PubMed Health⌕ Search

Biomedical subjects

A Ceci

Publications and source records attributed to A Ceci.

At least 19 recordsLinked to original sources
PubMed1995

BIMT 17, a 5-HT1A receptor agonist/5-HT2A receptor antagonist, directly activates postsynaptic 5-HT inhibitory responses in the rat cerebral cortex.

BIMT 17 (1-[2-[4-(3-trifluoromethyl phenyl) piperazin-1-yl] ethyl] benzimidazol- [1H]-2-one), a 5-HT1A receptor agonist/5-HT2A receptor antagonist (see Borsini et al., accompanying paper), in a dose range of 1-10 mg/kg i.v., dose-dependently inhibited the electrical activity of rat medial prefronto-cortical neurons, whereas buspirone, in a dose range of 0.1-1000 micrograms/kg, increased it. 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) and 1-[2-(2-thenoylamino)ethyl]-4-[1-(7-methoxynaphthyl)] piperazine (S 14671) presented biphasic patterns of response; they increased electrical activity at doses in the range of 0.1-10 micrograms/kg and 0.1-3 micrograms/kg i.v. respectively, and reduced it at high doses, 30-300 micrograms/kg and 10-30 micrograms/kg i.v., respectively. The inhibitory effect of BIMT 17 on the firing rate of neurons in the frontal cortex was antagonized by the 5-HT1A antagonists tertatolol and WAY 100135, and was still present after destruction of serotonin (5-HT) containing neuronal endings by the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT; 150 micrograms/rat, given intraventricularly), which reduced the cortical 5-HT content by 85%. This destruction of 5-HT neurons, while suppressing the ability of 8-OH-DPAT to inhibit the firing rate at high doses, did not change the excitatory action of this compound at low doses. The addition of ritanserin, a 5-HT2A receptor antagonist, potentiated both the excitatory and inhibitory effects of 8-OH-DPAT on neuronal electrical activity. Direct microiontophoretic application (100 nA/20 s) of 5-HT and BIMT 17, but not that of 8-OH-DPAT, onto medial prefronto-cortical neurons, decreased the firing rate of these neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1995

Effect of the 5-hydroxytryptamine3 receptor antagonist itasetron (DAU 6215) on (+)-N-allylnormetazocine-induced dopamine release in the nucleus accumbens and in the corpus striatum of the rat: an in vivo microdialysis study.

The in vivo brain microdialysis technique has been used to study the ability of itasetron, [DAU 6215, (3-alpha-tropanyl)1H-benzimidazolone-3-carboxamide hydrochloride], a novel 5-hydroxytryptamine3 (5-HT3)-receptor antagonist, to antagonize the effect of the sigma-agonist (+)-N-Allylnormetazocine (SKF 10,047) in inducing the release of dopamine from mesolimbic and nigrostriatal dopaminergic neurons, in comparison with haloperidol and clozapine. SKF 10,047 caused a dose-dependent increase in the release of endogenous dopamine preferentially from the nucleus accumbens septi with respect to the corpus striatum of the rat, the time to peak being 60 min from its administration. Itasetron (1-30 micrograms/kg s.c. given 45 min before SKF 10,047 5 mg/kg s.c.) dose dependently antagonized the SKF 10,047 response in the nucleus accumbens septi and not in the corpus striatum, without inducing by itself changes of basal DA output in either area at these doses. Another selective 5-HT3 receptor antagonist, ondansetron, at the dose of 10 micrograms/kg s.c., like itasetron, blocked the SKF 10,047-induced release of dopamine. At the dose of 100 micrograms/kg s.c., both itasetron and ondansetron failed to modify the effect of SKF 10,047 and increased DA release per se in the nucleus accumbens septi.

Animals↗
PubMed1994

Repeated treatment with fluoxetine decreases the number of spontaneously active cells per track in frontal cortex.

Repeated (10 mg/kg i.p. x 14 days, once daily), but not acute (10 and 40 mg/kg i.p., 30 min), treatment with fluoxetine decreased the number of active neurons in the frontal cortex 30 min (-55%) or 24 h (-62%) after the last drug injection. This result supports the view that repeated, but not acute, treatment with fluoxetine decreases the function of the frontal cortex.

Action Potentials↗
PubMed1994

The inhibitory effect of 8-OH-DPAT on the firing activity of dorsal raphe serotoninergic neurons in rats is attenuated by lesion of the frontal cortex.

