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2. Modellazione del flusso sanguigno in reti di vasi viscoelastici

Author

Piccioli, F, Bertaglia, G, Valiani, A, and Caleffi, V

Subjects
PE3_14, Trattazione delle giunzioni e delle condizioni al contorno per reti a comportamento viscoelastico, PE8_5, Reti circolatorie arteriose e venose, Comportamento viscoelastico dei vasi sanguigni, Trattazione delle giunzioni e delle condizioni al contorno per reti a comportamento viscoelastico, Cappio di isteresi pressione-area, PE1_18, Reti circolatorie arteriose e venose, Comportamento viscoelastico dei vasi sanguigni, NO, Cappio di isteresi pressione-area
Published
2021

6. Biological role of adduct formation of the ruthenium(III) complex NAMI-A with serum albumin and serum transferrin

Author

Francesca Piccioli, Luigi Messori, Moreno Cocchietto, A. Bergamo, Gianni Sava, Bergamo, A, Messori, L, Piccioli, F, Cocchietto, M, Sava, G, and Sava, Gianni

Subjects
Cell Survival, Serum albumin, Mice, chemistry.chemical_compound, Antigens, CD, In vivo, Cell Line, Tumor, Receptors, Transferrin, Organometallic Compounds, Animals, Humans, NAMI-A, Dimethyl Sulfoxide, Pharmacology (medical), Serum Albumin, Pharmacology, chemistry.chemical_classification, biology, Transferrin, Albumin, Biological activity, Xenograft Model Antitumor Assays, Blood proteins, In vitro, Antigens, Differentiation, B-Lymphocyte, Oncology, chemistry, Biochemistry, Mice, Inbred CBA, biology.protein, Ruthenium Compounds, Female, Protein Binding
Abstract

NAMI-A is an innovative ruthenium(III) complex with a very encouraging preclinical profile of metastasis inhibition, which is undergoing initial phases of clinical trials. To assess the pharmacological relevance of the drug fraction associated to plasma proteins, adducts of NAMI-A with either serum albumin or serum transferrin were prepared and their biological effects tested in vitro and in vivo. Specifically, adducts of NAMI-A with either serum albumin or serum transferrin, prepared and characterized at a ruthenium-to-protein molar ratio of 4:1, were evaluated in vitro on the KB human tumor cell line and in vivo on the MCa mammary carcinoma tumor. The effects of NAMI-A/protein adducts on cell viability and on cell cycle progression were found to be far smaller than those produced by free NAMI-A. GFAAS measurements point out that the amount of ruthenium that gets into cells is drastically reduced when NAMI-A is presented in its protein-bound form. In vivo use of NAMI-A adducts with albumin and transferrin resulted markedly less effective on lung metastasis reduction, than free NAMI-A. Overall, the present results suggest that binding to plasma proteins causes a drastic decrease of NAMI-A bioavailability and a subsequent reduction of its biological activity, implying that association to plasma proteins essentially represents a mechanism of drug inactivation.

Published
2003

9. Cardiac contractility is a key factor in determining pulse pressure and its peripheral amplification.

Author

Piccioli F, Li Y, Valiani A, Caleffi V, Chowienczyk P, and Alastruey J

Abstract

Background: Arterial stiffening and peripheral wave reflections have been considered the major determinants of raised pulse pressure (PP) and isolated systolic hypertension, but the importance of cardiac contractility and ventricular ejection dynamics is also recognised., Methods: We examined the contributions of arterial compliance and ventricular contractility to variations in aortic flow and increased central (cPP) and peripheral (pPP) pulse pressure, and PP amplification (PPa) in normotensive subjects during pharmacological modulation of physiology, in hypertensive subjects, and in silico using a cardiovascular model accounting for ventricular-aortic coupling. Reflections at the aortic root and from downstream vessels were quantified using emission and reflection coefficients, respectively., Results: cPP was strongly associated with contractility and compliance, whereas pPP and PPa were strongly associated with contractility. Increased contractility by inotropic stimulation increased peak aortic flow (323.9 ± 52.8 vs. 389.1 ± 65.1 ml/s), and the rate of increase (3193.6 ± 793.0 vs. 4848.3 ± 450.4 ml/s 2 ) in aortic flow, leading to larger cPP (36.1 ± 8.8 vs. 59.0 ± 10.8 mmHg), pPP (56.9 ± 13.1 vs. 93.0 ± 17.0 mmHg) and PPa (20.8 ± 4.8 vs. 34.0 ± 7.3 mmHg). Increased compliance by vasodilation decreased cPP (62.2 ± 20.2 vs. 45.2 ± 17.8 mmHg) without altering d P / d t , pPP or PPa. The emission coefficient changed with increasing cPP, but the reflection coefficient did not. These results agreed with in silico data obtained by independently changing contractility/compliance over the range observed in vivo ., Conclusions: Ventricular contractility plays a key role in raising and amplifying PP, by altering aortic flow wave morphology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Piccioli, Li, Valiani, Caleffi, Chowienczyk and Alastruey.)

Published
2023
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