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Nitric oxide inhalation inhibits inducible nitric oxide synthase but not nitrotyrosine formation and cell apoptosis in rat lungs with meconiuminduced injury

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Acta Pharmacologica Sinica 2005年第9期26卷 1123-1129页

作者： Mei-ping LU Li-zhong DU~2 Wei-zhong GU Xiang-xiang CHEN neonatal intensive care Unit,department of pediatrics,Children’s Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China department of pediatrics Neonatal Intensive Care Unit Children's Hospital Zhejiang University School of Medicine Hangzhou China

Aim:To investigate the effects of inhaled nitric oxide(NO)on pulmonaryinflammation,apoptosis,peroxidation and protein nitration in a rat model of acutelung injury(ALI)induced by ***:Twenty-four healthy maleSprague-Dawley rats were randomly devided into 3 groups(n=8):meconium-induced ALl with intratracheal instillation of 1 mL/kg saline(Mec/saline group),continuous inhalation of NO at 20 μL/L.(Mec/iNO),and the control group(control).Electromicroscopic examination was used to determine the extent of *** was used to detect DNA fragmentation in pulmonary apoptoticcells,expressed as the apoptosis index(AI).Western blotting was used to detectpulmonary inducible NO synthase(iNOS)***-PCR was used to detectinterleukin(IL)-1β mRNA *** count in bronchoalveolar lavage(BAL),myeloperoxidase(MPO)activity,as well as malondialdehyde(MDA)andnitrotyrosine formation,the markers of toxic NO-superoxide pathway in rat lungparenchyma specimens,were also ***:Expression of iNOS pro-tein and IL- 113 mRNA were increased significantly in the Mec/saline group(bothP<0.01)compared with the control *** cell count,MPO activity,lunginjury score,pulmonary AI,MDA level and nitrotyrosine formation were alsoincreased significantly(all P<0.01).The meconium-induced iNOS protein andIL-1β mRNA expression were inhibited significantly by NO inhalation when com-pared with the Mec/saline group(both P<0.01 ).BAL cell count,MPO activity andlung injury score were also decreased significantly(P<0.01 or P<0,05).However,there were no statistical differences in MDA level,nitrotyrosine formation or pul-monary AI between the Mec/saline and Mec/iNO *** revealed a significant degree of epithelial apoptosis in both the Mec/saline and Mec/iNO ***:Early continuous inhalation of NO20 μL/L may protect the lungs from inflammatory injury,but does not decreaseepithelial apoptosis or lung nitrotyrosine formati

关键词： inhaled nitric oxide meconium acute lung injury nitrotyrosine apoptosis

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Magnesium sulfate and fetal neuroprotection: overview of clinical evidence

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Neural Regeneration Research 2018年第12期13卷 2044-2049页

作者： Clément Chollat Stéphane Marret Institut National de la Santé et de la Recherche Médicale U1245 Genetics and Pathophysiology of Neurodevelopmental Disorders Team 4Neovasc Institute of Research and Innovation in Biomedicine Rouen School of Medicine Normandy University department of neonatal intensive care Port Royal University Hospital department of neonatal pediatrics and intensive care and neuropediatrics Charles-Nicolle University Hospital

Antenatal administration of magnesium sulfate is an important part of the neuroprotective strategy for preterm infants. Strong evidence from five randomized controlled trials and five meta-analyses has demonstrated that magnesium sulfate, when administered before preterm delivery, significantly reduces the risk of cerebral palsy at two years. Through secondary analyses of randomized controlled trials and other original clinical studies, this state-of-the-art review highlights the absence of serious adverse effects in both pregnant women and neonates, as well as the impact of maternal body mass index and preeclamptic status on the maternal and neonatal magnesium levels, which could influence the magnitude of the neuroprotective effect. Although antenatal magnesium sulfate is a cost-effective strategy, some practice surveys have demonstrated that the use of magnesium sulfate is not sufficient and that its use is heterogeneous, differing among different maternity wards. Since 2010, an increasing number of obstetrical societies have recommended its use to improve the neurological outcomes of preterm infants, especially the International Federation of Gynecology and Obstetrics and World Health Organization in 2015, and France in 2017. Considering the neuroprotective impact of magnesium sulfate when administered before delivery, postnatal administration should be considered, and its effects should be assessed using randomized controlled trials.

