Prospective prevention of neonatal hyperammonaemia in argininosuccinic acidura by arginine therapy

Argininosuccinic aciduria, due to deficiency of argininosuccinic acid lyase, is generally associated with severe neonatal hyperammonaemia and its neurological sequelae. The cases of two siblings with this autosomal recessive disorder are presented. Both infants were preterm and delivered by Caesarean section for maternal pre-eclampsia. The first infant was not diagnosed until after the development of severe hyperammonaemia and, despite adequate treatment with haemodialysis and arginine infusion, remained comatose for a prolonged period. At 20 months she has profound developmental delays and intellectual impairment. The second infant, whose diagnosis was made antenatally by amniotic fluid analysis, was treated with arginine infusion beginning at 32 h of life and never developed hyperammonaemia. We conclude that early recognition and prompt institution of arginine therapy is an effective regimen for the prevention of neonatal hyperammonaemia in argininosuccinic aciduria.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42501/1/10545_2005_Article_BF01805478.pd

Immunohistochemical characteristics of porcine intrahepatic nerves under physiological conditions and after bisphenol A administration

Background: The neurochemistry of hepatic nerve fibres was investigated in large animal models after dietary exposure to the endocrine disrupting compound known as bisphenol A (BPA).   Materials and methods: Antibodies against neuronal peptides were used to study changes in hepatic nerve fibres after exposure to BPA at varying concentrations using standard immunofluorescence techniques. The neuropeptides investigated were substance P (SP), galanin (GAL), pituitary adenylate cyclase activating polypeptide (PACAP), calcitonin gene regulated peptide (CGRP) and cocaine and amphetamine regulated transcript (CART). Immunoreactive nerve fibres were counted in multiple sections of the liver and among multiple animals at varying exposure levels. The data was pooled and presented as mean ± standard error of the mean.   Results: It was found that all of the nerve fibres investigated showed upregulation of these neural markers after BPA exposure, even at exposure levels currently considered to be safe. These results show very dramatic increases in nerve fibres containing the above-mentioned neuropeptides and the altered neurochemical levels may be causing a range of pathophysiological states if the trend of over-expression is extrapolated to developing humans.   Conclusions: This may have serious implications for children and young adults who are exposed to this very common plastic polymer, if the same trends are occurring in humans

A New Constraint on the Escape Fraction in Distant Galaxies Using Gamma-ray Burst Afterglow Spectroscopy

We describe a new method to measure the escape fraction fesc of ionizing radiation from distant star-forming galaxies using the afterglow spectra of long-duration gamma-ray bursts (GRBs). Optical spectra of GRB afterglows allow us to evaluate the optical depth of the host ISM, according to the neutral hydrogen column density N(HI) observed along the sightlines toward the star-forming regions where the GRBs are found. Different from previous effort in searching for faint, transmitted Lyman continuum photons, our method is not subject to background subtraction uncertainties and does not require prior knowledge of either the spectral shape of the host galaxy population or the IGM Lya forest absorption along these GRB sightlines. Because most GRBs occur in sub-L_* galaxies, our study also offers the first constraint on fesc for distant low-mass galaxies that dominate the cosmic luminosity density. We have compiled a sample of 27 GRBs at redshift z>2 for which the underlying N(HI) in the host ISM are known. These GRBs together offer a statistical sampling of the integrated optical depth to ionizing photons along random sightlines from star-forming regions in the host galaxies, and allow us to estimate the mean escape fraction averaged over different viewing angles. We find =0.02\pm 0.02 and place a 95% c.l. upper limit <= 0.075 for these hosts. We discuss possible biases of our approach and implications of the result. Finally, we propose to extend this technique for measuring at z~0.2 using spectra of core-collapse supernovae.Comment: Five journal pages, including one figure; ApJL in pres

Biotin Deficiency in a Patient with Short Bowel Syndrome during Home Parenteral Nutrition

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141489/1/jpen0311.pd

Description of a selection method highly cytotoxic for cystinotic fibroblasts but not normal human fibroblasts

