Judy Aschner | Albert Einstein College of Medicine - Yeshiva University (original) (raw)

Papers by Judy Aschner

Thromboxane inhibition reduces an early stage of chronic hypoxiainduced pulmonary hypertension in... more Thromboxane inhibition reduces an early stage of chronic hypoxiainduced pulmonary hypertension in piglets. The pulmonary vasoconstrictor, thromboxane, may contribute to the development of pulmonary hypertension. Our objective was to determine whether a combined thromboxane synthase inhibitor-receptor antagonist, terbogrel, prevents pulmonary hypertension and the development of aberrant pulmonary arterial responses in newborn piglets exposed to 3 days of hypoxia. Piglets were maintained in room air (control) or 11% O2 (hypoxic) for 3 days. Some hypoxic piglets received terbogrel (10 mg/kg po bid). Pulmonary arterial pressure, pulmonary wedge pressure, and cardiac output were measured in anesthetized animals. A cannulated artery technique was used to measure responses to acetylcholine. Pulmonary vascular resistance for terbogrel-treated hypoxic piglets was almost one-half the value of untreated hypoxic piglets but remained greater than values for control piglets. Dilation to acetylcholine in preconstricted pulmonary arteries was greater for terbogrel-treated hypoxic than for untreated hypoxic piglets, but it was less for pulmonary arteries from both groups of hypoxic piglets than for control piglets. Terbogrel may ameliorate pulmonary artery dysfunction and attenuate the development of chronic hypoxia-induced pulmonary hypertension in newborns.

Biological trace element research, 2002

Previous studies have shown that iron deficiency (ID) increases brain manganese (Mn), but specifi... more Previous studies have shown that iron deficiency (ID) increases brain manganese (Mn), but specific regional changes have not been addressed. Weanling rats were fed one of three semipurified diets: control (CN), iron deficient (ID), or iron deficient/manganese fortified (IDMn+). Seven brain regions were analyzed for Mn concentration and amino acid (glutamate, glutamine, taurine, gamma-aminobutyric acid) concentrations. Both ID and IDMn+ diets caused significant (p<0.05) increases in Mn concentration across brain regions compared to CN. The hippocampus was the only brain region in which the IDMn+ group accumulated significantly more Mn than both the CN and ID groups. ID significantly decreased GABA concentration in hippocampus, caudate putamen, and globus pallidus compared to CN rats. Taurine was significantly increased in the substantia nigra of the IDMn+ group compared to both ID and CN. ID also altered glutamate and glutamine concentrations in cortex, caudate putamen, and thalam...

Journal of child neurology, 2015

Caffeine, standard treatment for apnea of prematurity, improves brainstem auditory processing. We... more Caffeine, standard treatment for apnea of prematurity, improves brainstem auditory processing. We hypothesized that caffeine also improves cortical differentiation of complex speech sounds. We used event-related potential methodology to measure responses to speech-sound contrasts in 45 intensive care neonates, stratified by cumulative exposure as no-, low-, and high-caffeine groups. Sound differentiation in the low-caffeine group and near-term no-caffeine infants was similar with repeated measures analysis of variance controlling for gestational and postnatal age. However, a generalized estimating equation approach demonstrated that, at equivalent postnatal age, differentiation was reduced in the high-caffeine (gestational age 25 weeks) compared to the low-caffeine group (gestational age 28 weeks), reflecting the importance of maturity at birth (Z = 2.77, P < .006). We conclude that caffeine improves measures of auditory processing associated with improved neurodevelopmental outc...

