Asistent Medicinskog fakulteta, Katedra Hemija, mr Radmila Pavlović uspešno je završila doktorske studije na biohemijskom odseku Državnog Univerziteta u Milanu, Italija. Doktorsku disertaciju pod naslovom "Oxidative and nitrative stress in pathological events: role of selected biomarkers and related analytical studies" odbranila je 13.12.2007. godine i stekla akademski naziv doktor biohemijskih nauka.

UNIVERSITA’ DEGLI STUDI DI MILANO

Facoltŕ di Medicina e Chirurgia

Dipartimento di Medicina, Chirurgia e Odontoiatria

AO  San Paolo - Polo Universitario, Milano

Dottorato di Ricerca in Biochimica

XX Ciclo, BIO/10

OXIDATIVE AND NITRATIVE STRESS IN
PATHOLOGICAL EVENTS: ROLE OF SELECTED
 BIOMARKERS AND RELATED ANALYTICAL STUDIES

Tutor: Prof. Enzo Santaniello

Coordinatore del dottorato: Prof.ssa Silvia PAGANI

Radmila Pavlović

Anno Accademico 2006/2007.

Abstract 

Aim of study was to evaluate different biomarkers for non-invasive measurement of oxidative/nitrative stress. The nitric oxide (NO) pathway was studied by assaying the arginines profile (L-arg, asymmetric dimethylarginine - ADMA, symmetric dimethylarginine – SDMA) in patients from Intensive Care Unit (ICU). ADMA is an endogenous non selective inhibitor of NO synthase while SDMA competes with L-arg for cellular transport. Dimethylarginines (DMA) and nitrate level as well as variety of biochemical and clinical parameters were determined after patients enrolment and during ICU stay. Obtained results suggests that DMA could have a metabolic role tightly related to the development of systemic inflammatory reaction. High DMA levels demonstrates an impaired L-arginine/NO pathway and could promote oxidative stress development. The possibility that DMA may not only indicate risk but rather contribute to adverse events actually opens new therapeutic perspectives. Contemporary, another biomarker of oxidative/nitrative stress has been studied that is 3-nitrotyrosnine (NY).  Up to now, there is no consensus on its basal levels, or on its biological significance. Therefore, a new, gas chromatography–electron capture detector method for plasma free NY has been developed. This new approach provides a readily applicable method for study of the role NY during oxidative/nitrative stress development. Furthermore, there is increasing evidence that carbonyl compounds, and in particular 4-hydroxy-2-nonenal (HNE) generated endogenously during the oxidative degradation of lipids, is involved in the onset and progression of many pathologies. Therefore we  have synthesied 4-hydroxy-2-nonenal dimethylacetal (HNE-DMA) as source of HNE. The synthetic procedure for the preparation of HNE-DMA was adapted to the preparation of a deuterated isotopomer. In this way, a labeled compound could constitute a suitable internal standard for gas chromatography-mass spectrometry (GC-MS) analysis of suitable HNE derivatives.

 

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Datum poslednje izmene: 18.06.2009.god.

Sajt održava: Sunčica Stanković

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