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C Taddei

Publications and source records attributed to C Taddei.

At least 37 records · Page 2Linked to original sources
PubMed1996

Single-center analysis of 468 first cadaveric kidney allografts with a uniform ATG-CsA sequential therapy.

Progress in clinical management and sophistication of immunological treatment of kidney allografts depend upon continuous reassessment of the risk factors related to pre- and post-graft information according to the therapeutical strategies used. We studied predictive factors of long-term graft survival (up to 9 years) and of kidney graft function at one year after surgery in a single-center population of 468 first cadaveric kidney recipients treated with a uniform immunosuppression induction regimen of anti-thymocyte globulin, followed by cyclosporine A. The statistical analysis showed that long-term graft survival was highly correlated with the occurrence of one or more acute cellular rejections and with the timing of these episodes. In addition, this uniformly treated series of patients confirmed the potential importance of gender matching. The magnitude of anti-HLA immunization and delayed graft function were also strongly linked to low graft survival rates. We found no significant influence of HLA matching, with serological HLA typing, on graft loss. The quality of graft function at one year was found to be a strong prognostic factor of long-term graft survival. In addition, the impact of pre- and post-graft parameters were studied in terms of prediction of one-year graft function. A stepwise multivariate analysis showed that graft function at one year was a multivariate phenomenon strongly correlated with a history of acute rejection episodes and with donor and recipient age. However, these 3 factors could account for only 15% of the graft function deterioration, the remaining 85% might be explained in part by chronic cyclosporine toxicity and/or chronic rejection.

Adolescent↗
PubMed1995

Receptor binding profile of cyclazosin, a new alpha 1B-adrenoceptor antagonist.

The binding profile of cyclazosin, a new prazosin-related alpha 1-adrenoceptor antagonist, at alpha 1-, alpha 2-adrenoceptors, dopamine D2 and 5-HT1A receptors was compared to that of 5-methylurapidil, spiperone, risperidone and other prazosin-related ligands. In addition, cyclazosin was investigated at native and cloned alpha 1-adrenoceptor subtypes. Cyclazosin showed high specificity for alpha 1-adrenoceptors and a 10-15-fold selectivity for alpha 1B (alpha 1b)-adrenoceptors with respect to the alpha 1A (alpha 1a) subtype (pKi values of 9.23-9.57 and 8.18-8.41, respectively). However, it failed to discriminate between cloned alpha 1b and alpha 1d-adrenoceptors (pKi values of 9.23 and 9.28, respectively).

Adrenergic alpha-Antagonists↗
PubMed1995

The alpha 1d-adrenoceptor subtype is involved in the noradrenaline-induced contractions of rat aorta.

The pA2 value of several alpha 1-adrenoceptor antagonists on noradrenaline-induced contractions of rat aorta, and their affinity for the cloned alpha 1a-, alpha 1b- and alpha 1d-adrenoceptor subtypes were evaluated. Selective or moderately selective alpha 1d-, partially selective alpha 1b-, selective alpha 1a- and non subtype-selective alpha 1-adrenoceptors antagonists were included in the study. The potency of these compounds on rat aorta was well correlated with the affinity observed for the alpha 1d-adrenoceptor subtype. A poor correlation was found for the alpha 1b- and alpha 1a-subtypes. These results suggest that the alpha 1d-subtype plays a determining role in rat aorta contractions induced by noradrenaline.

Adrenergic alpha-Antagonists↗
PubMed1995

Mediation of noradrenaline-induced contractions of rat aorta by the alpha 1B-adrenoceptor subtype.

1. The subtypes of alpha 1-adrenoceptor mediating contractions to exogenous noradrenaline (NA) in rat aorta have been examined in both biochemical and functional studies. 2. Incubation of rat aortic membranes with the irreversible alpha 1B-adrenoceptor antagonist, chloroethylclonidine (CEC: 10 microM) did not change the KD of [3H]-prazosin binding in comparison to untreated membranes, but reduced by 88% the total number of binding sites (Bmax). 3. Contractions of rat aortic strips to NA after CEC (50 microM for 30 min) incubation followed by repetitive washing, showed a marked shift in the potency of NA and a partial reduction in the maximum response. The residual contractions to NA after CEC incubation were not affected by prazosin (10 nM). 4. The competitive antagonists prazosin, terazosin, (R)-YM-12617, phentolamine, 5-methylurapidil and spiperone inhibited contractions to NA with estimated pA2 values of 9.85, 8.54, 9.34, 7.71, 7.64 and 8.41, respectively. 5. The affinity of the same antagonists for the alpha 1A- and alpha 1B- adrenoceptors was evaluated by utilizing membranes from rat hippocampus pretreated with CEC, and rat liver, respectively. 5-Methylurapidil and phentolamine were confirmed as selective for the alpha 1A-adrenoceptors, whereas spiperone was alpha 1B-selective. 6. A significant correlation was found between the pA2 values of the alpha 1-adrenoceptor antagonists tested and their affinity for the alpha 1B-adrenoceptor subtype, but not for the alpha 1A-subtype. 7. In conclusion, these findings indicate that in rat aorta most of the contraction is mediated by alpha 1B-adrenoceptors, and that the potency (pA2) of an antagonist in this tissue should be related to its antagonistic effect on this subtype of the alpha 1-adrenoceptor population.