Nephropathic cystinosis is an inherited disorder characterized by a high intralysosomal accumulation of cystine due to a defect in lysosomal cystine transport. Cystine can be specifically loaded into the lysosomal compartment of intact cells by incubating cells with cystine dimethyl ester (CDME). We have applied this methyl ester loading technique to develop a selection method that is highly cytotoxic for cystinotic fibroblasts but not normal human fibroblasts and that is based on the inherent differences in lysosomal cystine transport activity of normal and cystinotic fibroblasts. Thus, only 0–0.03% of fetal cystinotic fibroblasts survive exposure to 2 mM CDME for 20 min whereas 70–80% of normal fetal fibroblasts survive these same conditions. Following transfection of cystinotic fibroblasts with normal human genomic DNA or cDNA, this CDME selection method can be used to select for those cells that have been transformed to the normal phenotype and thus aid in the identification of the gene coding for the lysosomal cystine transport protein.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45541/1/11188_2005_Article_BF01233444.pd

A simple method for determination of plasma and urinary biotin

Measurement of biotin in plasma and urine has been stimulated by recent descriptions of inborn errors of biotin metabolism and by newly recognized causes of biotin deficiency. Biotin determination in physiologic fluids to document these conditions has been hindered by lack of a widely useable assay. This paper presents a method which employs tritium-labelled biotin, avidin, and nitrocellulose filters to measure urinary and plasma biotin in a rapid and simple manner.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23871/1/0000110.pd

Maternal and Cord β-Carotene levels and Their Association with Newborn Hearing Screen Results

Background. β-carotene is one of the few carotenoids that can be endogenously converted to vitamin A, a nutrient essential for inner ear development. While previous studies have identified a protective effect of carotenoids on hearing in adults, the impact of β-carotene on hearing outcomes in neonates is not well understood. The purpose of this study is to investigate the relationship between maternal β-carotene intake, maternal plasma, and umbilical cord plasma β-carotene levels and abnormal Newborn Hearing Screen (NHS) results. Significance of Problem. The prenatal period is critical for auditory development; thus, effectors of auditory development may significantly impact long-term hearing ability. Because maternal nutrition is modifiable, an improved understanding of the relationship between β-carotene levels and hearing outcomes may be relevant for prenatal care recommendations. Hypothesis. We hypothesize that higher levels of β-carotene will be associated with decreased risk of abnormal NHS results. Experimental Design. An IRB-approved study enrolled mother-infant pairs (n=541) at the time of delivery. β-carotene plasma levels were analyzed with HPLC. Maternal intake of β-carotene over the past year was quantified using the validated Harvard Food Frequency Questionnaire. NHS results were obtained from the Electronic Medical Record. Statistical analysis was done using the Mann-Whitney U and logistic regression tests, with p\u3c0.05 considered statistically significant. Results. Of the 541 participants, 8.5% of infants had abnormal NHS results. Higher median maternal β-carotene intake was observed in infants who failed their NHS compared to those who passed (5924 vs. 4722 mcg/day, p=0.019). Higher median maternal plasma levels of both trans- (206 vs. 149 mcg/L, p=0.021) and cis-β-carotene (15.9 vs. 11.2 mcg/L, p=0.015) were observed in infants who failed their NHS. Higher median cord plasma trans β-carotene was observed in infants who failed their NHS (15.5 vs. 8.0 mcg/L, p=0.04). Associations between failed NHS and log-transformed β-carotene intake and serum levels remained in a logistic regression model after adjustment for NICU admission, race/ethnicity, smoking status, maternal age, corrected gestational age, infant sex, and log transformed maternal caloric intake. Conclusion. The observed relationship between higher β-carotene levels and abnormal NHS was unexpected. While other studies suggest both deficient and excessive levels of vitamin A can impact inner ear development, β-carotene levels in our study were not exceptionally high. One possible explanation is that higher maternal β-carotene levels may be indicative of impaired transfer of β-carotene to the fetus. Further study is warranted to better understand the relationship between β-carotene and NHS results.https://digitalcommons.unmc.edu/chri_forum/1063/thumbnail.jp

Hypertensive Disorders of Pregnancy are Associated with Differences in Maternal Serum Concentrations of Arachidonic Acid Metabolites

