The Experts below are selected from a list of 16452 Experts worldwide ranked by ideXlab platform
Jason D Morrow - One of the best experts on this subject based on the ideXlab platform.
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Increased oxidative stress in patients with depression and its relationship to treatment.
Psychiatry research, 2012Co-Authors: Cecilia P Chung, Jason D Morrow, Dennis Schmidt, Charles Michael Stein, Ronald M SalomonAbstract:Oxidative stress may play a role in the pathogenesis of depression. We tested the hypothesis that urinary F2 Isoprostanes, a robust marker of oxidative stress, was increased in patients with depression and associated with symptoms and response to treatment. Urinary F2 Isoprostanes was compared in 18 patients with depression and 36 age and sex matched control subjects. In patients, we tested the association between oxidative stress, depression questionnaires and antidepressant treatment. Urinary F2 Isoprostane excretion was significantly higher in patients with depression than in control subjects. This association remained significant after adjustment for age, sex and BMI. Depression symptom severity scores were not correlated with F2 Isoprostane excretion. Nine patients were treated with sertraline or bupropion for 8 weeks. Depression severity rating scale scores decreased significantly and F2 Isoprostane excretion increased. The increase in F2 Isoprostane excretion was inversely correlated with the improvement in Hamilton Depression Rating 17 items. In conclusion, oxidative stress is increased in patients with depression. However, although treatment with either bupropion or sertraline reduces the symptoms of depression, it may increase F2 Isoprostane excretion. These results suggest that alternative mechanisms, beyond oxidative stress, may be involved in the development of depression and subsequent responses to treatment.
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oxidative stress measured by urine f2 Isoprostane level is associated with prostate cancer
The Journal of Urology, 2011Co-Authors: Daniel A Barocas, Jackson L Roberts, Jason D Morrow, Ginger L Milne, Saundra Motley, Michael S Cookson, Sam S Chang, David F Penson, Qi Dai, Raoul S ConcepcionAbstract:Purpose: Oxidative stress is implicated in prostate cancer by several lines of evidence. We studied the relationship between the level of F2-Isoprostanes, a validated biomarker of oxidative stress, and prostate cancer and high grade prostatic intraepithelial neoplasia.Materials and Methods: This case-control analysis within the Nashville Men's Health Study included men recruited at prostate biopsy. Body morphometrics, health history and urine were collected from more than 2,000 men before biopsy. F2-Isoprostanes were measured by gas chromatography/mass spectrometry within an age matched sample of Nashville Men's Health Study participants that included 140 patients with high grade prostatic intraepithelial neoplasia, 160 biopsy negative controls and 200 prostate cancer cases. Multivariable linear and logistic regression was used to determine the associations between F2-Isoprostane level, and high grade prostatic intraepithelial neoplasia and prostate cancer.Results: Mean patient age was 66.9 years (SD 7.2)...
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separation and identification of f2 Isoprostane regioisomers and diastereomers by novel liquid chromatographic mass spectrometric methods
Journal of Chromatography B, 2005Co-Authors: Huiyong Yin, Ned A Porter, Jason D MorrowAbstract:Isoprostanes are isomers of prostaglandins that are generated from free radical-initiated autoxidation of arachidonic acid. Quantification of F2-Isoprostanes is regarded as the “gold standard” to assess oxidative stress in various human diseases. There are 32 possible racemic Isoprostane isomers that exist as four sets of regioisomers. Each regioisomer is composed of eight diastereomers. We report liquid chromatographic/mass spectrometric methods to separate and identify F2-Isoprostane stereoisomers. These methods have been applied to the analysis of F2-Isoprostanes derived from tissues of rats exposed to an oxidative stress and are useful to assess the relative formation of various regioisomers and stereoisomers generated in vitro and in vivo. The delineation of the more abundant isomers formed will allow for studies to examine the biological relevance of selected compounds in vivo.
