showing 30 related works from this author
Evaluation of the effect of chance correlations on variable selection using Partial Least Squares -Discriminant Analysis
2013
Variable subset selection is often mandatory in high throughput metabolomics and proteomics. However, depending on the variable to sample ratio there is a significant susceptibility of variable selection towards chance correlations. The evaluation of the predictive capabilities of PLSDA models estimated by cross-validation after feature selection provides overly optimistic results if the selection is performed on the entire set and no external validation set is available. In this work, a simulation of the statistical null hypothesis is proposed to test whether the discrimination capability of a PLSDA model after variable selection estimated by cross-validation is statistically higher than t…
Interaction Between Cytokines and Oxidative Stress in Acute Pancreatitis
2006
Acute pancreatitis is an inflammation initially localized in the pancreatic gland which may lead to local and systemic complications. The development of severe acute pancreatitis is mediated by pathophysiological mechanisms involved in the systemic inflammatory response, cytokines and oxidative stress being their components of major importance. Nevertheless, it is still unknown why an episode of acute pancreatitis remains mild or progresses to a severe form. Activated leukocytes are the main source of cytokines. Interleukin 1beta and tumor necrosis factor alpha (TNF-alpha) initiate and propagate almost all the consequences of the systemic inflammatory response syndrome, leading to amplifica…
Electronic nature of the emitting triplet in SF 5 -substituted cationic Ir(III) complexes
2018
Abstract A theoretical density functional theory study has been performed on a family of cationic iridium(III) complexes of the form [Ir(C^N)2(dtBubpy)]+ (dtBubpy = 4,4′-di-tert-butyl-2,2′-bipyridine), that incorporate 2-phenylpyridine (1, 2) and 1-phenylpyrazole (3, 4) cyclometallating C^N ligands functionalized with SF5 groups. The goal is to investigate the effect that the inclusion of SF5 groups in meta (1, 3) and para position (2, 4) with respect to the Ir–C bond has on the electronic nature of the emitting triplet state and the emission wavelength. The attachment of the electron-withdrawing groups induces the stabilization of the molecular orbitals localized on the C^N ligands and, in…
Neuroprotection by targeting antioxidant γ-glutamylcysteine to mitochondria
2012
Metabolic adaptation and neuroprotection differ in the retina and choroid in a piglet model of acute postnatal hypoxia.
2013
Hypoxic-ischemic insults to the neonatal brain may cause neurodevelopmental disorders. Vulnerability of different areas of the neural tissue to hypoxic-ischemic stress might be explained by either heterogeneous sensitivity to oxygen or neuroprotective capability. Our understanding of regional heterogeneity is still incomplete in terms of metabolic reconfiguration and/or activation of neuroprotective mechanisms.We studied, by western blotting, reverse-transcriptase PCR, and tandem mass spectrometry, the response of retina and choroid at protein, gene, and metabolic levels during hypoxia in a piglet model of acute postnatal hypoxia.We evidenced a metabolic shift towards glycolysis in choroid …
Mitochondrial biogenesis fails in secondary biliary cirrhosis in rats leading to mitochondrial DNA depletion and deletions
2011
Chronic cholestasis is characterizedby mitochondrial dysfunction, associated with loss of mitochondrialmembrane potential, decreased activities of respiratory chaincomplexes, and ATP production. Our aim was to determine themolecular mechanisms that link long-term cholestasis to mitochondrialdysfunction. We studied a model of chronic cholestasis inducedby bile duct ligation in rats. Key sensors and regulators of theenergetic state and mitochondrial biogenesis, mitochondrial DNA(mtDNA)-to-nuclear DNA (nDNA) ratio (mtDNA/nDNA) relativecopy number, mtDNA deletions, and indexes of apoptosis (BAX,BCL-2, and cleaved caspase 3) and cell proliferation (PCNA) wereevaluated. Our results show that long…
Expression of aquaporins early in human pregnancy
2011
Abstract Background Aquaporins (AQPs) constitute a family of channel proteins implicated in transmembrane water transport. Thirteen different AQPs (AQP0–12) have been described but their precise biologic function still remains unclear. AQPs 1, 3, 4, 8, and 9 expression has been described in human chorion, amnion and placenta; however, AQP4 is the only that has been identified in the first trimester of human pregnancy. Objective To assess multiplicity of AQPs expression from 10th to 14th week gestation. Population and methods Chorionic villi samples (CVS) collected in pregnant women for prenatal diagnosis were analysed by real time-PCR to assess cDNA expression of AQPs 1, 2, 3, 4, 5, 6, 7, 8…
Obese Rats Exhibit High Levels of Fat Necrosis and Isoprostanes in Taurocholate-Induced Acute Pancreatitis