Adrenergic alpha-Antagonists↗
PubMed1994

Solubilization and characterization of d-fenfluramine binding sites from bovine cerebral cortex.

Stable d-Fenfluramine binding activity was obtained in high yields, in cholate extracts of bovine cerebral cortex crude membrane preparations. Dissociation constant (Kd 17 nM), stereoselectivity and the rank order of potencies of various serotonin uptake inhibitors were similar to those measured in native membranes. The inhibitory effect of Na+ ions was also maintained in the soluble state, since the presence of 100 mM Na+ leads to an even greater reduction of the binding than in membrane-associated binding sites. Photoaffinity labeling of soluble binding sites with p-[125I]d-Fenfluramine has led to the identification of a single specific band of molecular weight around 40-50 kDa. This suggests that d-Fenfluramine binding sites are separate molecular entities from the serotonin transporter, that belongs to a family of integral membrane proteins of 68-73 kDa molecular weight.

Affinity Labels↗
PubMed1993

Characterization of alpha 1-adrenoceptor subtypes in prostate and prostatic urethra of rat, rabbit, dog and man.

The alpha 1-adrenoceptor subtypes present in the smooth muscle of urethra and prostate of different animal species, including man, were characterized by using receptor binding techniques. In prostatic urethra and prostate membranes, [3H]prazosin labelled a single population of alpha 1-adrenoceptors (Hill coefficient not different from unity) with a high affinity in the range 0.21-0.51 nM. The number of specific [3H]prazosin binding sites was partially affected by chloroethylclonidine only in human and rat prostate membranes, whereas this agent proved practically devoid of activity in rabbit and dog prostate membranes as well as in the prostatic urethra membranes of all the animal species examined. These findings indicate that in prostatic and urethral membranes the alpha 1-adrenoceptors mainly belong to the alpha 1A subtype. The binding results were confirmed by in vitro functional studies on noradrenaline-induced contractions of rabbit and dog urethral preparations. The agonist-induced contractions were practically unaffected by preincubation of both tissues with chloroethylclonidine, but were sensitive to nifedipine. We found, moreover, a good correlation between the potency of different selective and non-selective alpha 1-adrenoceptor antagonists (WB-4101, 5-methylurapidil, phentolamine, spiperone, prazosin and urapidil) tested against the noradrenaline-induced contractions of rabbit urethra and their affinity for the alpha 1A-adrenoceptor subtype, no correlation with the affinity for the alpha 1B subtype, and a lower correlation with the affinity for the alpha 1C-adrenoceptor subtype.

Adrenergic alpha-Antagonists↗
PubMed1993

Acute noise stress reduces [3H]5-hydroxytryptamine uptake in rat brain synaptosomes: protective effects of buspirone and tianeptine.

Acute noise stress decreased [3H]5-hydroxytryptamine ([3H]5-HT) uptake in synaptosomes from rat hypothalamus, hippocampus and cerebral cortex. The decrease was due to the maximum rate of [3H]5-HT uptake, which peaked 30 min after stress and partly returned to resting values within 4 h, with no changes in affinity (Km values). No changes in [3H]paroxetine binding and basal [3H]5-HT release were found in stressed rats. Tianeptine, given at the dose of 10 mg/kg 1 h before stress, counteracted the noise-induced decrease of 5-HT uptake, since it increased [3H]5-HT uptake in both resting and stressed animals, but did not prevent the rise in plasma corticosterone of stressed rats. Buspirone pretreatment had no effect on [3H]5-HT uptake in resting rats but prevented the noise-induced decrease in [3H]-HT uptake. Diazepam did not modify either the basal or the noise-induced reduction in [3H]5-HT uptake. The evidence that treatments reducing extrasynaptic 5-HT, by increasing its reuptake (tianeptine) or reducing its release (buspirone) in innervated regions are able to modify the stress-induced decrease in 5-HT uptake, further confirms the importance of serotonin in the mechanisms mediating neurochemical responses to stress.

Analysis of Variance↗
PubMed1993

Anorectic effect and brain concentrations of D-fenfluramine in the marmoset: relationship to the in vivo and in vitro effects on serotonergic mechanisms.

