A5043220616- Neonatal Respiratory Health Research
- Pulmonary Hypertension Research and Treatments
- Congenital Diaphragmatic Hernia Studies
- Neuroscience of respiration and sleep
- Respiratory Support and Mechanisms
- Nitric Oxide and Endothelin Effects
- Congenital Heart Disease Studies
- Birth, Development, and Health
- Pregnancy and preeclampsia studies
- Neonatal Health and Biochemistry
- Mitochondrial Function and Pathology
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Cardiovascular Issues in Pregnancy
- Cancer, Hypoxia, and Metabolism
- Mechanical Circulatory Support Devices
- Cancer-related molecular mechanisms research
- ATP Synthase and ATPases Research
- Neonatal and fetal brain pathology
- Metabolism, Diabetes, and Cancer
- Heat shock proteins research
- Respiratory viral infections research
- MicroRNA in disease regulation
- Adenosine and Purinergic Signaling
- Redox biology and oxidative stress
- Pregnancy and Medication Impact
Medical College of Wisconsin
2016-2025
Children's Hospital of Wisconsin
2012-2023
Pediatrics and Genetics
2011-2023
Cardiovascular Research Center
2011-2022
Children's Research Hospital
2015
Milwaukee VA Medical Center
2008
Hutzel Women's Hospital
1991-2001
Wayne State University
1990-2001
Children's Hospital of Michigan
1991-2000
Boston Children's Hospital
1999
Inhaled nitric oxide is a controversial treatment for premature infants with severe respiratory failure. We conducted multicenter, randomized, blinded, controlled trial to determine whether inhaled reduced the rate of death or bronchopulmonary dysplasia in such infants.We randomly assigned 420 neonates, born at less than 34 weeks gestation, birth weight 401 1500 g, and failure more four hours after surfactant receive placebo (simulated flow) (5 10 ppm). Infants response (an increase partial...
Objective. The objective of this study was to detect fetal exposure nonsteroidal antiinflammatory drugs (NSAIDs) by meconium analysis and determine the relationship between NSAIDs development persistent pulmonary hypertension newborn (PPHN). Methods. In a case-control inborn outborn nurseries large urban medical center, collected from 101 infants (40 with diagnosis PPHN based on clinical or echocardiographic criteria 61 randomly selected, healthy, term [control]) analyzed for (ibuprofen,...
Objective. Inhaled nitric oxide (iNO) reduces the use of extracorporeal membrane oxygenation (ECMO)/incidence death in term and near-term neonates with severe hypoxic respiratory failure. We conducted a randomized, double masked, multicenter trial to determine whether administration iNO earlier failure results additional reduction incidence these outcomes. Methods. Neonates who were born at ≥34 weeks’ gestation enrolled when they required assisted ventilation had an index (OI) ≥15 <25...
Angiogenesis plays critical roles in the recovery phase of ischemic heart disease and peripheral vascular disease. An increase autophagy is protective under hypoxic chronic conditions. In present study we determined role angiogenesis. 3-Methyladenine (3-MA) small interfering RNA (siRNA) against ATG5 were used to inhibit induced by nutrient deprivation cultured bovine aortic endothelial cells (BAECs). Assays BAECs tube formation cell migration revealed that inhibition 3-MA or siRNA reduced...
Persistent pulmonary hypertension of newborn (PPHN) is associated with decreased NO release and impaired vasodilation. We investigated the hypothesis that increased superoxide (O(2)(*-)) by an uncoupled endothelial nitric oxide synthase (eNOS) contributes to vasodilation in PPHN. response isolated arteries NOS agonist ATP donor S-nitroso-N-acetylpenicillamine (SNAP) fetal lambs PPHN induced prenatal ligation ductus arteriosus sham-ligated controls presence or absence antagonist...
Rodent pups exposed to hyperoxia develop lung changes similar bronchopulmonary dysplasia (BPD) in extremely premature infants. Oxidative stress from can injure developing lungs through endoplasmic reticulum (ER) stress. Early caffeine treatment decreases the rate of BPD, but mechanisms remain unclear. We hypothesized that attenuates hyperoxia-induced injury its chemical chaperone property. Sprague-Dawley rat were raised either 90 (hyperoxia) or 21% (normoxia) oxygen postnatal day 1 (P1) 10...
Autophagy is a process for cells to degrade proteins or entire organelles maintain balance in the synthesis, degradation, and subsequent recycling of cellular products. Increased reactive oxygen species formation known induce autophagy. We previously reported that increased NADPH oxidase (NOX) activity pulmonary artery endothelial (PAEC) from fetal lambs with persistent hypertension (PPHN) contributes impaired angiogenesis PPHN-PAEC compared normal PAEC. hypothesized NOX associated...