2012
BACKGROUND: Obesity is a prognostic factor for severity in acute pancreatitis in humans. Our aim was to assess the role of oxidative stress and abdominal fat in the increased severity of acute pancreatitis in obese rats. METHODOLOGY: Taurocholate-induced acute pancreatitis was performed in lean and obese Zucker rats. Levels of reduced glutathione, oxidized glutathione, L-cysteine, cystine, and S-adenosylmethionine were measured in pancreas as well as the activities of serine/threonine protein phosphatases PP1 and PP2A and tyrosin phosphatases. Isoprostane, malondialdehyde, triglyceride, and free fatty acid levels and lipase activity were measured in plasma and ascites. Lipase activity was m…
Disulfide stress and its targets in acute pancreatitis
2014
Under physiological conditions, the balance between ROS production and removal properly maintains the intracellular redox-sensitive signaling as well as the appropriate status of protein thiols and disulfides. However, inflammation among other factors can modify this balance causing a rapid increase in intracellular ROS levels and hence thiol oxidation, eventually leading to oxidative stress. In the case of acute pancreatitis, both redox signaling and oxidative stress seem to contribute to the progression of the severe form of the disease. In this review we will focus on the reversible oxidation of protein cysteines during the course of acute pancreatitis. We describe disulfide stress in an…
Protein-bound tyrosine oxidation, nitration and chlorination by-products assessed by ultraperformance liquid chromatography coupled to tandem mass sp…
2015
Abstract Background Free radicals cause alterations in cellular protein structure and function. Oxidized, nitrated, and chlorinated modifications of aromatic amino acids including phenylalanine and tyrosine are reliable biomarkers of oxidative stress and inflammation in clinical conditions. Objective To develop, validate and apply a rapid method for the quantification of known hallmarks of tyrosine oxidation, nitration and chlorination in plasma and tissue proteins providing a snapshot of the oxidative stress and inflammatory status of the organism and of target organs respectively. Material and Methods The extraction and clean up procedure entailed protein precipitation, followed by protei…
Haemoglobin in ascitic fluid increases lipid peroxidation in acute pancreatitis
2012
Oxidative and nitrosative stress in acute pancreatitis. Modulation by pentoxifylline and oxypurinol
2011
Item does not contain fulltext Reactive oxygen species are considered mediators of the inflammatory response and tissue damage in acute pancreatitis. We previously found that the combined treatment with oxypurinol - as inhibitor of xanthine oxidase- and pentoxifylline - as inhibitor of TNF-alpha production-restrained local and systemic inflammatory response and decreased mortality in experimental acute pancreatitis. Our aims were (1) to determine the time-course of glutathione depletion and oxidation in necrotizing pancreatitis in rats and its modulation by oxypurinol and pentoxifylline; (2) to determine whether TNF-alpha is responsible for glutathione depletion in acute pancreatitis; and (…
Co-administration of pentoxifylline and thiopental causes death by acute pulmonary oedema in rats
2006
Background and purpose: Pentoxifylline exhibits rheological properties that improve microvascular flow and it is widely used in vascular perfusion disorders. It also exhibits marked anti-inflammatory properties by inhibiting tumour necrosis factor a production. Thiopental is one of the most widely used drugs for rapid induction of anaesthesia. During experimental studies on the treatment of acute pancreatitis, we observed that when pentoxifylline was administered after anaesthesia with thiopental, most of the rats exhibited dyspnea, signs of pulmonary oedema and died. The aim of the work described here was to investigate the cause of the unexpected toxic effect of the combined treatment wit…
Role of Redox Signaling, Protein Phosphatases and Histone Acetylation in the Inflammatory Cascade in Acute Pancreatitis: Therapeutic Implications
2010
Acute pancreatitis starts as a local inflammation of the pancreatic tissue but often leads to the systemic inflammatory response syndrome and death by multiple organ failure. Pro-inflammatory cytokines, particularly TNF-alpha and Il-1beta, play a pivotal role together with oxidative stress and glutathione depletion in the inflammatory response in this disease. Most inflammatory mediators act through mitogen activated protein kinases and nuclear factor kB. Nevertheless, elucidation of the precise mechanisms involved in activation and attenuation phases of the inflammatory cascade is still underway. Redox signaling mediated by inactivation of protein phosphatases and histone acetylation trigg…
Elevated protein carbonyl and HIF-1α levels in eyes with proliferative diabetic retinopathy.