The present study investigated the anorectic activity of d-fenfluramine (d-F) and the relationship with brain levels of unchanged drug and its metabolite d-norfenfluramine (d-NF) in marmosets, relating them to neurochemical effects on the serotoninergic system. d-F and d-NF were equally active in reducing food intake (ED50 about 3 mg/kg, p.o.). However, the brain concentrations of the metabolite required to reduce food intake after synthetic d-NF were more than twice those after d-F, indicating that d-NF contributes to but does not completely explain the anorectic effect of d-F. At this dose d-F did not appreciably modify the serotonin (5-HT) and 5-hydroxyindoleacetic (5-HIAA) contents of the brain regions examined, except for a slight enhancement of 5-HIAA in hippocampus. In vitro in brain cortical synaptosomes d-F inhibited [3H]5-HT uptake more potently than d-NF, as in other species. d-F and d-NF showed similar potency in stimulating [3H]5-HT release, in a Ca++ dependent manner. The tritium released by d-F and d-NF appeared to be mainly unmetabolized [3H]5-HT. Like in other species the marmoset too has saturable and specific [3H]d-F binding sites, for which d-NF has lower affinity. d-F and d-NF have low affinities for 5-HT receptor subtypes, except that d-NF has appreciable affinity for 5-HT1C and 5-HT1D receptors. Unlike in rodents but similarly to primates in the striatum the pharmacology of 5-HT receptors seems to correspond to the 5-HT1D subtype.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Affinity of different alpha 1-agonists and antagonists for the alpha 1-adrenoceptors of rabbit and rat liver membranes.

In membranes prepared from rabbit liver, competition with [3H]prazosin by different alpha 1-agonists and antagonists revealed different affinities in comparison to the results obtained on rat liver membranes, and showed a good correlation with the affinity of the same compounds for the cloned alpha 1c-adrenoceptor subtype. The potencies observed on rat liver membranes were well correlated with the affinity observed for the cloned alpha 1b-adrenoceptors. These results confirm that rabbit and rat liver membranes preparations can be utilized to evaluate the affinity of compounds for these alpha 1-adrenergic subtypes.

Adrenergic alpha-Agonists↗
PubMed1993

In-vivo binding of (+)-[3H]PN 200-110 to peripheral tissues and brain of spontaneously hypertensive rats: effect of lacidipine.

The time-course of dihydropyridine receptor occupancy by lacidipine and its relationship with pharmacological activity has been studied in spontaneously hypertensive rat (SHR), as measured by the inhibition of specific (+)-[3H]PN 200-110 binding in-vivo. After oral administration of doses active in reducing blood pressure, lacidipine did not show tissue target differences in respect to binding sites labelled by (+)-[3H]PN 200-110 in cerebral cortex, heart, ileum, bladder and thoracic aorta. The relative occupancy of receptors in heart 60 min after oral administration of 1 mg kg-1 lacidipine was 75%. After 12 h, when lacidipine was still effective in reducing blood pressure in SHR, a low (15%) but detectable proportion of receptors was still occupied by the drug. The percentage decrease of blood pressure was linear with the percentage of receptor occupancy obtained by different doses of lacidipine; that is, there was a close correspondence between ED25 for decrease in blood pressure (0.33 mg kg-1) and ED25 for inhibition of (+)-[3H]PN 200-110 specific binding in the heart (0.36 mg kg-1). The long-lasting effect of lacidipine on blood pressure might be explained by its selective interaction with dihydropyridine binding sites labelled in-vivo by (+)-[3H]PN 200-110.

Administration, Oral↗
PubMed1991

Comparative studies on the anorectic activity of d-fenfluramine in mice, rats, and guinea pigs.

The present study compares the anorectic activity of d-fenfluramine and its metabolite d-norfenfluramine in three animal species. d-Fenfluramine and d-norfenfluramine show anorectic activity at increasing doses (ED50) in rats, guinea pigs, and mice, d-norfenfluramine being more active than d-fenfluramine in all three species. Equiactive anorectic activities are reached with different brain levels of d-fenfluramine and d-norfenfluramine, guinea pigs being the most sensitive species, followed by rats then mice. The metabolite most probably plays a major role in the anorectic effect of d-fenfluramine in guinea pigs, contributes to the anorectic activity in rats, but adds little to the action of the parent drug in mice. The different sensitivity to d-fenfluramine and d-norfenfluramine in these three species does not appear to be explained by a number of biochemical parameters, including serotonin uptake or release, receptor subtypes, or 3H-d-fenfluramine binding and uptake.

Animals↗
PubMed1991

Effects of complete denture wearing on temporomandibular joints: a histomorphometric study.

