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Your search keyword '"Terrance J. Kavanagh"' showing total 4 results
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4 results on '"Terrance J. Kavanagh"'

1. Persistence of improved glucose homeostasis in Gclm null mice with age and cadmium treatment

Author

Christopher M. Schaupp, Dianne Botta, Collin C. White, David K. Scoville, Sengkeo Srinouanprachanh, Theo K. Bammler, James MacDonald, and Terrance J. Kavanagh

Subjects
Glutathione, NRF2, Diabetes, Glucose homeostasis, Insulin resistance, Aging, Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

Antioxidant signaling/communication is among the most important cellular defense and survival pathways, and the importance of redox signaling and homeostasis in aging has been well-documented. Intracellular levels of glutathione (GSH), a very important endogenous antioxidant, both govern and are governed by the Nrf2 pathway through expression of genes involved in its biosynthesis, including the subunits of the rate-limiting enzyme (glutamate cysteine ligase, GCL) in GSH production, GCLC and GCLM. Mice homozygous null for the Gclm gene are severely deficient in GSH compared to wild-type controls, expressing approximately 10% of normal GSH levels. To compensate for GSH deficiency, Gclm null mice have upregulated redox-regulated genes, and, surprisingly, are less susceptible to certain types of oxidative damage. Furthermore, young Gclm null mice display an interesting lean phenotype, resistance to high fat diet-induced diabetes and obesity, improved insulin and glucose tolerance, and decreased expression of genes involved in lipogenesis. However, the persistence of this phenotype has not been investigated into old age, which is important in light of studies which suggest aging attenuates antioxidant signaling, particularly in response to exogenous stimuli. In this work, we addressed whether aging compromises the favorable phenotype of increased antioxidant activity and improved glucose homeostasis observed in younger Gclm null mice. We present data showing that under basal conditions and in response to cadmium exposure (2 mg/kg, dosed once via intraperitoneal injection), the phenotype previously described in young (

Published
2022
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3. Associations between repeated measures of urinary phthalate metabolites and biomarkers of oxidative stress in a rural agricultural cohort of children with asthma

Author

Ryan S. Babadi, Anne M. Riederer, Paul D. Sampson, Sheela Sathyanarayana, Terrance J. Kavanagh, Jennifer E. Krenz, Syam S. Andra, Seunghee Kim-Schulze, Karen L. Jansen, Elizabeth Torres, Adriana Perez, Lisa R. Younglove, Maria I. Tchong-French, and Catherine J. Karr

Subjects
Environmental Engineering, Phthalic Acids, Agriculture, DNA, Environmental Exposure, Pollution, Asthma, Oxidative Stress, 8-Hydroxy-2'-Deoxyguanosine, Diethylhexyl Phthalate, Humans, RNA, Environmental Chemistry, Environmental Pollutants, Child, Waste Management and Disposal, Biomarkers
Abstract

Phthalate exposure is widespread, and studies suggest an adverse relationship with asthma morbidity, including some support for oxidative stress as an underlying pathophysiological mechanism. Urinary phthalate metabolites have been associated with biomarkers of oxidative stress, but data are few in children diagnosed with asthma. We used participant data from the Home Air in Agriculture Pediatric Intervention Trial (HAPI) to examine longitudinal relationships between phthalates and oxidative stress in a cohort of Latino children with asthma residing in an agricultural community. We used linear mixed-effects models to estimate associations between 11 urinary phthalate metabolites (and one summed measure of di-2-ethylhexyl phthalate (DEHP) metabolites, ∑DEHP) and two urinary biomarkers of oxidative stress: a biomarker of lipid peroxidation via measure of 8-isoprostane and a biomarker of DNA/RNA oxidative damage via combined measure of 8-hydroxydeoxyguanosine (8-OHdG), 8-hydroxyguanosine (8-OHG), and 8-hydroxyguanine. Seventy-nine participants provided 281 observations. In covariate-adjusted models, we observed significant positive relationships between all phthalate metabolites and 8-isoprostane, effect sizes ranging from a 9.3 % (95 % CI: 4.2 %-14.7 %) increase in 8-isoprostane for each 100 % increase (i.e., doubling) of mono-(carboxy-isooctyl) phthalate (MCIOP), to a 21.0 % (95 % CI: 14.3 %-28.2 %) increase in 8-isoprostane for each doubling of mono-n-butyl phthalate (MNBP). For each doubling of mono-(carboxy-isononyl) phthalate (MCINP) and mono-ethyl phthalate (MEP), the DNA/RNA oxidative damage biomarker increased by 6.0 % (95 % CI: 0.2 %-12.2 %) and 6.5 % (95 % CI: 1.4 %-11.9 %), respectively. In conclusion, we provide unique data suggesting phthalate exposure is positively associated with oxidative stress in children with asthma. Our repeat measures provide novel identification of a consistent effect of phthalates on oxidative stress in children with asthma via lipid peroxidation. Confirmation in future studies of children with asthma is needed to enhance understanding of the role of phthalates in childhood asthma morbidity.

Published
2022

4. Longitudinal measures of phthalate exposure and asthma exacerbation in a rural agricultural cohort of Latino children in Yakima Valley, Washington

Author

Ryan S. Babadi, Anne M. Riederer, Paul D. Sampson, Sheela Sathyanarayana, Terrance J. Kavanagh, Jennifer E. Krenz, Syam S. Andra, Seunghee Kim-Schulze, Karen L. Jansen, Elizabeth Torres, Adriana Perez, Lisa R. Younglove, Maria I. Tchong-French, and Catherine J. Karr

Subjects
Washington, Phthalic Acids, Public Health, Environmental and Occupational Health, Humans, Agriculture, Environmental Pollutants, Environmental Exposure, Hispanic or Latino, Child, Asthma
Abstract

Phthalates are a class of widely used synthetic chemicals found in commonly used materials and products. Epidemiological studies suggest phthalate exposure is associated with asthma outcomes, though most studies have not investigated phthalates as triggers of exacerbations in children diagnosed with asthma. This study used data from the Home Air in Agriculture Pediatric Intervention Trial (HAPI) to examine relationships between phthalate exposure and outcomes related to childhood asthma exacerbation. We used measures of phthalate metabolites and respiratory health measures including fractional exhaled nitric oxide (FENO), the Asthma Control Test (ACT), caregiver report of symptoms, and urinary leukotriene E

Published
2022

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