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Degree of heteroplasmy reflects oxidant damage in a large family with the mitochondrial DNA A8344G mutation
Free radical biology & medicine, 2005Co-Authors: Jeffrey A. Canter, Jason D Morrow, Joshua P Fessel, Alex Eshaghian, Marshall L. Summar, Jackson Ii L Roberts, James E. Sligh, Jonathan L. HainesAbstract:Mitochondria are the source of most oxygen-derived free radicals. Mutations in mitochondrial DNA can impair mitochondrial electron transport resulting in decreased ATP production and increased free radical-induced oxidant injury. The specific mitochondrial DNA mutation A8344G alters the TPsiC loop or the mitochondrial tRNA for lysine. We investigated a large five-generational family harboring this mutation to determine whether the degree of heteroplasmy (proportion of mutated mitochondrial genomes) for the mtA8344G mutation correlated with a marker of oxidant damage. We measured F2-Isoprostanes because they are specific and reliable markers of oxidant injury formed when free radicals attack esterified arachidonate in cell membranes. Family members with high heteroplasmy (>40%) had significantly higher F2-Isoprostane levels (62 +/- 39 pg/ml) than those with lower heteroplasmy (33 +/- 13 pg/ml, P < 0.001). The degree of heteroplasmy for the mtA8344G mutation in this family correlated positively with F2-Isoprostane levels (P = 0.03). This study highlights the underappreciated role free radicals play in the complex pathophysiology of inherited mitochondrial DNA disorders. The most important novel finding from this family is that some currently asymptomatic individuals with moderate heteroplasmy have evidence of ongoing free-radical mediated oxidant injury.
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F2-Isoprostanes as markers of oxidant stress: an overview.
Current protocols in toxicology, 2005Co-Authors: Erik S Musiek, Jason D MorrowAbstract:The Isoprostanes are a unique series of prostaglandin-like compounds formed in vivo via a non-enzymatic mechanism involving the free radical-initiated peroxidation of arachidonic acid. This unit summarizes selected aspects regarding current knowledge of these compounds and their value as markers of oxidative injury. Novel aspects related to the biochemistry of Isoprostane formation are discussed and methods by which these compounds can be analyzed and quantified are summarized. A considerable portion of this unit examines the utility of F(2)-Isoprostanes as markers of oxidant injury in vitro and in vivo. Numerous studies carried out over the past decade have shown that these compounds are extremely accurate measures of lipid peroxidation in animals and humans and have illuminated the role of oxidant injury in a number of human diseases.
Apparao B Kummarapurugu - One of the best experts on this subject based on the ideXlab platform.
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nadph quinone oxidoreductase 1 regulates host susceptibility to ozone via Isoprostane generation
Journal of Biological Chemistry, 2013Co-Authors: Apparao B Kummarapurugu, Bernard M Fischer, Shuo Zheng, Ginger L Milne, Andrew J Ghio, Erin N Pottskant, Michael W Foster, Erik J Soderblom, Laura G Dubois, Arthur M MoseleyAbstract:Abstract NADPH quinone oxidoreductase 1 (NQO1) is recognized as a major susceptibility gene for ozone-induced pulmonary toxicity. In the absence of NQO1, as can occur by genetic mutation, the human airway is protected from harmful effects of ozone. We recently reported that NQO1-null mice are protected from airway hyperresponsiveness and pulmonary inflammation following ozone exposure. Yet, NQO1 regenerates intracellular antioxidants and therefore should protect the individual from oxidative stress. To explain this paradox, we tested whether in the absence of NQO1, ozone exposure results in increased generation of A2-Isoprostane, a cyclopentenone Isoprostane that blunts inflammation. Using GC/MS, we found that NQO1-null mice had greater lung tissue levels of D2- and E2-Isoprostanes, the precursors of J2-, A2-Isoprostanes, both at baseline and following ozone exposure compared to congenic wild-type mice. We confirmed in primary cultures of normal human bronchial epithelial cells, that A2-Isoprostane inhibited ozone-induced NF-kB activation and IL-8 regulation. Furthermore, we determined that A2-Isoprostane covalently modified the active Cys179 domain in Inhibitory kB Kinase in the presence of ozone in vitro, thus establishing the biochemical basis for A2-Isoprostane inhibition of NF-kB. Our results demonstrate that host factors may regulate pulmonary susceptibility to ozone by regulating the generation of A2-Isoprostanes in the lung. These observations provide the biochemical basis for the epidemiologic observation that NQO1 regulates pulmonary susceptibility to ozone.