2013
Purpose: To evaluate the role of protein carbonyls and hypoxia inducible factor-1a (HIF-1a) in diabetic eyes with proliferative diabetic retinopathy (PDR). Methods: Prospective consecutive controlled observational study was performed. Vitreous samples were collected at the start of the 3-ppp vitrectomy. Protein carbonylation analysis was performed by Western blotting with antibody against 2,4-Dinitrophenol (anti-DNP), following derivatization of protein carbonyls with 2,4 Dinitrophenylhydrazine (DNHP). Protein carbonylation was quantified by scanning densitometry analysis and relativized to the total amount of protein into the ponceau staining of membranes. Vitreous HIF-1 a was determined w…
Glutamate cysteine ligase up-regulation fails in necrotizing pancreatitis
2007
Glutathione depletion is a key factor in the development of acute pancreatitis. Our aim was to study the regulation of glutamate cysteine ligase, the rate-limiting enzyme in glutathione synthesis, in edematous or necrotizing pancreatitis in rats. Glutathione levels were kept low in necrotizing pancreatitis for several hours, with no increase in protein or mRNA levels of glutamate cysteine ligase subunits, despite binding of RNA polymerase II to their promoters and coding regions. The survival signal pathway mediated by ERK and c-MYC was activated, and c-MYC was recruited to the promoters. The failure in gene up-regulation seems to be due to a marked increase in cytosolic ribonuclease activi…
Protein phosphatases and chromatin modifying complexes in the inflammatory cascade in acute pancreatitis
2010
Acute pancreatitis is an inflammation of the pancreas that may lead to systemic inflammatory response syndrome and death due to multiple organ failure. Acinar cells, together with leukocytes, trigger the inflammatory cascade in response to local damage of the pancreas. Amplification of the inflammatory cascade requires up-regulation of pro-inflammatory cytokines and this process is mediated not only by nuclear factor κB but also by chromatin modifying complexes and chromatin remodeling. Among the different families of histone acetyltransferases, the p300/CBP family seems to be particularly associated with the inflammatory process. cAMP activates gene expression via the cAMP-responsive eleme…
Prolonging in utero-like oxygenation after birth diminishes oxidative stress in the lung and brain of mice pups☆
2013
Background Fetal-to-neonatal transition is associated with oxidative stress. In preterm infants, immaturity of the antioxidant system favours supplemental oxygen-derived morbidity and mortality. Objectives To assess if prolonging in utero-like oxygenation during the fetal-to-neonatal transition limits oxidative stress in the lung and brain, improving postnatal adaptation of mice pups. Material and methods Inspiratory oxygen fraction (FiO2) in pregnant mice was reduced from 21% (room air) to 14% (hypoxia) 8–12 h prior to delivery and reset to 21% 6–8 h after birth. The control group was kept at 21% during the procedure. Reduced (GSH) and oxidized (GSSG) glutathione and its precursors [γ-glut…
7,8-hydroxy-2′-deoxyguanosine/2′-deoxiguanosine ratio determined in hydrolysates of brain DNA by ultrachromatrography coupled to tandem mass spectrom…
2017
7,8-hydroxy-2'-deoxyguanosine (8-OHdG) is an abundant DNA lesion formed by oxidation of the nucleoside 2'-deoxyguanosine (2-dG) and one of the most studied and accepted oxidative stress biomarkers. 8-OHdG has a strong carcinogenic potential, and prolonged oxidative stress heightens pathological conditions and especially cancer risk. Our aim was to develop, validate and apply a reliable method to assess DNA oxidation in genomic cellular DNA of sensible target organs such as brain. A procedure to isolate and digest the DNA of brain tissue properly for further detection of 8-OHdG and 2-dG by Ultra Performance Liquid Chromatography tandem Mass Spectrometry (UPLC-MS/MS) was optimized. The UPLC-M…
Cross-talk between oxidative stress and pro-inflammatory cytokines in acute pancreatitis: a key role for protein phosphatases.