At autopsy, 54 human temporomandibular joints were distributed in three groups. The first group was made up of 14 joints of dentate subjects (mean age = 51 years). The second group was composed of 12 temporomandibular joints of totally edentulous patients who had lost their teeth for at least 10 years (mean age = 82 years). The third group was composed of 28 joints of edentulous patients who had been wearing complete dentures for at least 20 years (mean age = 66 years). Sagittal serial decalcified sections were studied by light microscopy and was submitted to histomorphometry. Group 1 was characterized by a deep mandibular fossa with well-marked cortical layers of the temporal bones and the condyles. The fibrocartilages were multilayered and the articular disks had biconcave outlines. In group 2 a flattening of the mandibular fossa was observed, with a thinning of the cortical and spongy bones. The fibrocartilages were thin and not multilayered. In group 3, the structure of joints was similar to that of group 1. The mean values of the surfaces, thicknesses, and lengths of the measured parameters were systematically highest in group 1, whereas these mean values in group 3 were similar to or had a tendency to be close to the means of group 1. In contrast, the mean values of group 2 were always the lowest. It can be concluded that complete dentures had a favorable protective effect on temporomandibular joint structures.

Adult↗
PubMed1990

Structural modifications of the nuclear components during lizard oogenesis in relation to the differentiation of the follicular epithelium.

This paper deals with an electron microscope study of nucleolar ultrastructural modifications that occur in the oocytes of the lizard Podarcis sicula during ovarian follicle differentiation. In small diplotene oocytes around which a monolayered follicular epithelium forms, the nucleolus appears as a fibrillo-granular structure. Afterwards, simultaneously with the beginning of pyriform cell differentiation inside the granulosa, the nucleolus progressively condenses and breaks into fragments, forming dense spherical bodies. In larger follicles, with well differentiated pyriform cells, a typical nucleolus is no longer detectable in the oocyte nucleus. These ultrastructural modifications suggest a possible impairment of the oocyte nucleolus in ribosome organization. A possible involvement of pyriform cells in supplying ribosomes to the growing oocyte is discussed.

Animals↗
PubMed1990

In-vivo radiolabelled oxiracetam binding to rat brain.

The in-vivo binding of [3H]oxiracetam has been studied in brain areas of rats examined 30 min after i.c.v. injection. Soluble radioactivity accounted for more than 90% of total radioactivity in all the structures considered and was not affected by co-injection with a 1000-fold excess of unlabelled oxiracetam. Both total and bound radioactivity showed a marked regional distribution, with highest concentrations in the septum, followed by the hippocampus; the cerebral cortex, striatum and cerebellum had the lower concentrations of radioactivity. Computer-assisted quantitative autoradiography with [14C]oxiracetam confirms these findings. Analysis of [3H]oxiracetam bound to membranes indicated that, after co-injection with a 1000-fold excess of unlabelled oxiracetam, there was a significant reduction of binding only in the septum, hippocampus and cerebral cortex. These results suggest that in those cerebral structures oxiracetam binds to saturable sites.

Animals↗
PubMed1989

In-vivo (+)-[3H]fenfluramine binding to rat brain: biochemical and autoradiographic studies.

The in-vivo binding of (+)-[3H]fenfluramine to rat brain regions is saturable, as shown by the inhibition curves obtained by co-injecting increasing concentrations of unlabelled (+)-fenfluramine: at 2.5 mg kg-1 the inhibition of total bound radioactivity was maximal in all regions. The regional distribution of (+)-[3H]fenfluramine specific binding sites (hypothalamus greater than striatum = cortex greater than brainstem greater than hippocampus greater than cerebellum) closely parallels the regional distribution of 5-hydroxytryptamine uptake. Computer-assisted quantitative autoradiography confirms these findings. The IC50 of (+)-fenfluramine for inhibition of its binding in-vivo is below 0.25 mg kg-1, compatible with the presence of high affinity sites. While the physiological role of (+)-[3H]fenfluramine binding sites in the brain, particularly in hypothalamic nuclei, is being investigated, it has been found that in-vivo labelling could also be obtained in the periphery, in lung and renal cortex. The possibility that this peripheral binding is due to the presence of blood platelets cannot be ruled out.

Animals↗
PubMed1988

Different components of 3H-imipramine binding in rat brain membranes: relation to serotonin uptake sites.

In the present paper we confirm and extend previous studies showing heterogeneous 3H-imipramine (3H-IMI) binding sites. Inhibition curves of various drugs (serotonin, imipramine, desmethyl-imipramine, d-fenfluramine, d-norfenfluramine and indalpine, a potent serotonin uptake inhibitor) obtained using 2 nM 3H-IMI and in presence of 120 mM NaCl, confirmed the presence of at least three 3H-IMI binding sites: two of these (high and low affinities) were serotonin-insensitive while the third one was selectively inhibited by serotonin and indalpine with nanomolar affinities. Moreover, this last component was found to be selectively modulated by chronic imipramine treatment thus suggesting a closer relation to serotonin uptake mechanism. These data indicate that the use of a more selective inhibitors of the serotonin-sensitive component (like indalpine or serotonin itself) to define non specific 3H-IMI, may be of help in understanding its relation with serotonin uptake system.

Animals↗