The dose-response inhibitory effect of 8-OH-DPAT on the firing rate of dorsal raphe serotoninergic neurons was shifted 10-fold to the right after acute fronto-cortical deafferentation. This finding suggests that the inhibitory effect of 8-OH-DPAT on the dorsal raphe firing rate might be mediated indirectly by the frontal cortex.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1993

Effect of fluoxetine on the spontaneous electrical activity of fronto-cortical neurons.

The effect of fluoxetine on spontaneous extracellular activity of fronto-cortical neurons of chloral hydrate-anesthetized rats was investigated. Fluoxetine significantly increased the basal firing rate of cortical neurons in a dose-dependent manner (0.1-1000 micrograms kg-1 i.v.), with a maximum excitatory effect of 53% at 1000 micrograms kg-1. Selective destruction of ascending serotoninergic pathways induced by intracerebroventricular injections of 150 micrograms 5,7-dihydroxytryptamine, in desipramine-pretreated rats, antagonized the excitatory effect of fluoxetine. The present results suggest that fluoxetine significantly increases the electrical activity of the fronto-cortical neurons acting on serotoninergic uptake mechanisms localized at the level of raphe nuclei.

5,7-Dihydroxytryptamine↗
PubMed1993

Risk-directed therapy for childhood acute lymphoblastic leukemia. Results of the Associazione Italiana Ematologia Oncologia Pediatrica '82 studies.

BACKGROUND: In 1982, the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) started its third-generation study, aiming to improve previous results obtained by AIEOP '79 study and to deliver a standardized treatment to most Italian children with acute lymphoblastic leukemia (ALL). METHODS: We treated 902 children (older than 1 year and younger than 15 years of age) with newly diagnosed ALL in multicenter studies of risk-directed therapy (111 low risk [LR] from Study 8201; 570 average risk [AR] from Study 8202; and 117 and 104 high risk [HR] from Studies 8303 and 8503, respectively). Induction therapy was composed of vincristine, prednisone, and asparaginase for LR or AR patients and these agents plus daunorubicin, (Study 8503) or vincristine, prednisone, cytarabine, and intermediate-dose methotrexate (Study 8303) for HR patients. Central nervous system (CNS) preventive therapy consisted of intrathecal methotrexate only (LR), intrathecal methotrexate plus 18 Gy cranial irradiation (AR and HR Study 8503), or high-dose (HD) cytarabine (HR Study 8303). Reinduction therapy was vincristine/prednisone/daunorubicin for AR patients with cyclophosphamide added for HR patients in Study 8303 and HD asparaginase in Study 8503. LR patients did not receive intensification therapy. Continuation therapy comprised 6-mercaptopurine plus methotrexate and monthly pulses with vincristine plus prednisone for all patients, except for HR patients in Study 8303 who also received teniposide plus cytarabine. Weekly HD asparaginase was also given in Study 8503. Duration of treatment was 24 months for Studies 8201 and 8202, 15 months for Study 8303, and 22 months for Study 8503. The overall complete remission (CR) rate was 94.7% (97.3% for LR, 94.9% for AR, and 93.2% for HR). RESULTS: Overall 7-year event-free survival (EFS) was 53.6% (standard error [SE], 1.8). EFS was 60.8% in LR (SE, 4.7), 60.6% in AR at 7 years (SE, 4.7), and 18.5% in Study 8303 (HR) at 5 years (SE, 3.8). Because of the poor result in HR patients, a successor study (8503) was developed that yielded a 5-year EFS of 46.1% (SE, 5.1). Site-specific relapse rates were 18.5% (LR), 13.4% (AR), 35.1% (HR on 8303), and 18.3% (HR in Study 8503) for bone marrow and 9.2%, 7.9%, 17.5%, and 19.3%, respectively, for the CNS (isolated). Isolated testicular relapse was observed in 3.9% of male patients. CONCLUSIONS: This risk-directed therapy cured at least 50% of patients with ALL with relatively nonintensive therapy. The 80% overall survival rate for LR and AR patients at 7 years suggested that the total cure rate may be higher than 50% because of the significant salvage rate for patients who received antimetabolite-based therapy initially.

Adolescent↗
PubMed1993

Langerhans cell histiocytosis in childhood: results from the Italian Cooperative AIEOP-CNR-H.X '83 study.