关键词： magnesium sulfate preterm birth neuroprotection cerebral palsy neurodevelopment international recommendations clinical studies meta-analysis preeclampsia cost-effectiveness

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Urinary tract infections in neonates with jaundice in their first two weeks of life

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World Journal of pediatrics 2014年第2期10卷 164-167页

作者： Mehmet Mutlu Yasemin Cayır Yakup Aslan department of Neonatology Erzurum Regional Training and Research HospitalNeonatal Intensive Care UnitErzurumTurkey department of Family Physician Erzurum Regional Training and Research HospitalNeonatal Intensive Care UnitErzurumTurkey department of Neonatology Karadeniz Technical UniversityNeonatal Intensive Care UnitTrabzonTurkey

Background:Hyperbilirubinemia is a frequently seen condition in *** study was undertaken to determine the role of urinary tract infections(UTIs)in the etiology of indirect hyperbilirubinemia in neonates with jaundice in their fi rst two weeks of ***:The study was conducted *** subjects were neonates aged 4-14 days with hyperbilirubinemia which could not be detected by routine tests and was suffi ciently severe to necessitate ***:The study was performed in 104 neonates,of whom 18%(n=19)had *** most frequently identified micro-organism was Escherichia coli(43%).Phototherapy duration and rebound bilirubin level were higher in neonates with UTI(P<0.05).Conclusion:UTI should be investigated in neonates with hyperbilirubinemia of unknown etiology in the fi rst two weeks of life.

关键词： hyperbilirubinemia neonate urinary tract infection

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Gastroesophageal reflux and congenital gastrointestinal malformations

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World Journal of Gastroenterology 2015年第28期21卷 8508-8515页

作者： Lucia Marseglia Sara Manti Gabriella D'Angelo Eloisa Gitto Carmelo Salpietro Antonio Centorrino Gianfranco Scalfari Giuseppe Santoro Pietro Impellizzeri Carmelo Romeo neonatal intensive care Unit Department of Pediatrics University of Messina Unit of Paediatric Genetics and Immunology Department of Paediatrics University of Messina Unit of Pediatric Surgery Department of Pediatrics University of Messina department of Biomedical Sciences and Morpho-Functional Images University of Messina

Although the outcome of newborns with surgical congenital diseases(e.g.,diaphragmatic hernia;esophageal atresia;omphalocele;gastroschisis) has improved rapidly with recent advances in perinatal intensive care and surgery,infant survivors often require intensive treatment after birth,have prolonged hospitalizations,and,after discharge,may have longterm sequelae including gastro-intestinal comorbidities,above all,gastroesophageal reflux(GER).This condition involves the involuntary retrograde passage of gastric contents into the esophagus,with or without regurgitation or *** is a well-recognized condition,typical of infants,with an incidence of 85%,which usually resolves after physiological maturation of the lower esophageal sphincter and lengthening of the intra-abdominal esophagus,in the first few months after *** the exact cause of abnormal esophageal function in congenital defects is not clearly understood,it has been hypothesized that common(increased intra-abdominal pressure after closure of the abdominal defect) and/or specific(e.g.,motility disturbance of the upper gastrointestinal tract,damage of esophageal peristaltic pump) pathological mechanisms may play a role in the etiology of GER in patients with birth *** of knowledge could positively impact the long-term prognosis of patients with surgical congenital *** present manuscript provides a literature review focused on pathological and clinical characteristics of GER in patients who have undergone surgical treatment for congenital abdominal malformations.

关键词： Gastroesophageal reflux Congenital diaphragmatichernia Esophageal atresia Omphalocele Gastroschisis

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Sex differences in the risk of retinopathy of prematurity:a systematic review,frequentist and Bayesian meta‑analysis,and meta‑regression

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World Journal of pediatrics 2024年第4期20卷 340-352页

作者： Tamara M.Hundscheid Silvia Gulden Mohamad F.Almutairi František Bartoš Giacomo Cavallaro Eduardo Villamor Division of Neonatology Department of PediatricsMosaKids Children’s HospitalMaastricht University Medical Center(MUMC+)School for Oncology and Reproduction(GROW)Maastricht UniversityP.Debyelaan 25.P.O.Box 58006202 AZ MaastrichtThe Netherlands neonatal intensive care Unit Sant’Anna HospitalComoItaly department of Psychology University of Amsterdam1001 NK AmsterdamThe Netherlands neonatal intensive care Unit Fondazione IRCCS Ca’Granda Ospedale Maggiore PoliclinicoMilanItaly

