[Show abstract][Hide abstract] ABSTRACT: Abstract The objective of our study was to evaluate the capability of the metabolomics approach to identify the variations of urine metabolites over time related to the neonatal fungal septic condition. The study population included a clinical case of a preterm neonate with invasive fungal infection and 13 healthy preterm controls. This study showed a unique urine metabolic profile of the patient affected by fungal sepsis compared to urine of controls and it was also possible to evaluate the efficacy of therapy in improving patient health.
Journal of Maternal-Fetal and Neonatal Medicine 10/2014; 27 Suppl 2(S2):34-8. DOI:10.3109/14767058.2014.954787 · 1.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Fibromyalgia Syndrome (FMS) is a chronic disease characterized by widespread pain, and difficult to diagnose and treat. We analyzed the plasma metabolic profile of patients with FMS by using a metabolomics approach combining Liquid Chromatography-Quadrupole-Time Of Flight/Mass Spectrometry (LC-Q-TOF/MS) with multivariate statistical analysis, aiming to discriminate patients and controls. LC-Q-TOF/MS analysis of plasma (FMS patients: n = 22 and controls: n = 21) identified many lipid compounds, mainly lysophosphocholines (lysoPCs), phosphocholines and ceramides. Multivariate statistical analysis was performed to identify the discriminating metabolites. A protein docking and molecular dynamic (MD) study was then performed, using the most discriminating lysoPCs, to validate the binding to Platelet Activating Factor (1-alkyl-2-acetyl-sn-glycero-3-phosphocholine, PAF) Receptor (PAFr). Discriminating metabolites between FMS patients and controls were identified as 1-tetradecanoyl-sn-glycero-3-phosphocholine [PC(14∶0/0∶0)] and 1-hexadecanoyl-sn-glycero-3-phosphocholine [PC(16∶0/0∶0)]. MD and docking indicate that the ligands investigated have similar potentialities to activate the PAFr receptor. The application of a metabolomic approach discriminated FMS patients from controls, with an over-representation of PC(14∶0/0∶0) and PC(16∶0/0∶0) compounds in the metabolic profiles. These results and the modeling of metabolite-PAFr interaction, allowed us to hypothesize that lipids oxidative fragmentation might generate lysoPCs in abundance, that in turn will act as PAF-like bioactivators. Overall results suggest disease biomarkers and potential therapeutical targets for FMS.
PLoS ONE 09/2014; 9(9):e107626. DOI:10.1371/journal.pone.0107626 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Carbonyl groups are known to form covalent adducts with endogenous proteins, but so far, their nematicidal mechanism of action of has been overlooked. The nematicidal activity of ten lactones was tested in vitro against the root knot nematodes Meloidogyne incognita and Meloidogynearenaria. In particular, the saturated lactones α-methylene-γ-butyrolactone or tulipaline A (1) and γ-butyrolactone (3) were active against M. incognita with an EC50/48h of 19.3±10.0 and 40.0±16.2mg/L respectively. Moreover the α, β-unsaturated lactone 5,6-dihydro-2H-pyran-2-one (2) exhibited the strongest nematicidal activity against the two species with EC50/48h 14.5±5.3 and 21.2±9.7mg/L respectively. Here we propose that the toxic effects of lactones and aldehydes on M.incognita and M. arenaria might be a consequence of their vacuolar-type H(+)-ATPase (V-ATPase) inhibition activity; in fact α-methylene-γ-butyrolactone (1) and salicylaldehyde (12) produced an increased pH in lysosomal-like organelles on HeLa human cell line and this alteration was most likely related to a V-ATPase impairment.
[Show abstract][Hide abstract] ABSTRACT: Metabolomics, the latest “omics” technology aims to study the complete set of low molecular weight metabolites that may change according to the physiological or pathological state of the organism. Clinical studies dealing with metabolomics in neonatal and pediatric nephrology are very few. In this paper we present the experimental studies in newborn animal models, together with available data on human newborns. Finally the urine metabolomic profiling of 3 newborns who suffered from severe perinatal asphyxia and were treated with hypothermia. They are located in a different part of the multivariate space, the reason of the differences being the basal metabolic profile (resilience) of each neonate: 1 died and 2 survived (one of them developed an acute kidney injury). The main metabolites responsible of the different metabolic profile among the 3 newborns are presented. In the future each neonatologist and nephrologist should become skilled in the metabolomic field.