Ninety patients with biopsy-proven Langerhans cell histiocytosis (LCH) were enrolled from June, 1983, to December, 1988, in the multicenter AIEOP-CNR-H.X. '83 study. They were divided into two groups: poor prognosis (PP), comprising 11 children with organ dysfunction (OD), and good prognosis (GP), made up of 79 patients without OD. Eighty-four patients were evaluable for treatment results. Among GP patients, 16 with a single lesion received only local treatment, while 59 entered a clinical trial of immunotherapy and/or monochemotherapy with vinblastine (VBL). Nonresponders, sequentially received doxorubicin (ADM) and then etoposide (VP16). PP patients were treated with 4 week cycles of vincristine, ADM, cyclophosphamide, and prednisone for nine courses. The overall survival was 92.8% (100% for GP patients and 45.5% for PP patients) at 48 months. The complete response (CR) rates for immunotherapy, VBL, ADM, and VP16 were 10%, 62.9%, 42.8%, and 88.2%, respectively. Two of the 11 PP patients had a CR (18.2%), while six died and three are still alive with recurrent disease. The overall incidence of disease-related disabilities was 47.7%, while that of diabetes insipidus was 20%. Monochemotherapy is probably adequate in GP patients, while more effective treatments are needed for PP patients.

Adolescent↗
PubMed1993

Mesulergine antagonism towards the fluoxetine anti-immobility effect in the forced swimming test in mice.

The anti-immobility effect of fluoxetine (40 mg kg-1) in the forced swimming test in mice was antagonized by the 5-HT1c/2 antagonist mesulergine (7.5 mg kg-1) and the dopamine D2 antagonist (+/-)-sulpiride (12.5 mg kg-1) but not by the 5-HT2/1C antagonist ritanserine (2 mg kg-1), the 5-HT1A/1B antagonist (-)-propranolol (20 mg kg-1) or the 5-HT3 antagonist DAU 6215 (0.1 mg kg-1). All compounds were administered intraperitoneally (i.p.) 6 min before fluoxetine, given i.p. 30 min before testing. The anti-immobility effect of fluoxetine was also prevented by pretreatment with p-chlorophenylalanine (300 mg kg-1 twice daily for 3 days) which produced an 80% reduction of 5-HT in brain. The results suggest that fluoxetine reduces immobility time in mice forced to swim, by acting indirectly through a mesulergine-sensitive site, probably the 5-HT1C receptor.

Animals↗
PubMed1992

Chronic treatment with DAU 6215, a new 5-HT3 receptor antagonist, causes a selective decrease in the number of spontaneously active dopaminergic neurons in the rat ventral tegmental area.

Electrophysiological techniques were used to study the effects of the new compound, DAU 6215 ((3-alpha-tropanyl) 1H-benzimidazolone-3-carboxamide chloride), a selective 5-HT3 receptor antagonist, on the activity of dopamine (DA)-containing neurons in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA). Acute i.v. injections of DAU 6215 did not cause any change in the basal firing rate of DA neurons in the SNc or in the VTA. Pretreatment with DAU 6215 did not modify the inhibitory effect of apomorphine on the firing rate of midbrain DA neurons. Acute s.c. administration of DAU 6215 caused a significant increase in the number of spontaneously active DA neurons in the VTA but not in the SNc. This effect was similar to that of acute clozapine, whereas acute haloperidol caused a significant increase of spontaneously active DA neurons in both the SNc and the VTA. Repeated consecutive s.c. administration of DAU 6215 and clozapine for 21 days produced a significant decrease in the number of spontaneously active DA neurons in the VTA but not in the SNc. Chronic haloperidol (21 days) decreased the number of DA cells both in the SNc and VTA. The effect of chronic DAU 6215 on the activity of VTA DA neurons was reversed by apomorphine, suggesting that these neurons were probably under a state of depolarization block. These findings indicate that DAU 6215 may have potential antipsychotic activity, probably associated with a low incidence of extrapyramidal side-effects.

Animals↗
PubMed1992

Effect of haloperidol and clozapine on (+)SKF 10,047-induced dopamine release: role of 5-HT3 receptors.

(+)SKF 10,047 preferentially increased dopamine release in the nucleus accumbens compared to the striatum. Dopamine output was evaluated in the same freely moving rats by trans-cerebral dialysis. Clozapine and DAU 6215, a 5HT3 antagonist, which itself did not modify dopamine release in both areas, selectively antagonized (+)SKF 10,047-induced dopamine release in the nucleus accumbens. Haloperidol by itself increased dopamine release in both areas and these effects were additive with those induced by (+)SKF 10,047.

Animals↗
PubMed1991

Allogeneic vs autologous BMT vs intensive chemotherapy in childhood AnLL during first complete remission: AIEOP experience. AIEOP Cooperative Group.