2009
Acute pancreatitis is an acute inflammatory process localized in the pancreatic gland that frequently involves peripancreatic tissues. It is still under investigation why an episode of acute pancreatitis remains mild affecting only the pancreas or progresses to a severe form leading to multiple organ failure and death. Proinflammatory cytokines and oxidative stress play a pivotal role in the early pathophysiological events of the disease. Cytokines such as interleukin 1beta and tumor necrosis factor alpha initiate and propagate almost all consequences of the systemic inflammatory response syndrome. On the other hand, depletion of pancreatic glutathione is an early hallmark of acute pancreat…
Infrared biospectroscopy for a fast qualitative evaluation of sample preparation in metabolomics.
2014
Liquid chromatography-mass spectrometry (LC-MS) has been increasingly used in biomedicine to study the dynamic metabolomic responses of biological systems under different physiological or pathological conditions. To obtain an integrated snapshot of the system, metabolomic methods in biomedicine typically analyze biofluids (e.g. plasma) that require clean-up before being injected into LC-MS systems. However, high resolution LC-MS is costly in terms of resources required for sample and data analysis and care must be taken to prevent chemical (e.g. ion suppression) or statistical artifacts. Because of that, the effect of sample preparation on the metabolomic profile during metabolomic method d…
Redox signaling and histone acetylation in acute pancreatitis
2011
Histone acetylation via CBP/p300 coordinates the expression of proinflammatory cytokines in the activation phase of inflammation, particularly through mitogen-activated protein kinases (MAPKs), nuclear factor-κB (NF-κB), and signal transducers and activators of transcription (STAT) pathways. In contrast, histone deacetylases (HDACs) and protein phosphatases are mainly involved in the attenuation phase of inflammation. The role of reactive oxygen species (ROS) in the inflammatory cascade is much more important than expected. Mitochondrial ROS act as signal-transducing molecules that trigger proinflammatory cytokine production via inflammasome-independent and inflammasome-dependent pathways. …
Sex-dependent changes in the pulmonary vasoconstriction potential of newborn rats following short-term oxygen exposure
2012
Chronic exposure to supplemental oxygen (O(2)) induces lung damage and mortality in a sex-dependent manner. The effect of short-term hyperoxia on the newborn pulmonary vasculature is unknown but is, however, of clinical significance in the neonatal resuscitation context. We hypothesize that short-term hyperoxia has a sex-dependent effect on the pulmonary vasculature.Following 1-h 100% O(2) exposure, the pulmonary arteries and lung tissues of newborn rats were evaluated.Superoxide dismutase 3 (SOD3) expression in female pups' lungs was increased as compared with that in the lungs of male pups. As compared with air-treated pups, the response of male pups to thromboxane was increased by O(2), …
Assessment of oxidative damage to proteins and DNA in urine of newborn infants by a validated UPLC-MS/MS approach
2014
The assessment of oxidative stress is highly relevant in clinical Perinatology as it is associated to adverse outcomes in newborn infants. This study summarizes results from the validation of an Ultra Performance Liquid Chromatography-tandem Mass Spectrometry (UPLC-MS/MS) method for the simultaneous quantification of the urinary concentrations of a set of endogenous biomarkers, capable to provide a valid snapshot of the oxidative stress status applicable in human clinical trials, especially in the field of Perinatology. The set of analytes included are phenylalanine (Phe), para-tyrosine (p-Tyr), ortho-tyrosine (o-Tyr), meta-tyrosine (m-Tyr), 3-NO2-tyrosine (3NO(2)-Tyr), 3-Cl-tyrosine (3Cl-T…
