L'emozione di marmo. I monumenti ai caduti della Grande Guerra a Pisa e nel territorio

Catalogo della mostra omonima presso il Museo della Grafica - Palazzo Lanfranchi, Pisa, 16 luglio-4 novembre 2015

L'emozione di marmo

Introduzione al catalogo della mostra tenutasi al Museo della Grafia - Palazzo Lanfranchi, Pisa, dal 16 luglio al 4 novembre 201

Synthesis and in-vitro antitumour activity of new naphthyridine derivatives on human pancreatic cancer cells

Objectives The aim of the study was to evaluate the antitumour effect in vitro of newly synthesized 7-substituted-2,3-dihydro-1,8-naphthyridines. Methods Characterization tools included cell viability assay, caspase 3/7 induction, DNA fragmentation, fibroblastic growth factor type 1 receptor kinase inhibition, and in-vitro antiangiogenic analysis. Key findings Treatment of MIA PaCa-2 human pancreatic cancer cells with test compounds showed time- and concentration-dependent cytotoxicity with IC50 values in the micromolar range. Compounds with an aminoalkyl or a diaminoalkyl side chain at the 7-position exhibited remarkable cytotoxicity, whereas the presence of a methyl group or a cyclic amine in the same position led to a significant decrease in their biological activity. Cytotoxicity screening demonstrated that the most active was compound 11 (mean 50% inhibition of cell proliferation [IC50] 11 mM). This compound had an in-vitro antitumor efficacy superior to 5-fluorouracil (the lowest cell viability value after treatment [Emax] 0.2% and 19%, respectively) and proved to be less toxic than 5-fluorouracil against noncancerous human oral epithelial cells. In addition, compound 11 induced apoptosis in MIA PaCa-2 cells and it was able to promote antiangiogenic effects in vitro. Finally, its cytotoxicity was enhanced in pancreatic cancer cells stimulated with fibroblastic growth factor, while no substantial effect was observed on human bronchial smooth muscle cells stimulated with the same growth factor. Conclusions These findings suggest that 1,8-naphthyridine derivatives are a promising class of compounds in cancer research. In particular, the antitumor activity of compound 11 is worth further investigation

Doctoral courses (in geotechnical engineering): What has been changing in Italy in the last 30 years

Doctoral schools in Italy began on middle 80s. Since that the objectives and fundamental rules for the third level of Higher Education in Italy changed several times. The paper shows the legislative evolution and reports, in a narrative way, the experience of 5 Ph. D. in Geotechnical Engineering over a period of 30 years (from 1987 to 2017). The narration focuses on general rules, availability of grants, tutorage and evaluation board, pointing out positive and negative aspects of the many changes occurred over 30 years. Ph. D. Courses in Italy are regulated by National Laws approved by the Parliament. The main conclusions can be summarized as follows: a) the recently introduced requirement of educational credits acquisition did not change the spirit of Doctoral studies that are mainly oriented to strength the students' research skills; b) based on the Authors' experiences it is strongly advised to promote Doctoral Schools restricted to specific subject areas in which the teaching staff and the members of the Council belong from different institutions (Consortia); c) Bilateral Agreements for double or multiple degrees are really encouraged

The sulfaphenazole-sensitive pathway acts as a compensatory mechanism for impaired nitric oxide availability in patients with primary hyperparathyroidism. Effect of surgical treatment

Objective: The aim of this study was to assess whether patients with primary hyperparathyroidism (PHPT) show reduced endothelial function and to determine the mechanisms involved. The impact of parathyroidectomy (PTx) on endothelial function was also assessed. Background: Endothelial dysfunction is reported in patients with PHPT, but the mechanisms involved are unknown. Methods: We evaluated forearm blood flow changes (strain gauge plethysmography) induced by intraarterial acetylcholine or sodium nitroprusside in 17 PHPT women and 17 age-matched controls. Nitric oxide (NO) availability and oxidative stress were studied by repeating acetylcholine during intraarterial infusion of L-N(G)-monomethyl arginine (L-NMMA, a NO synthase inhibitor) and ascorbic acid (an oxidative stress scavenger). The role of cytochrome P450 epoxygenase (CYP 2C9)-derived endothelium-derived hyperpolarizing factor (EDHF) was assessed by repeating acetylcholine under intraarterial sulfaphenazole. In six PHPT patients, the study was repeated 12 months after successful PTx. Results: Responses to sodium nitroprusside and acetylcholine were similar in PHPT patients and controls. L-NMMA inhibited the response to acetylcholine in controls (P < 0.001), whereas it had no effect in PHPT patients. In both groups, ascorbic acid failed to affect acetylcholine. Sulfaphenazole administration, although not affecting vasodilation to acetylcholine in controls, blunted the response to acetylcholine in PHPT patients (P < 0.005). After PTx, the inhibitory effect of L-NMMA on acetylcholine was restored (P < 0.001), and the inhibitory effect of sulfaphenazole on acetylcholine was abrogated. Conclusions: PHPT patients show compromised NO availability, whereas oxidative stress generation is not involved. A compensatory CYP 2C9-derived EDHF pathway is activated to sustain endothelium-dependent vasodilation. This PHPT-related endothelial dysfunction is reversed after PTx

The sulfaphenazole-sensitive pathway acts as a compensatory mechanism for impaired nitric oxide availability in patients with primary hyperparathyroidism

OBJECTIVE: The aim of this study was to assess whether patients with primary hyperparathyroidism (PHPT) show reduced endothelial function and to determine the mechanisms involved. The impact of parathyroidectomy (PTx) on endothelial function was also assessed. BACKGROUND: Endothelial dysfunction is reported in patients with PHPT, but the mechanisms involved are unknown. METHODS: We evaluated forearm blood flow changes (strain gauge plethysmography) induced by intraarterial acetylcholine or sodium nitroprusside in 17 PHPT women and 17 age-matched controls. Nitric oxide (NO) availability and oxidative stress were studied by repeating acetylcholine during intraarterial infusion of L-N(G)-monomethyl arginine (L-NMMA, a NO synthase inhibitor) and ascorbic acid (an oxidative stress scavenger). The role of cytochrome P450 epoxygenase (CYP 2C9)-derived endothelium-derived hyperpolarizing factor (EDHF) was assessed by repeating acetylcholine under intraarterial sulfaphenazole. In six PHPT patients, the study was repeated 12 months after successful PTx. RESULTS: Responses to sodium nitroprusside and acetylcholine were similar in PHPT patients and controls. L-NMMA inhibited the response to acetylcholine in controls (P < 0.001), whereas it had no effect in PHPT patients. In both groups, ascorbic acid failed to affect acetylcholine. Sulfaphenazole administration, although not affecting vasodilation to acetylcholine in controls, blunted the response to acetylcholine in PHPT patients (P < 0.005). After PTx, the inhibitory effect of L-NMMA on acetylcholine was restored (P < 0.001), and the inhibitory effect of sulfaphenazole on acetylcholine was abrogated. CONCLUSIONS: PHPT patients show compromised NO availability, whereas oxidative stress generation is not involved. A compensatory CYP 2C9-derived EDHF pathway is activated to sustain endothelium-dependent vasodilation. This PHPT-related endothelial dysfunction is reversed after PTx