Novel biomarkers in amniotic fluid for early assessment of intraamniotic infection

Cháfer-Pericás, Consuelo; Stefanović, Vedran; Sánchez-Illana, Ángel; Escobar, Javier; Cernada, María; Cubells, Elena; Núñez-Ramiro, Antonio; Andersson, Sture; Vento, Máximo; Kuligowski, Julia

doi:10.1016/j.freeradbiomed.2015.09.014

Cited by 20 publications

(14 citation statements)

References 28 publications

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“…Of note, we initiated treatment only after the animals had already experienced five full days of harmful neuroinflammation, known to cause maturation blockade of oligodendrocytes (Favrais et al, 2011;Schang et al, 2014). As prenatal exposure to inflammation (Baumbusch et al, 2016;Chafer-Pericas et al, 2015;Tronnes et al, 2014) and prenatal changes in the brain have been observed in infants who go on to be born preterm (Thomason et al, 2017) this efficacy with a delayed start provides significant clinical relevance to our study. Our results confirm the neurotherapeutic effects of targeting the H3R for white matter injury seen in a cuprizone model of multiple sclerosis (Wang et al, 2014) and a recently reported clinical trial in relapsing-remitting multiple sclerosis patients (Schwartzbach et al, 2017).…”

Section: Discussionmentioning

confidence: 98%

Myelination induction by a histamine H3 receptor antagonist in a mouse model of preterm white matter injury

Rangon

Schang

Steenwinckel

et al. 2018

Brain, Behavior, and Immunity

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Fifteen million babies are born preterm every year and a significant number suffer from permanent neurological injuries linked to white matter injury (WMI). A chief cause of preterm birth itself and predictor of the severity of WMI is exposure to maternal-fetal infection-inflammation such as chorioamnionitis. There are no neurotherapeutics for this WMI. To affect this healthcare need, the repurposing of drugs with efficacy in other white matter injury models is an attractive strategy. As such, we tested the efficacy of GSK247246, an H3R antagonist/inverse agonist, in a model of inflammation-mediated WMI of the preterm born infant recapitulating the main clinical hallmarks of human brain injury, which are oligodendrocyte maturation arrest, microglial reactivity, and hypomyelination. WMI is induced by mimicking the effects of maternal-fetal infection-inflammation and setting up neuroinflammation. We induce this process at the time in the mouse when brain development is equivalent to the human third trimester; postnatal day (P)1 through to P5 with i.p. interleukin-1β (IL-1β) injections. We initiated GSK247246 treatment (i.p at 7 mg/kg or 20 mg/kg) after neuroinflammation was well established (on P6) and it was administered twice daily through to P10. Outcomes were assessed at P10 and P30 with gene and protein analysis. A low dose of GSK247246 (7 mg/kg) lead to a recovery in protein expression of markers of myelin (density of Myelin Basic Protein, MBP & Proteolipid Proteins, PLP) and a reduction in macro- and microgliosis (density of ionising adaptor protein, IBA1 & glial fibrillary acid protein, GFAP). Our results confirm the neurotherapeutic efficacy of targeting the H3R for WMI seen in a cuprizone model of multiple sclerosis and a recently reported clinical trial in relapsing-remitting multiple sclerosis patients. Further work is needed to develop a slow release strategy for this agent and test its efficacy in large animal models of preterm infant WMI.

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Section: Discussionmentioning

confidence: 98%

Myelination induction by a histamine H3 receptor antagonist in a mouse model of preterm white matter injury

Rangon

Schang

Steenwinckel

et al. 2018

Brain, Behavior, and Immunity

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“…These results disagree with those reported by Temma et al [ 51 ], who showed increased oxidative stress in human placenta with HC. Similarly, a recent study by Cháfer-Pericás et al [ 52 ] demonstrated elevated oxidative stress in amniotic fluid in the presence of intra-amniotic infection. Additionally, Perrone et al [ 53 ] observed that HC was associated with higher oxidative stress levels in umbilical cord blood.…”

Section: Discussionmentioning

confidence: 74%

Histologic chorioamnionitis does not modulate the oxidative stress and antioxidant status in pregnancies complicated by spontaneous preterm delivery