Background: Hypertensive disorders of pregnancy (HDP), including gestational hypertension, chronic hypertension, and preeclampsia, are a significant cause of maternal morbidity and mortality in the United States. Dysregulation of inflammation is thought to play a role in the development of HDP. Maternal diet has the potential to alter the risk of HDP by modulating inflammation. Arachidonic acid (AA) is a dietary polyunsaturated fatty acid which can be metabolized into both pro- and anti-inflammatory bioactive metabolites. Significance of Problem: HDP places women and their infants at risk for potentially severe pregnancy complications including placental abruption, embolism, end-organ failure, or death. Few treatments are currently available for HDP. Question: The objective of this study was to describe how maternal AA metabolites serum concentrations are associated with diagnosis of HDP. Experimental Design: Serum was collected from 121 pregnant women admitted to the labor and delivery unit at Nebraska Medical Center. Women were divided into normotensive or hypertensive groups based on definitions from the American College of Obstetricians and Gynecologists (ACOG). Concentrations of AA metabolites were measured using liquid chromatography-mass spectrometry. Descriptive statistics were generated, and Mann-Whitney U tests were used to compare metabolite concentrations between groups. Results: Women with HDP had significant higher serum concentrations of PGF2α (p=0.02) and 15-HETE (p=0.04), two metabolites with known inflammatory and vasoconstrictive properties. Women with HDP had significantly lower serum concentrations of 8(9)-DiHET (p=0.04), 11(12)-DiHET (p=0.04), and 14(15)-DiHET (p=0.001), which are all associated with vasodilation. Unexpectantly, hypertensive mothers also had lower serum concentrations of 5-HETE (p=0.02), which is associated with vasoconstriction. Conclusion: Overall, our study reveals that mothers diagnosed with HDP had significantly higher serum concentrations of vasoconstrictive AA metabolites and significantly lower serum concentrations of vasodilating AA metabolites compared to normotensive mothers. Future directions include analyzing differences in maternal metabolite profile separately for mothers with chronic hypertension, gestational hypertension, and preeclampsia compared to normotensive mothers. Results from these analyses will guide nutritional recommendations for women at risk of developing HDP.https://digitalcommons.unmc.edu/chri_forum/1062/thumbnail.jp

On the offset of Short Gamma-ray Bursts

Short Gamma-Ray Bursts (SGRBs) are expected to form from the coalescence of compact binaries, either of primordial origin or from dynamical interactions in globular clusters. In this paper, we investigate the possibility that the offset and afterglow brightness of a SGRB can help revealing the origin of its progenitor binary. We find that a SGRB is likely to result from the primordial channel if it is observed within 10 kpc from the center of a massive galaxy and shows a detectable afterglow. The same conclusion holds if it is 100 kpc away from a small, isolated galaxy and shows a weak afterglow. On the other hand, a dynamical origin is suggested for those SGRBs with observable afterglow either at a large separation from a massive, isolated galaxy or with an offset of 10-100 kpc from a small, isolated galaxy. We discuss the possibility that SGRBs from the dynamical channel are hosted in intra-cluster globular clusters and find that GRB 061201 may fall within this scenario.Comment: 5 pages, 3 figures, MNRAS in pres

Discovery of the broad-lined Type Ic SN 2013cq associated with the very energetic GRB 130427A

Long-duration gamma-ray bursts (GRBs) at z < 1 are in most cases found to be accompanied by bright, broad-lined Type Ic supernovae (SNe Ic-BL). The highest-energy GRBs are mostly located at higher redshifts, where the associated SNe are hard to detect observationally. Here we present early and late observations of the optical counterpart of the very energetic GRB 130427A. Despite its moderate redshift z = 0.3399+/-0.0002, GRB 130427A is at the high end of the GRB energy distribution, with an isotropic-equivalent energy release of Eiso ~ 9.6x10^53 erg, more than an order of magnitude more energetic than other GRBs with spectroscopically confirmed SNe. In our dense photometric monitoring, we detect excess flux in the host-subtracted r-band light curve, consistent with what expected from an emerging SN, ~0.2 mag fainter than the prototypical SN 1998bw. A spectrum obtained around the time of the SN peak (16.7 days after the GRB) reveals broad undulations typical of SNe Ic-BL, confirming the presence of a SN, designated SN 2013cq. The spectral shape and early peak time are similar to those of the high expansion velocity SN 2010bh associated with GRB 100316D. Our findings demonstrate that high-energy long-duration GRBs, commonly detected at high redshift, can also be associated with SNe Ic-BL, pointing to a common progenitor mechanism.Comment: 12 pages, 4 figures, 1 table, accepted for publication in Ap