Bronchopulmonary dysplasia (BPD) occurs in approximately 40% of infants born at younger than 30 weeks' gestation and is associated with adverse pulmonary neurodevelopmental outcomes.To test whether administration inhaled nitric oxide to preterm requiring positive pressure respiratory support on postnatal days 5 14 improves the rate survival without BPD.This intent-to-treat study was a randomized clinical trial performed 33 US Canadian neonatal intensive care units. Participants included 451...
A rapid increase in the synthesis and release of nitric oxide (NO) facilitates pulmonary vasodilation that occurs during birth-related transition. Alteration this transition persistent hypertension newborn (PPHN) is associated with impaired function endothelial synthase (eNOS) an oxidative stress. We investigated hypothesis a decrease expression activity mitochondrial localized manganese superoxide dismutase (MnSOD) artery cells (PAEC) increases stress impairs eNOS PPHN. isolated PAEC...
Impaired vasodilation in persistent pulmonary hypertension of the newborn (PPHN) is characterized by mitochondrial dysfunction. We investigated hypothesis that a decreased endothelial nitric oxide synthase level leads to impaired biogenesis and function lamb model PPHN induced prenatal ductus arteriosus constriction. ventilated lambs with 100% O2 alone or inhaled (iNO). treated artery cells (PAECs) from normal detaNONOate, an NO donor. observed (mt) DNA copy number, electron transport chain...
The import of superoxide dismutase-2 (SOD2) into mitochondria is vital for the survival eukaryotic cells. SOD2 encoded within nuclear genome and translocated activation after translation in cytosol. molecular chaperone Hsp70 modulates activity by promoting mitochondria. In turn, controlled co-chaperones, particularly CHIP, which directs Hsp70-bound proteins degradation proteasomes. We investigated mechanisms controlling to signal maintain mitochondrial redox balance. demonstrate that Akt1...
Persistent pulmonary hypertension of newborn (PPHN) is associated with decreased nitric oxide (NO) release and impaired vasodilation. We investigated the hypothesis that association heat shock protein 90 (HSP90) endothelial NO synthase (eNOS) impairs vasodilation in PPHN. The responses to NOS agonist ATP were fetal lambs PPHN induced by prenatal ligation ductus arteriosus, sham controls. caused dose-dependent control resistance arteries, this response was attenuated vessels. arteries N G...
Persistent pulmonary hypertension of newborn (PPHN) is associated with impaired vasodilation at birth. Previous studies demonstrated that a decrease in angiogenesis contributes to this failure postnatal adaptation. We investigated the hypothesis oxidative stress from NADPH oxidase (Nox) PPHN. PPHN was induced fetal lambs by ductus arteriosus ligation 85% term gestation. Pulmonary artery endothelial cells (PAEC) (HTFL-PAEC) or control (NFL-PAEC) were compared for their angiogenic activities...
Pulmonary artery endothelial cells (PAEC) isolated from fetal lambs with in utero pulmonary hypertension (IPH) have phenotypical changes that lead to increased reactive oxygen species (ROS) formation and impaired angiogenesis. AMP-activated protein kinase (AMPK) is known be activated by ROS, which expected help angiogenesis IPH-PAEC. The objectives of this study were investigate AMPK responses IPH its role We observed that, compared control PAEC, IPH-PAEC decreased phosphorylation AMPKα...
Superoxide dismutase 2 (SOD-2) is synthesized in the cytosol and imported into mitochondrial matrix, where it activated functions as primary antioxidant for cellular respiration. The specific mechanisms that target SOD-2 to mitochondria remain unclear. We hypothesize inducible heat shock protein 70 (iHSP70) targets via a mechanism facilitated by ATP, this process impaired persistent pulmonary hypertension of newborn (PPHN). observed iHSP70 interacts with mitochondria. Interruption...
We conducted a post-hoc analysis of early inhaled nitric oxide (iNO)-randomized controlled trial data to identify associations pertinent the management moderate hypoxic respiratory failure in term/late preterm infants. Univariate and multivariate logistic regression analyses were used determine risk factors for progression extracorporeal membrane oxygenation (ECMO)/death. Among 299 enrolled infants, index (OI) <20 at enrollment (odds ratio 0.52, confidence interval (CI) 0.27 0.97) surfactant...
Oxidative stress (OS), inflammation, and endoplasmic reticulum (ER) sequentially occur in bronchopulmonary dysplasia (BPD), all result DNA damage. When damage becomes irreparable, tumor suppressors increase, followed by apoptosis or senescence. Although cellular senescence contributes to wound healing, its persistence inhibits growth. Therefore, we hypothesized that BPD progression. Human autopsy lungs were obtained. Sprague-Dawley rat pups exposed 95% oxygen between postnatal day 1 (P1) P10...