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Relationship of myoma cell size and menopausal status in small uterine leiomyomas.

CONTEXT: Although myomas shrink after menopause, the cellular mechanism for this phenomenon has received little attention. It was recently demonstrated that fibrous degeneration is significantly associated with postmenopausal status in both small and large myomas. OBJECTIVE: The purpose of the present study was to evaluate whether reduction in myoma cell size is also associated with postmenopausal status in small myomas. DESIGN: Tumor size and patient age have also been related to fibrous degeneration in small (<1 cm) myomas. Therefore, in the present study, 10 pairs of premenopausal and postmenopausal small myomas were matched within 3 years for patient age, within 1 mm for size, and within 1 grade for degree of fibrous degeneration. Most of the women were in their 50s, the decade during which postmenopausal fibrous degeneration in small myomas is most prevalent. Myoma cell size was derived by morphometric evaluation of relative myoma cell area (correcting for percentage of stroma, as measured by point counting) and by direct counting of the number of myoma cells per unit area in trichrome-stained sections. RESULTS: Small myomas from postmenopausal women had significantly (P <.05) smaller cell sizes than did size-matched myomas from age-matched premenopausal women. Myoma cell sizes and nucleus-cell (N/C) ratios were highly variable, especially in premenopausal myomas. CONCLUSIONS: Reduction in myoma cell size is significantly associated with postmenopausal status in small uterine leiomyomas and may be an important mechanism for postmenopausal shrinkage of myomas. In addition, the high variability of myoma cell size and N/C ratio may further support the somatic mutation theory (ie, the theory that diverse mutations may account not only for variations in the growth potential of uterine myomas, but also for variations in their cellular details).

Cell Size↗