Pentoxifylline Prevents Loss of PP2A Phosphatase Activity and Recruitment of Histone Acetyltransferases to Proinflammatory Genes in Acute Pancreatitis
2009
Mitogen-activated protein kinases (MAPKs) are considered major signal transducers early during the development of acute pancreatitis. Pentoxifylline is a phosphodiesterase inhibitor with marked anti-inflammatory properties through blockade of extracellular signal regulated kinase (ERK) phosphorylation and tumor necrosis factor alpha production. Our aim was to elucidate the mechanism of action of pentoxifylline as an anti-inflammatory agent in acute pancreatitis. Necrotizing pancreatitis induced by taurocholate in rats and taurocholate-treated AR42J acinar cells were studied. Phosphorylation of ERK and ERK kinase (MEK1/2), as well as PP2A, PP2B, and PP2C serine/threonine phosphatase activiti…
Disulfide stress as a novel type of oxidative stress in acute inflammation
2012
Antenatal Steroids and Antioxidant Enzyme Activity in Preterm Infants: Influence of Gender and Timing
2009
Antenatal steroids have improved the survival of preterm infants; however, the mechanism of action is not fully understood. We aimed to establish an association between antenatal steroids and antioxidant activity and postnatal oxidative stress. In a prospective cohort study, extremely preterm neonates receiving antenatal steroids (CORT) or not (NOCORT) were enrolled. An association between antenatal steroids and activities of antioxidant enzymes and glutathione cycle enzymes in cord blood was found. In addition, reduced oxidative stress (GSH/GSSG ratio, CORT vs. NOCORT, 35.68 + or - 12.20 vs. 28.38 + or - 9.92; p < 0.01) and, decreased oxidation of proteins (ortho-tyrosine/phenylalanine rat…
Disulfide stress: a novel type of oxidative stress in acute pancreatitis.
2013
Glutathione oxidation and protein glutathionylation are considered hallmarks of oxidative stress in cells because they reflect thiol redox status in proteins. Our aims were to analyze the redox status of thiols and to identify mixed disulfides and targets of redox signaling in pancreas in experimental acute pancreatitis as a model of acute inflammation associated with glutathione depletion. Glutathione depletion in pancreas in acute pancreatitis is not associated with any increase in oxidized glutathione levels or protein glutathionylation. Cystine and homocystine levels as well as protein cysteinylation and γ-glutamyl cysteinylation markedly rose in pancreas after induction of pancreatitis…
γ-Glutamylcysteine detoxifies reactive oxygen species by acting as glutathione peroxidase-1 cofactor
2012
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Metabolomic Analysis of the Effect of Postnatal Hypoxia on the Retina in a Newly Born Piglet Model
2013
The availability of reliable biomarkers of brain injury secondary to birth asphyxia could substantially improve clinical grading, therapeutic intervention strategies, and prognosis. In this study, changes in the metabolome of retinal tissue caused by profound hypoxia in an established neonatal piglet model were investigated using an ultra performance liquid chromatography - quadrupole time of flight mass spectrometry (UPLC-QTOFMS) untargeted metabolomic approach, which included Partial Least Squares - Discriminant Analysis (PLSDA) multivariate data analysis. The initial identification of a set of discriminant metabolites from UPLC-QTOFMS data was confirmed by target UPLC-MS/MS and allowed t…