Background Retinopathy of prematurity(ROP)is generally considered to be more frequent in males than in ***,it is not known whether sex differences in ROP affect all degrees of the condition,are global and have changed as neonatology has *** aimed to conduct a systematic review and meta-analysis of studies addressing sex differences in the risk of developing *** PubMed/MEDLINE and Embase databases were *** frequentist,random-effects risk ratio(RR)and 95%confidence interval(CI)were *** model averaged(BMA)meta-analysis was used to calculate the Bayes factors(BFs).The BF10 is the ratio of the probability of the data under the alternative hypothesis(H1)over the probability of the data under the null hypothesis(H0).Results We included 205 studies(867,252 infants).Frequentist meta-analysis showed a positive association between male sex and severe ROP(113 studies,RR=1.14,95%CI=1.07–1.22)but no association with any ROP(144 studies,RR=1.00,95%CI=0.96–1.03).BMA showed extreme evidence in favor of H1 for severe ROP(BF10=71,174)and strong evidence in favor of H0 for any ROP(BF10=0.05).The association between male sex and severe ROP remained stable over time and was present only in cohorts from countries with a high or high-middle sociodemographic *** Our study confirms the presence of a male disadvantage in severe ROP but not in less severe forms of the *** are variations in the sex differences in ROP,depending on geographical location and sociodemographic level of the countries.

关键词： Oxidative stress Retinopathy of prematurity Sex characteristics

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Aluminum exposure and toxicity in neonates:a practical guide to halt aluminum overload in the prenatal and perinatal periods

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World Journal of pediatrics 2014年第2期10卷 101-107页

作者： Daniela Fanni Rossano Ambu Clara Gerosa Sonia Nemolato Nicoletta Iacovidou Peter Van Eyken Vassilios Fanos Marco Zaffanello Gavino Faa department of Pathology University Hospital San Giovanni di DioAOU Cagliari and University of CagliariItaly National and Kapodistrian University of Athens Medical SchoolAthensGreece department of Pathology K.U.LeuvenLeuvenBelgium neonatal intensive care Unit Puericulture Institute and Neonatal SectionAOU Cagliari and University of CagliariItaly department of pediatrics University of VeronaItaly

Background:During the last years,human newborns have been overexposed to biologically reactive aluminum,with possible relevant consequences on their future health and on their susceptibility to a variety of ***,newborns and particularly preterm neonates are at an increased risk of aluminum toxicity because of their relative *** sources:Based on recent original publications and classical data of the literatures,we reviewed the aluminum content in mother's food during the intrauterine life as well as in breast milk and infant formula during *** also determined the possible role of aluminum in parenteral nutrition solutions,in adjuvants of vaccines and in pharmaceutical products.A special focus is placed on the relationship between aluminum overexposure and the insurgence of bone ***:Practical points of management and prevention are *** sources that infants may receive during the fi rst 6 months of life are *** the context of prevention of possible adverse effects of aluminum overload in fetal tissues during development,simple suggestions to pregnant women are ***,practical points of management and prevention are ***:Pediatricians and neonatologists must be more concerned about aluminum content in all products our newborns are exposed to,starting from monitoring aluminum concentrations in milk-and soybased formulas in which,on the basis of recent studies,there is still too much aluminum.

关键词： aluminum fetus newborn toxicity

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Early Intratracheal Administration of Corticosteroid and Pulmonary Surfactant for Preventing Bronchopulmonary Dysplasia in Preterm Infants with neonatal Respiratory Distress Syndrome: A Meta-analysis

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Current Medical Science 2019年第3期39卷 493-499页

作者： Yan-yan ZHONG Jin-chun LI Ya-ling LIU Xiao-bo ZHAO Musa MALE Dong-kui SONG Yan BAI department of pediatrics Huazhong University of Science and Technology Hospital Wuhan 430074China neonatal intensive care Unit Hubei Maternity and Children's Hospital Wuhan 430070China department of pediatrics Union Hospital Tongji Medical College Huazhong University of Science and TechnologyWuhan 430022 China department of Urology Tongji Hospital Tongji Medical College Huazhong University of Science and TechnologyWuhan 430030 China

