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Supervisors: Prof. Roger Fuoco, Dr. Fabio Di Francesco
Title: Novel strategies and emerging biomarkers for the management of Patent Ductus Arteriosus in preterm newborns.
Abstract:
The determination of suitably selected and very informative biomarkers in biological fluids that are collected by means of non-invasive procedures represents the holy grail of clinical practice. Oral fluid, breath, urine and Dried Blood Spots (DBS) can represent today a promising complement, and possibly an alternative, to conventional fluids due to almost non-invasiveness, safer handling, easy and painless collection. The use of the aforementioned specimens may be of great interest for the diagnosis and management of preterm newborns suffering from Patent Ductus Arteriosus (PDA), which is one of the most debated issue in modern neonatology. Ductus patency is primarily due to an increased oxygen tension and high prostaglandin-E2 (PGE2) levels, which are suppressed by cyclooxygenase inhibitors (e.g. ibuprofen, acetaminophen). The choice of treatment is challenging as it depends on a complex risks/benefits analysis due to the possible side effects and frequent failures of drugs. Reasons for the unsatisfactory outcome are probably relate to the presence of several relaxing mechanisms concurrent to the PGE2 action, such as the hypothesized vasoactive role of isoprostanes, 8-isoPGF2α and 8-isoPGE2, which are products of the oxidative stress induced by high oxygen tension at birth. The aim of my PhD project is to develop and validate highly sensitive and selective UHPLC-MS/MS methods for the determination of a pattern of biomarkers related to PDA pathophysiology and pharmacological treatment from a single drop of blood or urine sample. In particular, ibuprofen, creatinine and uric acid levels will be measured to monitor the therapeutic treatment and its main side effect (i.e. renal failure), meanwhile prostaglandin and isoprostanes, PGE2, 8-isoPGE2 and 8-isoPGF2α, will be determined to assess their potential role on the lack of responsiveness to ibuprofen administration. Once confirmed their role on ductal patency maintenance, the outcome of the project will be the definition of the corresponding cut off levels for the early identification of non-responders. This should represent a concrete step forward in neonatal clinical practice, aimed at the better comprehension of DA closure mechanisms and the possible identification of predictors of response to therapy that would lead to a personalized medical approach, a decrease of public health costs and risks of unjustified adverse events for patients.
Publications:
- T. Lomonaco, S. Ghimenti, I. Piga, D. Biagini, M. Onor, R. Fuoco, F. Di Francesco. Influence of sampling on the determination of warfarin and warfarin alcohols in oral fluid. PLoS ONE 2014; 9(12): e114430. doi: 10.1371/journal.pone.0114430.
- T. Lomonaco, P. Salvo, S. Ghimenti, D. Biagini, F.G. Bellagambi, R. Fuoco and F. Di Francesco. A breath sampling system assessing the influence of respiratory rate on exhaled breath composition. 37th Annual International Conference of the IEEE (25-29 Agosto 2015), Engineering in Medicine and Biology Society (EMBC) 2015: 7618-21. doi: 10.1109/EMBC.2015.7320156.
Oral communications at congress:
Poster communications at congress:
D. Biagini, T. Lomonaco, S. Ghimenti, F.G. Bellagambi, F. Di Francesco, R. Fuoco. Needle trap micro-extraction: an innovative approach for the one step sampling and pre-concentration of volatile organic compounds in exhaled breath, XXVI Congresso Nazionale della Divisione di Chimica Analitica della Società Chimica Italiana, (18-22 Settembre 2016, Messina, Italia). BEST POSTER AWARD WINNER.