Full Professor
Department of Experimental and Clinical Biomedical Sciences
Via J.H. Dunant 5 – 21100 Varese
Tel:: +39-0332-397104
Fax: +39-0332-397119
E-mail: daniela.negrini@uninsubria.it

1982 - Degree in Biological Sciences with an experimental thesis entitled: "Starling equilibrium and lymphatic drainage at the level of the pleural and peritoneal cavities".

1983 - Receives from the International Union of Physiological Sciences a travel award for European Young Researchers on occasion of the XIX Meeting of the International Union of Physiological Sciences, held in Sydney, Australia.

1984 - Specialized in Biological Research at the University of Milan with an experimental thesis entitled: "Regional differences in pleural liquid pressure and physiological mechanisms involved".

1985 – 1998 Assistant Professor of Physiology at the Institute of Human Physiology, Faculty of Medicine, University of Milan.
1998-2001- Associate Professor of Physiology at the Institute of Human Physiology, Faculty of Medicine, University of Milan

2000 – Visiting Professor, Faculty of Medicine, University of Bergen, Norway.

Since 2001 – Full Professor of Human Physiology, Department of Biomedical Experimental and Clinical Sciences, University of Insubria, Varese, Italy.

Invited as speaker to:

- XXXII Congress of the International Union of Physiological Sciences (I.U.P.S.), Glasgow (1993). Symposium: "Interstitium, connective tissue and lymphatics". Invited by the International Union of Physiological Sciences.

- Annual Fall Meeting of the Biomedical Engeneering Society, Tempe, Arizona, 1994. Session: Pulmonary Mechanics

- First Congress of the Federation of European Physiological Society, Maastrict, 1995. Symposium: "Transendotelial solute and water transport".

- Annual Fall Meeting of the Biomedical Engineering Society. Boston, 1995. Session: Pulmonary Circulation Session.

- New Perspectives in Microvascular Fluid Exchanges, a Hundred Years after Starling, Broadway, Worcestershire, 1996. Session: Fluid exchange with transcellular compartments. Invited by Welcome Trust.

- XXXIII Congress of the International Union of Physiological Sciences (I.U.P.S.), St. Petersburg (1997). Symposium "From Molecules to Humans". Invited by the International Union of Physiological Sciences.

- First Conference: “Acute Respiratory Distress Syndrome: Cellular and Molecular Mechanisms and Clinical Management”. Corfù, 1997, sponsored by the North Atlantic Treaty Organization (NATO) Scientific Affairs Division. Invited by NATO.

- 22nd Meeting of the European Society for Microcirculation, Exeter, UK, 2002

- 18th Postgraduate Course in Critical Care Medicine – Anesthesia, Pain, Intensive Care and Emergency Medicine, A.P.I.C.E., November, 2003.

- Gordon Research Conference “ Molecular Mechanisms in Lymphatic Function and Diseases”, Ventura, CA, USA, Marzo 2004

The extracellular interstitial space (ECM) is the structural framework to the cellular compartment. Its flexible support is provided by large interconnected macromolecules like collagen, elastin, hyaluronan and proteoglycans framing the three-dimensional fibrous architecture of the tissue. In addition, hyaluronan and proteoglycans, because of their high anionic charge, bound water molecules which equilibrate with free interstitial fluid determining tissue hydration.

The latter is an important parameter in guaranteeing tissue function, particularly in some tissues like the lung parenchyma, the pleural space and the brain. Indeed, it is well known that an increase in fluid content, like that observed in pulmonary or cerebral edema or in pleural effusion, may result in highly impaired organ function eventually leading to severe pathology. Interstitial fluid volume is controlled under physiological conditions through the interaction between: a) a minimized fluid filtration across the capillary endothelium; b) a low mechanical compliance of the interstitial tissue matrix; c) an efficient removal of fluid and protein into the initial lymphatic system.