[Show abstract][Hide abstract] ABSTRACT: The purpose of this article is to study one of the most significant causes of neonatal morbidity and mortality: neonatal sepsis. This pathology is due to a bacterial or fungal infection acquired during the perinatal period. Neonatal sepsis has been categorized into two groups: early onset if it occurs within 3-6 days and late onset after 4-7 days. Due to the not-specific clinical signs, along with the inaccuracy of available biomarkers, the diagnosis is still a major challenge. In this regard, the use of a combined approach based on both nuclear magnetic resonance ((1)H-NMR) and gas-chromatography-mass spectrometry (GC-MS) techniques, coupled with a multivariate statistical analysis, may help to uncover features of the disease that are still hidden. The objective of our study was to evaluate the capability of the metabolomics approach to identify a potential metabolic profile related to the neonatal septic condition. The study population included 25 neonates (15 males and 10 females): 9 (6 males and 3 females) patients had a diagnosis of sepsis and 16 were healthy controls (9 males and 7 females). This study showed a unique metabolic profile of the patients affected by sepsis compared to non-affected ones with a statistically significant difference between the two groups (p = 0.05).
Early human development 03/2014; 90 Suppl 1:S78-83. DOI:10.1016/S0378-3782(14)70024-6 · 1.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The nematicidal activity of selected aromatic aldehydes was tested against the root knot nematode Meloidogyne incognita. The most active aldehyde was phthalaldehyde with an EC50 value of 10.59 ± 5.95 mg/L followed by salicylaldehyde and cinnamic aldehyde with an EC50 of 10.80 ± 0.99 and 12.12 ± 5.28 mg/L respectively. On the other hand, structurally related aldehydes such us 2-methoxybenzaldehyde, 3,4-dimethoxybenzaldehyde and vanillin were not active at the concentration of 1000 mg/L. By liquid chromatography mass spectrometry the reactivity of tested aldehydes against a synthetic peptide resembling the nematode cuticle was characterized. We report that at the test concentration of 1 mM, the main adduct formation was observed for 3,4-diihydroxybenzaldehyde, 2-methoxybenzaldehyde, 3,4-dimethoxybenzaldehyde Considering that 2-methoxybenzaldehyde and 3,4-dimethoxybenzaldehyde were not active against M. incognita in in vitro experiments lead us to hypothesize a different mechanism of action rather than an effect on the external cuticle modification of nematodes. When the toxicity of the V-ATPase inhibitor pyocyanin was tested against M. incognita J2 nematodes an EC50 at 24 h of 72.1 ± 25.3 mg/L was found. This toxicity was comparable with those redox-active compounds such us salicylaldehyde and phthalaldehyde suggesting a common mode of action inhibiting nematode V-ATPase enzyme. The results of this investigation reveal that aromatic redox-active aldehydes can be considered as potent nematicides, and further investigation is needed to completely clarify their mode of action.
Journal of Agricultural and Food Chemistry 02/2013; 61(8). DOI:10.1021/jf305164m · 2.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: New pesticides based on plant extracts have recently gained interest in the development of nontoxic crop protection chemicals. Numerous research studies are focused on the isolation and identification of new active compounds derived from plants. In this manuscript we report about the use of the Mediterranean species Capparis spinosa as a potent natural nematicidal agent against the root knot nematodes Meloidogyne incognita. Leaves, stems, and caper buds of Capparis spinosa were used to obtain their methanol extracts (LME, SME, BME) that were successively in vitro tested against second stage nematode juveniles (J2). In terms of paralysis induction, the methanol extract of the stem part (SME) was found more effective against M. incognita and then the caper methanol buds and leaves extracts. The chemical composition analysis of the extracts carried out by GC/MS and LC/MS techniques showed that methylisothiocyanate was the main compound of SME. The EC(50) for SME after 3 days of immersion was 215 ± 36 mg/L. The constituent components of SME such as 2-thiophenecarboxaldehyde and methylisothiocyanate were successively in vitro tested for their nematicidal activity against J2. Both compounds induced paralysis on root knot nematodes ranking first (EC(50) = 7.9 ± 1.6, and 14.1 ± 1.9 mg/L respectively) for M. incognita. Moreover, 2-thiophenecarboxaldehyde showed a strong fumigant activity.
Journal of Agricultural and Food Chemistry 07/2012; 60(30). DOI:10.1021/jf302075w · 2.91 Impact Factor