The aim of the present study was to evaluate the performance of whole-body diffusion-weighted imaging (WB-DWI), whole-body positron emission tomography with computed tomography (WB-PET/CT), and whole-body positron emission tomography with magnetic resonance imaging (WB-PET/MRI) in staging patients with untreated invasive ductal carcinoma of the breast. Fifty-one women with newly diagnosed invasive ductal carcinoma of the breast underwent WB-DWI, WB-PET/CT and WB-PET/MRI before treatment. A radiologist and a nuclear medicine physician reviewed in consensus the images from the three modalities and searched for occurrence, number and location of metastases. Final staging, according to each technique, was compared. Pathology and imaging follow-up were used as the reference. WB-DWI, WB-PET/CT and WB-PET/MRI correctly and concordantly staged 33/51 patients: stage IIA in 7 patients, stage IIB in 8 patients, stage IIIC in 4 patients and stage IV in 14 patients. WB-DWI, WB-PET/CT and WB-PET/MRI incorrectly and concordantly staged 1/51 patient as stage IV instead of IIIA. Discordant staging was reported in 17/51 patients. WB-PET/MRI resulted in improved staging when compared to WB-PET/CT (50 correctly staged on WB-PET/MRI vs. 38 correctly staged on WB-PET/CT; McNemar's test; p<0.01). Comparing the performance of WB-PET/MRI and WB-DWI (43 correct) did not reveal a statistically significant difference (McNemar test, p=0.14). WB-PET/MRI is more accurate in the initial staging of breast cancer than WB-DWI and WB-PET/CT, however, the discrepancies between WB-PET/MRI and WB-DWI were not statistically significant. When available, WB-PET/MRI should be considered for staging patient with invasive ductal breast carcinoma.

It has been documented that β-adrenergic antagonists can influence platelet aggregation by a mechanism independent of their ability to antagonize β-adrenoceptors. Nebivolol, a selective β 1 -adrenergic receptor antagonist with additional hemodynamic effects, is able to vasodilate human forearm vasculature by acting on the l -arginine/nitric oxide pathway. Constitutive nitric oxide synthase is present also in human platelets, resulting in the formation of nitric oxide, an endogenous inhibitor of platelet aggregation. The aim of this study was to investigate the effects of nebivolol on platelet aggregation and in particular to determine the involvement of the platelet l -arginine/nitric oxide pathway. Propranolol, a nonselective β-adrenergic antagonist, and carvedilol, a β-blocker with vasodilating properties, were compared with nebivolol on platelet activity. Plasma from healthy male subjects was used. Platelet aggregation was achieved with adenosine diphosphate (ADP) (3 μM) and collagen (1 μg/ml), using the Born turbidimetric method to measure platelet aggregation. Our results showed that nebivolol, propranolol, and carvedilol all had an inhibitory effect on both ADP- and collagen-induced platelet aggregation. Nebivolol exhibited the greatest inhibition effect on platelet aggregation. The mechanism responsible for the inhibitory effect of nebivolol appeared to involve a nitric oxide–dependent pathway. Indeed, l -arginine augmented the inhibitory effects of nebivolol on platelet aggregation induced by collagen and ADP. Furthermore, the inhibitory effect of nebivolol on platelet aggregation was reduced in the presence of the nitric oxide synthase inhibitor N G -monomethyl- l -arginine ( l -NMMA). In conclusion, we have demonstrated in this study that nebivolol's mechanism of platelet aggregation inhibition differs from that of other β-adrenergic antagonists by being partially dependent on nitric oxide production.

Nociceptin/orphanin FQ (N/OFQ), the endogenous ligand for the N/OFQ peptide receptor (NOP), inhibits tachykinin release in the airway of several animal models. The aim of this study was to investigate the role of the N/OFQ–NOP receptor system in bronchoconstriction induced by sensory nerve activation in the isolated mouse lung. We used C57BL/6J NOP+/+, NOP−/−, and Balb/C mice sensitized (or not) to ovalbumin. Bronchopulmonary function coupled with measurements of endogenous N/OFQ levels before and after capsaicin-induced bronchoconstriction in the presence or absence of NOP-selective agonists/antagonists are presented. N/OFQ significantly inhibited capsaicin-induced bronchoconstriction in both naive and sensitized mice, these latter animals displaying airway hyperresponsiveness to capsaicin. The inhibitory effect of N/OFQ were not observed in NOP−/− mice, and were mimicked/abolished by the selective NOP agonist/antagonist University of Ferrara Peptide (UFP)-112/UFP-101 in NOP+/+ mice. UFP-101 alone potentiated the effect of capsaicin in naive mice, but not in sensitized mice. Endogenous N/OFQ levels significantly decreased in sensitized mice relative to naive mice. We have demonstrated that a reduction in endogenous N/OFQ, or the lack of its receptor, causes an increase in capsaicin-induced bronchoconstriction, implying a role for the N/OFQ–NOP receptor system in the modulation of capsaicin effects. Moreover, for the first time, we document differential airway responsiveness to capsaicin between naive and sensitized mice due, at least in part, to decreased endogenous N/OFQ levels in sensitized mice.