There is uncertain result with regard to the use of inhalation or instillation steroids to prevent bronchopulmonary dysplasia in preterm infants. This meta-analysis was designed to evaluate the efficacy and safety of early airway administration (within 2 days after birth) of corticosteroids and pulmonary surfactant (PS) for preventing bronchopulmonary dysplasia (BPD) in premature infants with neonatal respiratory distress syndrome (NRDS). The related studies were retrieved in PubMed, EMBASE, the Cochrane Library, Clinical Trial, CNKI, Wanfang and VIP Database from inception to August 2018. Two reviewers independently screened the studies to ensure that all patients with diagnosis of NRDS were enrolled to studies within 1 day after birth, assessed the quality of included studies by GRADEpro system and extracted the data for review. The meta-analysis was performed by RevMan 5.2 software. A subgroup analysis about inhaled corticosteroid (ICS) delivery method was made between ICS inhalation subgroup [inhalation of ICS by nebulizer or metered dose inhaler (MDI)] and ICS intratracheal instillation subgroup (PS used as a vehicle). Eight randomized controlled trials were enrolled in the meta-analysis, 5 trials of which stated the randomized method, grouping and blinded method, and the follow-up procedures were reported. GRADEpro system showed high quality of 4 trials (5 articles), and the rest 4 trials had moderate quality. Meta-analysis showed that the incidence of BPD was decreased in ICS group, the relative risk (RR) was 0.56 (95% CI: 0.42-0.76), and similar trends were found in ICS inhalation subgroup and ICS intratracheal instillation subgroup, with the corresponding RR being 0.58 (95% CI: 0.41-0.82) and 0.47 (95% CI: 0.24-0.95) respectively. ICS could also significantly reduce the mortality risk as compared with placebo control group (RR: 0.67;95% CI: 0.45-0.99), with RR of ICS inhalation subgroup and ICS intratracheal instillation subgroup being 0.81 (95% CI: 0.34-1.

关键词： corticosteroid pulmonary surfactant preterm infants bronchopulmonary dysplasia neonatal respiratory distress syndrome meta-analysis

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Serial physical examinations, a simple and reliable tool for managing neonates at risk for early-onset sepsis

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World Journal of Clinical pediatrics 2016年第4期5卷 358-364页

作者： Alberto Berardi Anna Maria Buffagni Cecilia Rossi Eleonora Vaccina Chiara Cattelani Lucia Gambini Federica Baccilieri Francesca Varioli Fabrizio Ferrari neonatal intensive care Unit Department of Mother and Child Policlinic University Hospital neonatal intensive care Unit Department of Obstetric and Pediatric Arcispedale Santa Maria Nuova

AIM To investigate whether serial physical examinations(SPEs) are a safe tool for managing neonates at risk for early-onset sepsis(EOS). METHODS This is a retrospective cohort study of neonates(≥ 34 wks' gestation) delivered in three high-volume level Ⅲbirthing centres in Emilia-Romagna(Italy) during a 4-mo period(from September 1 to December 31, 2015). Neonates at risk for EOS were managed according to the SPEs strategy, these were carried out in turn by bedside nursing staff and physicians. A standardized form detailing general wellbeing, skin colour and vital signs was filled in and signed at standard intervals(at age 3, 6, 12, 18, 36 and 48 h) in neonates at risk for EOS. Three independent reviewers reviewed all charts of neonates and abstracted data(gestational age, mode of delivery, group B streptococcus status, risk factors for EOS, duration of intrapartum antibiotic prophylaxis, postpartum evaluations, therapies and outcome). Rates of sepsis workups, empirical antibiotics and outcome of neonates at-risk(or not) for EOS were *** There were 2092 live births and 1 culture-proven EOS(Haemophilus i)(incidence rates of 0.48/1000 live births). Most newborns with signs of illness(51 out of 101, that is 50.5%), and most of those who received postpartum antibiotics(17 out of 29, that is 58.6%) were not at risk for EOS. Compared to neonates at risk, neonates not at risk for EOS were less likely to have signs of illness(51 out of 1442 vs 40 out of 650, P = 0.009) or have a sepsis workup(25 out of 1442 vs 28 out of 650, P < 0.001). However, they were not less likely to receive empirical antibiotics(17 out of 1442 vs 12 out of 650, P = 0.3). Thirty-two neonates were exposed to intrapartum fever or chorioamnionitis: 62.5%(n = 20) had a sepsis workup and 21.9%(n = 7) were given empirical antibiotics. Among 216 neonates managed through the SPEs strategy, only 5.6%(n = 12) had subsequently a sepsis workup and only 1.9%(n = 4) were given empirical antibiotics. Al

关键词： Sepsis Group B streptococcus Intrapartum antibiotic prophylaxis Newborn Prevention

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Hedgehog signaling pathway gene variant influences bronchopulmonary dysplasia in extremely low birth weight infants

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World Journal of pediatrics 2021年第3期17卷 298-304页