The research activity at the Laboratory of Human Physiology is focused on tissue and lymphatic system physiology, being actually involved the following research lines:

- study of the mechanisms of lymph formation and propulsion in the initial pleural lymphatic system and in the lung by directly measuring interstitial and lymphatic pressure through micropuncture technique in the intact organ

- morphometric description of the initial pleural lymphatic system (using immunohystochemistry; transmission and scanning electron microscopy, confocal fluorescence microscopy, atomic microscopy)

- mathematical and biophysical modeling of lymphatic and interstitial pressure waves

- endothelial and smooth muscle lymphatic cell biology

- physiopatology of the lymphatic system

- physiology and pathophysiology of the pulmonary ECM and microvasculature

1. NEGRINI, D., S. MUKENGE, M. DEL FABBRO, C. GONANO and G. MISEROCCHI. Distribution of diaphragmatic lymphatic stomata. J. Appl. Physiol. 70: 1544-1549, 1991.

2. MISEROCCHI, G. and D. NEGRINI. Pleural lymphatics as regulators of pleural fluid dynamics. In: News in Physiological Sciences, ed. by I.U.P.S. and A.P.S., Vol. 6, pp.153-158, 1991.

3. MISEROCCHI, G., D. NEGRINI and C. GONANO. Parenchymal stress affects interstitial and pleural pressures in in-situ lung. J. Appl. Physiol. 71: 1967-1972, 1991.

4. NEGRINI, D., R.K. REED and G. MISEROCCHI. Permeability-surface area product and reflection coefficient of parietal pleura in dogs. J. Appl. Physiol. 71: 2543-2547, 1991.

5. NEGRINI, D., C. GONANO and G. MISEROCCHI. Microvascular pressure profile in intact in situ lung. J.Appl. Physiol. 72: 332-339, 1992.

6. NEGRINI, D. Is the microvascular resistance large in the lung? J. Appl.Physiol. 73: 2723, 1992.

7. NEGRINI, D., M. DEL FABBRO, C.GONANO, S. MUKENGE and G. MISEROCCHI. Distribution of diaphragmatic lymphatic lacunae. J. Appl. Physiol. 72: 1166-1172, 1992.

8. MISEROCCHI, G., D. VENTUROLI, D. NEGRINI, M.C. GILARDI and R. BELLINA. Intrapleural fluid movements described by a porous flow model. J. Appl. Physiol. 73: 2511-2516, 1992.

9. NEGRINI, D., M.DEL FABBRO and D.VENTUROLI. Fluid exchanges across the parietal peritoneal and pleural mesothelia. J.Appl. Physiol. 74: 1779-1784, 1993.

10. MISEROCCHI, G., D. NEGRINI, M. DEL FABBRO and D. VENTUROLI. Pulmonary interstitial pressure in intact in situ lung: the transition to interstitial edema. J. Appl. Physiol. 74: 1171-1177, 1993.

11. MISEROCCHI, G., D. VENTUROLI, D. NEGRINI , M.DEL FABBRO. Model of pleural fluid turnover. J Appl Physiol 75: 1798-1806, 1993.

12. NEGRINI, D., D.VENTUROLI, M.I.TOWNSLEY and R.K.REED. Permeability of the parietal pleura to liquid and proteins. J.Appl.Physiol. 76: 627-633, 1994.

13. NEGRINI, D., S.T.BALLARD and J.N.BENOIT. Contribution of lymphatic miogenic activity and of respiratory movements to pleural lymph flow. J.Appl.Physiol. 76: 2267-2274, 1994.

14. VENTUROLI, D., B.CRISAFULLI, M.DEL FABBRO, D.NEGRINI and G.MISEROCCHI. Estimation of in-vivo pulmonary microvascular and interstitial geometry using digital image analysis. Microcirculation. 2(1): 1-14, 1995.

15. NEGRINI, D. Pulmonary microvascular pressure profile during development of hydrostatic edema. Microcirculation. 2(2): 1-8, 1995.