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nadph quinone oxidoreductase 1 regulates host susceptibility to ozone via Isoprostane generation
Journal of Biological Chemistry, 2013Co-Authors: Apparao B Kummarapurugu, Bernard M Fischer, Shuo Zheng, Ginger L Milne, Andrew J Ghio, Erin N Pottskant, Michael W Foster, Erik J Soderblom, Laura G Dubois, Arthur M MoseleyAbstract:NADPH:quinone oxidoreductase 1 (NQO1) is recognized as a major susceptibility gene for ozone-induced pulmonary toxicity. In the absence of NQO1 as can occur by genetic mutation, the human airway is protected from harmful effects of ozone. We recently reported that NQO1-null mice are protected from airway hyperresponsiveness and pulmonary inflammation following ozone exposure. However, NQO1 regenerates intracellular antioxidants and therefore should protect the individual from oxidative stress. To explain this paradox, we tested whether in the absence of NQO1 ozone exposure results in increased generation of A(2)-Isoprostane, a cyclopentenone Isoprostane that blunts inflammation. Using GC-MS, we found that NQO1-null mice had greater lung tissue levels of D(2)- and E(2)-Isoprostanes, the precursors of J(2)- and A(2)-Isoprostanes, both at base line and following ozone exposure compared with congenic wild-type mice. We confirmed in primary cultures of normal human bronchial epithelial cells that A(2)-Isoprostane inhibited ozone-induced NF-κB activation and IL-8 regulation. Furthermore, we determined that A(2)-Isoprostane covalently modified the active Cys(179) domain in inhibitory κB kinase in the presence of ozone in vitro, thus establishing the biochemical basis for A(2)-Isoprostane inhibition of NF-κB. Our results demonstrate that host factors may regulate pulmonary susceptibility to ozone by regulating the generation of A(2)-Isoprostanes in the lung. These observations provide the biochemical basis for the epidemiologic observation that NQO1 regulates pulmonary susceptibility to ozone.
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Isoprostanes and asthma.
Biochimica et biophysica acta, 2011Co-Authors: Judith A. Voynow, Apparao B KummarapuruguAbstract:Isoprostanes are prostaglandin (PG)-like compounds generated in vivo following oxidative stress by non-enzymatic peroxidation of polyunsaturated fatty acids, including arachidonic acid. They are named based on their prostane ring structure and by the localization of hydroxyl groups on the carbon side chain; these structural differences result in a broad array of Isoprostane molecules with varying biological properties. Generation of specific Isoprostanes is also regulated by host cell redox conditions; reducing conditions favor F₂-Isoprostane production while under conditions with deficient antioxidant capacity, D₂- and E₂-Isoprostanes are formed. F₂-Isoprostanes (F₂-isoP) are considered reliable markers of oxidative stress in pulmonary diseases including asthma. Importantly, F₂-isoP and other Isoprostanes function as ligands for PG receptors, and potentially other receptors that have not yet been identified. They have been reported to have important biological properties in many organs. In the lung, Isoprostanes regulate cellular processes affecting airway smooth muscle tone, neural secretion, epithelial ion flux, endothelial cell adhesion and permeability, and macrophage adhesion and function. In this review, we will summarize the evidence that F₂-isoP functions as a marker of oxidative stress in asthma, and that F₂-isoP and other Isoprostanes exert biological effects that contribute to the pathogenesis of asthma. This article is part of a Special Issue entitled Biochemistry of Asthma.
Arthur M Moseley - One of the best experts on this subject based on the ideXlab platform.