作者： Shaili Amatya Sharina Rajbhandari Sandeep Pradhan Van Trinh Umesh Paudel Lance A.Parton Newborn Medicine Division The Regional Neonatal Intensive Care UnitMaria Fareri Children's Hospital At Westchester Medical CenterValhallaNYUSA department of pediatrics New York Medical CollegeValhallaNYUSA department of pediatrics Penn State Children’s HospitalHersheyPAUSA Novant Health Presbyterian Medical Center CharlotteNCUSA department of Public Health Penn State UniversityHersheyPAUSA department of pediatrics Harlem Hospital-Columbia University Irving Medical CenterNew YorkNYUSA

Background Genome wide association study identified hedgehog interacting protein gene(HHIP)variants with chronic obstructive pulmonary disease and *** of HHIP,a key regulator of the hedgehog signaling pathway,leads to impaired lung morphogenesis and lethality in animal models,through unimpeded sonic hedgehog expression blocking mesenchymal-expressed fibroblast growth factor 10(FGF10).Since bronchopulmonary dysplasia(BPD)is also associated with altered lung development and worsens with stimuli including mechanical ventilation,reactive oxygen species,and inflammation,HHIP and FGF10 may be candidate *** This was an observational,cohort study including extremely low birth weight infants that who developed BPD and those who did *** was isolated from buccal swabs and subjected to allelic discrimination,using specific HHIP and FGF10 *** levels were measured in tracheal ***'s t test,Chi-square,Z test and logistic regression were *** Demographic characteristics did not differ except that birth weight(715±153 vs.835±132 g)and gestational age(25 vs.26 weeks)were less in babies with *** variant rs 13147758(GG genotype)was found to be independently protective for BPD(odds ratio 0.35,95%confidence interval 0.15-0.82,P=-0.02).Early airway HHIP protein levels were increased in infants with BPD compared to those without[median(interquartile range)130.6(55.6-297.0)and 41.2(22.1-145.6)pg/mL,respectively;P=0.05].The FGF10 single nucleotide polymorphisms were not associated with *** HHIP,as a regulator of lung bud formation,affects BPD susceptibility,and may be valuable in understanding the specific mechanisms for this disease as well as for identifying therapeutic targets in the era of personalized medicine.

关键词： Gene Infants Lung Preterm Single nucleotide polymorphism

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Natural heme oxygenase-1 inducers in hepatobiliary function

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World Journal of Gastroenterology 2008年第40期14卷 6122-6132页

作者： Giovanni Li Volti David Sacerdoti Claudia Di Giacomo Maria Luisa Barcellona Antonio Scacco Paolo Murabito Antonio Biondi Francesco Basile Diego Gazzolo Raul Abella Alessandro Frigiola Fabio Galvano department of Biological Chemistry Medical Chemistry and Molecular BiologyUniversity of Catania department of Clinical and Experimental Medicine University of Padova department of Surgery section of AnesthesiologyUniversity of Catania department of Surgery Section of General and Oncological SurgeryUniversity of Catania neonatal intensive care Unit "Cesare Arrigo" Children Hospital department of pediatrics G.Gaslini Children's University Hospital Perinatal Research Laboratory IRCSS San Donato Milanese

Many physiological effects of natural antioxidants, their extracts or their major active components, have been reported in recent decades. Most of these compounds are characterized by a phenolic structure, similar to that of o-tocopherol, and present antioxidant properties that have been demonstrated both in vitro and in vivo. Polyphenors may increase the capacity of endogenous antioxidant defences and modulate the cellular redox state. Changes in the cellular redox state may have wide-ranging consequences for cellular growth and differentiation. The majority of in vitro and in vivo studies conducted so far have attributed the protective effect of bioactive polyphenols to their chemical reactivity toward free radicals and their capacity to prevent the oxidation of important intracellular components. However, in recent years a possible novel aspect inthe mode of action of these compounds has been suggested; that is, the ultimate stimulation of the heme oxygenase-1 （HO-1） pathway is likely to account for the established and powerful antioxidant/anti-inflammatory properties of these polyphenols. The products of the HO-catalyzed reaction, particularly carbon mon- oxide （CO） and biliverdin/bilirubin have been shown to exert protective effects in several organs against oxidative and other noxious stimuli. In this context, it is interesting to note that induction of HO-1 expression by means of natural compounds contributes to protection against liver damage in various experimental models. The focus of this review is on the significance of targeted induction of HO-1 as a potential therapeutic strategy to protect the liver against various stressors in several pathological conditions.

关键词： Heme oxygenase Hepatobiliary function Natural inducers Carbon monoxide Oxidative stress

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