Biological Trace Element Research, 2005

Thimerosal, also known as thimersal, Merthrolate, or sodiumethyl-mercurithiosalicylate, is an org... more Thimerosal, also known as thimersal, Merthrolate, or sodiumethyl-mercurithiosalicylate, is an organic mercurial compound that is used in a variety of commercial as well as biomedical applications. As a preservative, it is used in a number of vaccines and pharmaceutical products. Its active ingredient is ethylmercury. Both inorganic and organic mercurials are known to interfere with glutamate homeostasis. Brain glutamate is removed mainly by astrocytes from the extracellular fluid via high-affinity astroglial Na+-dependent excitatory amino acid transporters, glutamate/ aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1). The effects of thimerosal on glutamate homeostasis have yet to be determined. As a first step in this process, we examined the effects of thimerosal on the transport of [3H]-d-aspartate, a nonmetabolizable glutamate analog, in Chinese hamster ovary (CHO) cells transfected with two glutamate transporter subtypes, GLAST (EAAT1) and GLT-1 (EAAT2). Additionally, studies were undertaken to determine the effects of thimerosal on mRNA and protein levels of these transporters. The results indicate that thimerosal treatment caused significant but selective changes in both glutamate transporter mRNA and protein expression in CHO cells. Thimerosal-mediated inhibition of glutamate transport in the CHO-K1 cell line DdB7 was more pronounced in the GLT-1-transfected cells compared with the GLAST- transfected cells. These studies suggest that thimerosal accumulation in the central nervous system might contribute to dysregulation of glutamate homeostasis.

The Journal of pediatrics, 2014

A cademic pediatrics is motivated by a vision wherein tomorrow's children are healthier and more ... more A cademic pediatrics is motivated by a vision wherein tomorrow's children are healthier and more able to realize their full potential than today's children. To realize this aspiration, pediatrics in general, and academic pediatrics in particular, serves as a guardian of: (1) a body of knowledge, which must be gained by experience and communicated to the next generation; (2) a code of ethics, which entails service to our patients and our students; and (3) a set of standards, which must be used to protect our patients and their futures. The goal that "tomorrow's care must be superior to today's approaches" mandates academic pediatricians to maintain vigorous and diverse research programs, even while advocating and caring for children and their families. 1 Sustained progress entails teaching the next generation of pediatricians, creating new knowledge, and translating this new knowledge into improved, compassionate care. At the centerpiece of these efforts is the physician-scientist, uniquely well positioned to teach, create, care, and translate. Physician-scientists devote substantial efforts to research that creates new knowledge across the entire spectrum of biomedical inquiry. Successful development and application of novel therapies requires investigators with expertise in multiple disciplines to be effectively organized. 2,3 Creation of durable knowledge demands testing at the bedside as well as in the laboratory. Academic pediatrics requires pediatrician-scientists to span the ever-widening distance between practicing clinicians and fundamental scientific disciplines including health services and policy research. Welltrained pediatrician-scientists are uniquely equipped to pose clinically relevant questions that can link the biomedical disciplines to the bedside care of children. Unfortunately, over the last 30 years, as resources and discretionary time have become increasingly scarce, proportionately fewer physician-scientists have committed to a research-based career. Since the 1980s, the percentage of physicians dedicating significant components of their professional lives to research has declined from approximately 5% to 1.5%. 5 Despite training more physicians, the absolute number of physician-scientists is both declining and aging. The relative percentage of research program grants awarded to MDs over 50 years of age increased from 25% in 1980 to greater than 50% at present. 5 To apply the power of biologic discovery to human health, the supply of physician-scientists must be sustained and replenished.

Nitric oxide (NO) is crucial in diverse physiological and pathological processes. We show that a ... more Nitric oxide (NO) is crucial in diverse physiological and pathological processes. We show that a hypomorphic mouse model of argininosuccinate lyase (encoded by Asl) deficiency has a distinct phenotype of multiorgan dysfunction and NO deficiency. Loss of Asl in both humans and mice leads to reduced NO synthesis, owing to both decreased endogenous arginine synthesis and an impaired ability to