16. NEGRINI, D., S.T.BALLARD and J.N.BENOIT. Mechanisms involved in pleural liquid turnover. J.Appl.Physiol. 78 (6): 2329-2330, 1995.

17. NEGRINI, D., A.PASSI, G. DE LUCA and G.MISEROCCHI. Pulmonary interstitial pressure and proteoglycans during development of pulmonary edema. Am.J.Physiol. 270 (Heart Circ. Physiol. 39), 1996.

18. NEGRINI, D., A.PASSI, G.DE LUCA and G. MISEROCCHI. Proteoglycan involvement during development of lesional pulmonary edema. Am.J.Physiol. 274 (Lung Cell.Mol.Physiol. 18): L203-L211, 1998.

19. PASSI, A., D.NEGRINI, R. ALBERTINI, G.DE LUCA and G. MISEROCCHI. Involvement of lung interstitial proteoglycans in development of hydraulic and elastase induced edema. Am.J.Physiol. 275 (Lung Cell.Mol.Physiol. 19), 1998.

20. PASSI, A., D.NEGRINI, R. ALBERTINI, G. MISEROCCHI and G.DE LUCA. The sensitivity of versican from rabbit lung to gelatinase A (MMP-2) and B (MMP-9) and its involvement in the development of hydraulic lung edema. FEBS Letter 456: 93-96, 1999.

21. NEGRINI, D. and M. DEL FABBRO. Subatmospheric pressure in the rabbit pleural lymphatic network. Journal of Physiology, 520.3: 761-769, 1999.

22. NEGRINI, D., A. PASSI, K. BERTIN, F. BOSI and H. WIIG. Isolation of pulmonary interstitial fluid in rabbits by a modified wick technique. Am J Physiol (Lung Cell Mol Physiol 280), L1057-L1065, 2001.

23. MISEROCCHI, G., A. PASSI, D.NEGRINI, M.DEL FABBRO and G.DE LUCA. Pulmonary interstitial pressure and tissue matrix structure in hypoxia. Am J Physiol (Lung Cell Mol Physiol 280), L881-L887, 2001.

24. MISEROCCHI, G., D.NEGRINI, A. PASSI, and G. DE LUCA. Development of lung edema: interstitial fluid dynamics and molecular structure. News in Physiological Sciences, ed. by I.U.P.S. and A.P.S., Vol. 16, pp.66-70, 2001.

25. NEGRINI, D., A. CANDIANI, F. BOSCHETTI, B. CRISAFULLI, M. DEL FABBRO, D. BETTINELLI and G. MISEROCCHI. Pulmonary microvascular and perivascular interstitial geometry during development of mild hydraulic edema. Am J Physiol (Lung Cell Mol Physiol 281), L1464-L1471, 2001.

26. NEGRINI, D., O.TENSTAD, H. WIIG. Interstitial exclusion of albumin in rabbit lung measured with the continuous infusion methods in combination with the wick technique. Microcirculation. 10, 124-136, 2003

27. NEGRINI, D., O.TENSTAD, H. WIIG. Interstitial exclusion of albumin in rabbit lung during development of pulmonary oedema. J Physiol. 548.3, 907-917, 2003.

28. NEGRINI, D., A. MORIONDO, S.MUKENGE. Transmural pressure during cardiogenic oscillations in rodent diaphragmatic lymphatic vessels. Lymphatic Research and Biology, 2(2):-69-81, 2004.

29. MORIONDO A-, S.MUKENGE, D.NEGRINI. Transmural pressure in rat initial subpleural lymphatics during spontaneous or mechanical ventilation. Am. J. Physiol. (Heart and Circulatory System), 289:263-269, 2005

30. NEGRINI, D., O.TENSTAD, A.PASSI, H. WIIG. Differential degradation of matrix proteoglycans and edema development in rabbit lung. Am J Physiol (Lung Cell Mol Physiol). Published as Article in press.