From 1982 to 1990, 340 children with newly diagnosed ANLL entered two consecutive AIEOP trials: LAM 8204 (1982-1987) and LAM 87 (1987-1990). Patients in both studies received identical remission induction with Daunorubicin and ARA-C. In the first study (LAM 8204) 167/171 patients were consolidated with four courses of DAT, followed by six additional courses of continuation therapy with three drug pairs given sequentially. Periodic intra-thecal ARA-C was used for CNS prophylaxis. For patients remaining on protocol, the OFS and EFS probability at 8 years was 35% and 30%, respectively. Induction response and EFS were adversely predicted by FAB MS subtype and hyperleukocytosis. In LAM 8204 trial there were 30 withdrawals represented by patients undergoing allogeneic (14) or autologous (16) BMT. For these patients the DFS probability at 5 years was 64% and 50%, respectively. On LAM-87 trial, 136/169 patients were evaluable and 98 (76%) attained CR. After consolidation with one course of DAT, patients with an HLA-identical donor underwent allogeneic BMT and those lacking a matched donor were randomized to receive either autologous BMT or the LAM 8204 postremission chemotherapy. The 2-year probability of DFS for allografted patients was 76% significantly higher (P = 0.0001) than that observed for patients on chemotherapy (12%) or autologous BMT (31%) arms.

Adolescent↗
PubMed1990

Non-competitive N-methyl-D-aspartate antagonists are potent activators of ventral tegmental A10 dopamine neurons.

The response of ventral tegmental (VTA) A10 dopamine neurons to a series of compounds covering the spectrum from high-affinity phencyclidine receptor ligands (MK-801, PCP) to high-affinity sigma-receptor ligands [+)-pentazocine, DTG) was measured using single-unit extracellular recording techniques in the rat. Dose-response comparisons revealed that MK-801 was 3, 6, 19 and 119 times more potent at activating A10 neurons than PCP, (+)-SKF-10,047, ketamine and (+)-pentazocine, respectively. DTG (1,3-di-o-tolylguanidine), the most selective sigma-ligand, and U50,488H, a kappa-opiate, failed to produce any stimulation of firing. Also, pretreatment with haloperidol, a potent sigma-receptor ligand, did not prevent MK-801-induced excitations. Thus, the activation of the A10-mesolimbic-mesocortical dopamine pathways by PCP, PCP-like drugs and sigma-psychotomimetics is mediated by the PCP receptor, not the haloperidol-sensitive sigma-receptor, with potencies directly correlated to their activity as non-competitive N-methyl-D-aspartate (NMDA) antagonists.

Animals↗
PubMed1989

Phencyclidine-induced activation of ventral tegmental A10 dopamine neurons is differentially affected by lesions of the nucleus accumbens and medial prefrontal cortex.

The nucleus accumbens and medial prefrontal cortex contain high concentrations of phencyclidine (PCP) binding sites as well as supply inhibitory and excitatory inputs to the ventral tegmental area (VTA). Thus these two regions could be instrumental in mediating the unique bimodal response of A10 neurons to systemically administered PCP. Therefore we evaluated electrophysiologically the effects of lesions of these two areas on this pattern of response. In sham-lesioned controls, i.v. injections of PCP elicited a typical dose-dependent bimodal effect which was characterized by an activation of A10 firing at low dose (reaching a maximum of +44% at 1 mg/kg) followed by a slowing of this response with larger doses. However, in animals with kainic acid or radiofrequency lesions of the nucleus accumbens, PCP produced only a unimodal response resulting in sustained and elevated (+88% in kainate and +55% in radiofrequency lesioned groups) firing rates. Notably, neither basal activity nor the degree of activation of the A10's at doses of PCP less than 1 mg/kg were affected by the lesions. In contrast, excitotoxic destruction of the medial prefrontal cortex had no effect on the response of A10 neurons to PCP even though basal activity was slightly elevated in this group. These results suggest that the inhibitory component of the bimodal response of VTA neurons to systemic PCP is mediated via feedback pathways from the nucleus accumbens, but that the mesocortical prefrontal cortex does not appear to modulate any portion of this bimodal response.

Animals↗
PubMed1989

Angioimmunoblastic lymphadenopathy with dysproteinemia: report of a case in infancy with review of literature.

A case of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) in infancy is reported. The disease had a mild onset with generalized lymphadenopathy, hepatosplenomegaly, thrombocytopenia, polyclonal hypergammaglobulinemia, and T-cell deficiency. The AILD course lasted more than 100 months, alternating clinical remission to recurrent relapses. Hepatitis B viral infection suddenly evolving to hepatic failure was the cause of death. From a rapid survey of the present knowledge, the nosology, immunological features, and therapy of AILD are discussed and a possible presumptive pathogenetic pathway is proposed.

Blood Protein Disorders↗