Toxicological Sciences, 2007

Excessive free radical formation has been implicated as a causative factor in neurotoxic damage a... more Excessive free radical formation has been implicated as a causative factor in neurotoxic damage associated with exposures to a variety of metals, including manganese (Mn). It is well established that Mn accumulates in astrocytes, affecting their ability to indirectly induce and/or exacerbate neuronal dysfunction. The present study examined the effects of Mn treatment on the following endpoints in primary astrocyte cultures: (1) oxidative injury, (2) alterations in high-energy phosphate (adenosine 5#-triphosphate, ATP) levels, (3) mitochondrial inner membrane potential, and (4) glutamine uptake and the expression of glutamine transporters. We quantified astrocyte cerebral oxidative damage by measuring F 2 -isoprostanes (F 2 -IsoPs) using stable isotope dilution methods followed by gas chromatography-mass spectrometry with selective ion monitoring. Our data showed a significant ( p < 0.01) elevation in F 2 -IsoPs levels at 2 h following exposure to Mn (100mM, 500mM, or 1mM). Consistent with this observation, Mn induced a concentration-dependent reduction in ATP and the inner mitochondrial membrane potential (DÉ m ), measured by the high pressure liquid chromatography method and the potentiometric dye, tetramethyl rhodamine ethyl ester, respectively. Moreover, 30 min of pretreatment with Mn (100mM, 500mM, or 1mM) inhibited the net uptake of glutamine (GLN) ( 3 H-glutamine) measured at 1 and 5 min. Expression of the messenger RNA coding the GLN transporters, SNAT3/SN1 and SNAT1, was inhibited after 100 and 500mM Mn treatment for 24 h. Our results demonstrate that induction of oxidative stress, associated mitochondrial dysfunction, and alterations in GLN/glutamate cycling in astrocytes represent key mechanisms by which Mn exerts its neurotoxicity.

Psychophysiology, 2012

The study examined the effect of gestational (GA) and postnatal (PNA) age on speech sound percept... more The study examined the effect of gestational (GA) and postnatal (PNA) age on speech sound perception in infants. Auditory ERPs were recorded in response to speech sounds (CV syllables) in 50 infant NICU patients (born at 24-40 weeks gestation) prior to discharge. Efficiency of speech perception was quantified as absolute difference in mean amplitudes of ERPs in response to vowel (/a/-/u/) and consonant (/b/-/g/, /d/-/g/) contrasts within 150-250, 250-400, 400-700 ms after stimulus onset. Results indicated that both GA and PNA affected speech sound processing. These effects were more pronounced for consonant than vowel contrasts. Increasing PNA was associated with greater sound discrimination in infants born at or after 30 weeks GA, while minimal PNA-related changes were observed for infants with GA less than 30 weeks. Our findings suggest that a certain level of brain maturity at birth is necessary to benefit from postnatal experience in the first 4 months of life, and both gestational and postnatal ages need to be considered when evaluating infant brain responses.

PLoS ONE, 2014

Rationale: There is evidence that impairments in nitric oxide (NO) signaling contribute to chroni... more Rationale: There is evidence that impairments in nitric oxide (NO) signaling contribute to chronic hypoxia-induced pulmonary hypertension. The L-arginine-NO precursor, L-citrulline, has been shown to ameliorate pulmonary hypertension. Sodium-coupled neutral amino acid transporters (SNATs) are involved in the transport of L-citrulline into pulmonary arterial endothelial cells (PAECs). The functional link between the SNATs, L-citrulline, and NO signaling has not yet been explored.

Pharmacology & Therapeutics, 2007

Manganese (Mn) is an essential trace metal found in all tissues, and it is required for normal am... more Manganese (Mn) is an essential trace metal found in all tissues, and it is required for normal amino acid, lipid, protein, and carbohydrate metabolism. While Mn deficiency is extremely rare in humans, toxicity due to overexposure of Mn is more prevalent. The brain appears to be especially vulnerable. Mn neurotoxicity is most commonly associated with occupational exposure to aerosols or dusts that contain extremely high levels (> 1-5 mg Mn/m 3 ) of Mn, consumption of contaminated well water, or parenteral nutrition therapy in patients with liver disease or immature hepatic functioning such as the neonate.

PEDIATRICS, 2003

To determine whether the use of the Infant Flow continuous positive airway pressure (IF CPAP) sys... more To determine whether the use of the Infant Flow continuous positive airway pressure (IF CPAP) system reduces the rate of extubation failure among extremely low birth weight (ELBW) infants (infants with birth weight &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;1000 g) when compared with conventional CPAP delivered with a conventional ventilator and nasal prongs. A prospective, unmasked, randomized, controlled clinical trial was conducted in 162 eligible intubated ELBW infants who were hospitalized in 2 intensive care nurseries in Winston-Salem, North Carolina, between July 1997 and November 2000. Successful extubation was defined as no need for reintubation for any reason for at least 7 days after the first extubation attempt. The individual extubation success rates were 61.9% (52 of 84) in the conventional CPAP group and 61.5% (48 of 78) in the IF CPAP group. There were no significant differences in the extubation success rate in any birth weight subset between the 2 cohorts. The most common cause of extubation failure was apnea/bradycardia. Infants who were randomized to IF CPAP had fewer days on supplemental O(2) and shorter hospital stays. Extubation failure is a common problem, occurring in nearly 40% of ELBW infants who require mechanical ventilation. IF CPAP was as effective but no more effective than conventional CPAP in preventing extubation failure among ELBW infants. New strategies are needed to identify predictors of extubation success and to treat apnea/bradycardia, the most common cause of extubation failure, thereby reducing the likelihood of prolonged intubation in this high-risk cohort of premature infants.

