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"Adelman, Heidi"
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Choline Supplementation Does Not Promote Atherosclerosis in CETP-Expressing Male Apolipoprotein E Knockout Mice
Dietary trimethylamines, such as choline, metabolized by intestinal microbiota to trimethylamine are absorbed by the gut and oxidized to trimethylamine N-oxide (TMAO). The objective of this study was to determine the effect of choline supplementation on atherosclerosis progression in Apoe−/− mice expressing human cholesterol ester transfer protein (hCETP) using the same diets as in previously reported studies. Mice expressing hCETP, after transfection with AAV2/8-hCETP, were fed an 18% protein diet with either 0.09% (standard chow), 0.5% or 1% choline for 16 weeks. Control mice not transfected with hCETP were fed 1% choline. Dietary choline supplementation increased plasma TMAO levels at 8 and 16 weeks. When atherosclerotic lesions were measured in the thoracic aorta and aortic root, there were no differences between any of the treatment groups in the amount of plaque development at either site. Throughout the study, no significant changes in plasma lipids or major classes of lipoproteins were observed in hCETP-expressing mice. Plasma-oxidized low density lipoprotein, myeloperoxidase and high density lipoprotein inflammatory index were measured at 16 weeks, with no significant changes in any of these inflammatory markers between the four treatment groups. Despite increasing plasma TMAO levels, dietary choline supplementation in Apoe−/− mice expressing hCETP did not promote atherosclerosis.
Journal Article
Binding Folate Receptor Alpha Autoantibody Is a Biomarker for Leucovorin Treatment Response in Autism Spectrum Disorder
Autism spectrum disorder (ASD) affects up to 1 in 36 children in the United States. It is a heterogeneous neurodevelopmental disorder with life-long consequences. Patients with ASD and folate pathway abnormalities have demonstrated improved symptoms after treatment with leucovorin (folinic acid), a reduced form of folate. However, biomarkers for treatment response have not been well investigated and clinical trials are lacking. In this retrospective analysis, a cohort of prospectively collected data from 110 consecutive ASD clinic patients [mean (SD) age: 10.5 (6.2) years; 74% male] was examined. These patients all underwent testing for folate receptor alpha autoantibodies (FRAAs) and soluble folate binding proteins (sFBPs) biomarkers and were treated with leucovorin, if appropriate. Analyses examined whether these biomarkers could predict response to leucovorin treatment as well as the severity of ASD characteristics at baseline. The social responsiveness scale (SRS), a measure of core ASD symptoms, and the aberrant behavior checklist (ABC), a measure of disruptive behavior, were collected at each clinic visit. Those positive for sFBPs had more severe ASD symptoms, and higher binding FRAA titers were associated with greater ABC irritability. Treatment with leucovorin improved most SRS subscales with higher binding FRAA titers associated with greater response. Leucovorin treatment also improved ABC irritability. These results confirm and expand on previous studies, underscore the need for biomarkers to guide treatment of folate pathways in ASD, and suggest that leucovorin may be effective for children with ASD.
Journal Article
The Soluble Folate Receptor in Autism Spectrum Disorder: Relation to Autism Severity and Leucovorin Treatment
Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder with life-long consequences that affects up to 1 in 44 children. Treatment with leucovorin (folinic acid), a reduced form of folate, has been shown to improve symptoms in those with ASD and folate pathway abnormalities in controlled clinical trials. Although soluble folate binding proteins (sFBPs) have been observed in the serum of some patients with ASD, the significance of this finding has not been studied. Here, we present a cohort of ASD patients with sFBPs. These patients had severe ASD and were medically complex. Using baseline controlled open-label methodology and standardized assessments, these patients were found to improve in both core and associated ASD symptoms with leucovorin treatment. No adverse effects were related to leucovorin treatment. This is the first report of the sFBPs in ASD. This study complements ongoing controlled clinical trials and suggests that leucovorin may be effective for children with ASD who are positive for sFBPs. Further, sFBPs might be important biomarkers for treatment response to leucovorin in children with ASD. This study paves the way for further controlled studies for patients with sFBPs.
Journal Article
Sloan Digital Sky Survey Multicolor Observations of GRB010222
The discovery of an optical counterpart to GRB010222 (detected by BeppoSAX; Piro 2001) was announced 4.4 hrs after the burst by Henden (2001a). The Sloan Digital Sky Survey's 0.5m photometric telescope (PT) and 2.5m survey telescope were used to observe the afterglow of GRB010222 starting 4.8 hours after the GRB. The 0.5m PT observed the afterglow in five, 300 sec g' band exposures over the course of half an hour, measuring a temporal decay rate in this short period of F_nu t^-1.0+/-0.5. The 2.5m camera imaged the counterpart nearly simultaneously in five filters (u' g' r' i' z'), with r' = 18.74+/-0.02 at 12:10 UT. These multicolor observations, corrected for reddening and the afterglow's temporal decay, are well fit by the power-law F_nu nu^-0.90+/-0.03 with the exception of the u' band UV flux which is 20% below this slope. We examine possible interpretations of this spectral shape, including source extinction in a star forming region.
Paper