Martín

Moço

Lima

et al. 2017

BMC Pregnancy Childbirth

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BackgroundInfection induced-inflammation and other risk factors for spontaneous preterm birth (PTB) and preterm premature rupture of membranes (pPROM) may cause a redox imbalance, increasing the release of free radicals and consuming antioxidant defenses. Oxidative stress, in turn, can initiate intracellular signaling cascades that increase the production of pro-inflammatory mediators.The objective of this study was to evaluate the oxidative damage to proteins and antioxidant capacity profiles in amniochorion membranes from preterm birth (PTB) and preterm premature rupture of membranes (pPROM) and to determine the role of histologic chorioamnionitis in this scenario.MethodsWe included 27 pregnant women with PTB, 27 pPROM and 30 at term. Protein oxidative damage was assayed by 3-nitrotyrosine (3-NT) and carbonyl levels, using enzyme-linked immunosorbent assay (ELISA) and modified dinitrophenylhydrazine assay (DNPH), respectively. Total antioxidant capacity (TAC) was measured by ELISA.ResultsProtein oxidative damage determined by carbonyl levels was lower in PTB group than pPROM and term groups (p < 0.001). PTB group presented higher TAC compared with pPROM and term groups (p = 0.002). Histologic chorioamnionitis did not change either protein oxidative damage or TAC regardless of gestational outcome.ConclusionThese results corroborates previous reports that pPROM and term birth exhibit similarities in oxidative stress- induced senescence and histologic chorioamnionitis does not modulate oxidative stress or antioxidant status.

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“…All biomarkers were quantified simultaneously, employing an LC-MS/MS system according to previously validated methods [12,16] with slight modifications. The Acquity-Xevo TQ-S system (Waters, Milford, MA, USA) was employed for the analysis, operating in positive electrospray mode (ESI + ).…”

Section: Methodsmentioning

confidence: 99%

Protein Oxidation Biomarkers and Myeloperoxidase Activation in Cerebrospinal Fluid in Childhood Bacterial Meningitis

Rugemalira

Roine

Kuligowski³

et al. 2019

Antioxidants

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The immunological response in bacterial meningitis (BM) causes the formation of reactive oxygen and nitrogen species (ROS, RNS) and activates myeloperoxidase (MPO), an inflammatory enzyme. Thus, structural oxidative and nitrosative damage to proteins and DNA occurs. We aimed to asses these events in the cerebrospinal fluid (CSF) of pediatric BM patients. Phenylalanine (Phe), para-tyrosine (p-Tyr), nucleoside 2′-deoxiguanosine (2dG), and biomarkers of ROS/RNS-induced protein and DNA oxidation: ortho-tyrosine (o-Tyr), 3-chlorotyrosine (3Cl-Tyr), 3-nitrotyrosine (3NO₂-Tyr) and 8-oxo-2′-deoxyguanosine (8OHdG), concentrations were measured by liquid chromatography coupled to tandem mass spectrometry in the initial CSF of 79 children with BM and 10 without BM. All biomarkers, normalized with their corresponding precursors, showed higher median concentrations (p < 0.0001) in BM compared with controls, except 8OHdG/2dG. The ratios o-Tyr/Phe, 3Cl-Tyr/p-Tyr and 3NO₂-Tyr/p-Tyr were 570, 20 and 4.5 times as high, respectively. A significantly higher 3Cl-Tyr/p-Tyr ratio was found in BM caused by Streptococcus pneumoniae, than by Haemophilus influenzae type b, or Neisseria meningitidis (p = 0.002 for both). In conclusion, biomarkers indicating oxidative damage to proteins distinguished BM patients from non-BM, most clearly the o-Tyr/Phe ratio. The high 3Cl-Tyr/p-Tyr ratio in pneumococcal meningitis suggests robust inflammation because 3Cl-Tyr is a marker of MPO activation and, indirectly, of inflammation.

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Novel biomarkers in amniotic fluid for early assessment of intraamniotic infection

Cited by 20 publications

References 28 publications

Myelination induction by a histamine H3 receptor antagonist in a mouse model of preterm white matter injury

Myelination induction by a histamine H3 receptor antagonist in a mouse model of preterm white matter injury

Histologic chorioamnionitis does not modulate the oxidative stress and antioxidant status in pregnancies complicated by spontaneous preterm delivery

Protein Oxidation Biomarkers and Myeloperoxidase Activation in Cerebrospinal Fluid in Childhood Bacterial Meningitis

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