Pediatric Research, 2013

Abnormal heart rate characteristics (HRC) wax and wane in early stages of culture-positive, late-... more Abnormal heart rate characteristics (HRC) wax and wane in early stages of culture-positive, late-onset septicemia (LOS) in patients in the neonatal intensive care unit (NICU). Continuously monitoring an HRC index leads to a reduction in mortality among very low birth weight (VLBW) infants. We hypothesized that the reduction in mortality was due to a decrease in septicemia-associated mortality. This is a secondary analysis of clinical and HRC data from 2,989 VLBW infants enrolled in a randomized clinical trial of HRC monitoring in nine NICUs from 2004 to 2010. LOS was diagnosed 974 times in 700 patients, and the incidence and distribution of organisms were similar in HRC display and nondisplay groups. Mortality within 30 d of LOS was lower in the HRC display as compared with the nondisplay group (11.8 vs. 19.6%; relative risk: 0.61; 95% confidence interval: 0.43, 0.87; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01), but mortality reduction was not statistically significant for patients without LOS. There were fewer large, abrupt increases in the HRC index in the days leading up to LOS diagnosis in infants whose HRC index was displayed. Continuous HRC monitoring is associated with a lower septicemia-associated mortality in VLBW infants, possibly due to diagnosis earlier in the course of illness.

New England Journal of Medicine, 2002

New England Journal of Medicine, 2013

To the Editor: We are a group of scholars and leaders in bioethics and pediatrics with extensive ... more To the Editor: We are a group of scholars and leaders in bioethics and pediatrics with extensive experience in ethical and regulatory issues in pediatrics and human subjects research. We urge the Office for Human Research Protections (OHRP) to withdraw its notification to the institutions involved in the Surfactant, Positive Pressure, and Oxygenation Randomized Trial (SUPPORT) that they failed to meet regulatory informed-consent requirements, in particular regarding reasonably foreseeable risks of enrollment in the study. We believe that this conclusion was a substantive error and will have adverse implications for future research.

NeuroToxicology, 2006

Manganese (Mn), an element found in many foods, is an important and essential nutrient for proper... more Manganese (Mn), an element found in many foods, is an important and essential nutrient for proper health and maintenance. It is toxic in high doses, however, and exposure to excessive levels can result in the onset of a neurological disorder similar to, but distinct from, Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease. Historically, Mn neurotoxicity was most commonly associated with various occupations, such as Mn mining, welding and steel production. More recently, increases in both blood and brain Mn levels have been observed in persons with liver disease or those receiving prolonged parenteral nutrition. Additionally, rodent data suggest that iron deficiency and anemia may be risk factors for Mn neurotoxicity. Clinically, brain Mn accumulation can be monitored in vivo using non-invasive magnetic resonance imaging (MRI) due to the paramagnetic nature of this element. Indeed, MRI has been used in a variety of settings to evaluate the brain Mn deposition in various populations. This review focuses on the use of MRI technology in studies related specifically to Mn neurotoxicity. Thus, we will examine reports using MRI to confirm brain Mn accumulation in human populations, and conclude with data from non-human primate and rodent models of Mn neurotoxicity.

Journal of Perinatology, 2005

Journal of Perinatology, 2001

To evaluate the feasibility of conducting a prospective, randomized trial comparing early high -f... more To evaluate the feasibility of conducting a prospective, randomized trial comparing early high -frequency oscillatory ventilation ( HFOV ) to synchronized intermittent mandatory ventilation ( SIMV ) in very low birth weight ( VLBW ) premature infants. This pilot study evaluated two ventilator management protocols to determine how well they could be implemented in a multicenter clinical trial.