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nadph quinone oxidoreductase 1 regulates host susceptibility to ozone via Isoprostane generation
Journal of Biological Chemistry, 2013Co-Authors: Apparao B Kummarapurugu, Bernard M Fischer, Shuo Zheng, Ginger L Milne, Andrew J Ghio, Erin N Pottskant, Michael W Foster, Erik J Soderblom, Laura G Dubois, Arthur M MoseleyAbstract:Abstract NADPH quinone oxidoreductase 1 (NQO1) is recognized as a major susceptibility gene for ozone-induced pulmonary toxicity. In the absence of NQO1, as can occur by genetic mutation, the human airway is protected from harmful effects of ozone. We recently reported that NQO1-null mice are protected from airway hyperresponsiveness and pulmonary inflammation following ozone exposure. Yet, NQO1 regenerates intracellular antioxidants and therefore should protect the individual from oxidative stress. To explain this paradox, we tested whether in the absence of NQO1, ozone exposure results in increased generation of A2-Isoprostane, a cyclopentenone Isoprostane that blunts inflammation. Using GC/MS, we found that NQO1-null mice had greater lung tissue levels of D2- and E2-Isoprostanes, the precursors of J2-, A2-Isoprostanes, both at baseline and following ozone exposure compared to congenic wild-type mice. We confirmed in primary cultures of normal human bronchial epithelial cells, that A2-Isoprostane inhibited ozone-induced NF-kB activation and IL-8 regulation. Furthermore, we determined that A2-Isoprostane covalently modified the active Cys179 domain in Inhibitory kB Kinase in the presence of ozone in vitro, thus establishing the biochemical basis for A2-Isoprostane inhibition of NF-kB. Our results demonstrate that host factors may regulate pulmonary susceptibility to ozone by regulating the generation of A2-Isoprostanes in the lung. These observations provide the biochemical basis for the epidemiologic observation that NQO1 regulates pulmonary susceptibility to ozone.
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nadph quinone oxidoreductase 1 regulates host susceptibility to ozone via Isoprostane generation
Journal of Biological Chemistry, 2013Co-Authors: Apparao B Kummarapurugu, Bernard M Fischer, Shuo Zheng, Ginger L Milne, Andrew J Ghio, Erin N Pottskant, Michael W Foster, Erik J Soderblom, Laura G Dubois, Arthur M MoseleyAbstract:NADPH:quinone oxidoreductase 1 (NQO1) is recognized as a major susceptibility gene for ozone-induced pulmonary toxicity. In the absence of NQO1 as can occur by genetic mutation, the human airway is protected from harmful effects of ozone. We recently reported that NQO1-null mice are protected from airway hyperresponsiveness and pulmonary inflammation following ozone exposure. However, NQO1 regenerates intracellular antioxidants and therefore should protect the individual from oxidative stress. To explain this paradox, we tested whether in the absence of NQO1 ozone exposure results in increased generation of A(2)-Isoprostane, a cyclopentenone Isoprostane that blunts inflammation. Using GC-MS, we found that NQO1-null mice had greater lung tissue levels of D(2)- and E(2)-Isoprostanes, the precursors of J(2)- and A(2)-Isoprostanes, both at base line and following ozone exposure compared with congenic wild-type mice. We confirmed in primary cultures of normal human bronchial epithelial cells that A(2)-Isoprostane inhibited ozone-induced NF-κB activation and IL-8 regulation. Furthermore, we determined that A(2)-Isoprostane covalently modified the active Cys(179) domain in inhibitory κB kinase in the presence of ozone in vitro, thus establishing the biochemical basis for A(2)-Isoprostane inhibition of NF-κB. Our results demonstrate that host factors may regulate pulmonary susceptibility to ozone by regulating the generation of A(2)-Isoprostanes in the lung. These observations provide the biochemical basis for the epidemiologic observation that NQO1 regulates pulmonary susceptibility to ozone.
Jelena Klawitter - One of the best experts on this subject based on the ideXlab platform.
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Quantification of 15‐F2t‐Isoprostane in human plasma and urine: results from enzyme‐linked immunoassay and liquid chromatography/tandem mass spectrometry cannot be compared
Rapid Communications in Mass Spectrometry, 2011Co-Authors: Jelena Klawitter, Manuel Haschke, Touraj Shokati, Uwe ChristiansAbstract:Quantification of F(2)-Isoprostanes is considered a reliable index of the oxidative stress status in vivo. Several immunoassays and chromatography/mass spectrometry-based assays are available for 15-F(2t)-Isoprostane quantification. However, it remains unclear if results of immunoassays using different assays can be compared with those of liquid chromatography/mass spectrometry (LC/MS) assays. Previous studies comparing enzyme-linked immunosorbent assay (ELISA) and more specific gas chromatography/mass spectrometry assays have already indicated that ELISAs may overestimate 15-F(2t)-Isoprostane concentrations in human plasma. Concentrations of 15-F(2t)-Isoprostane in 25 human plasma and urine samples were measured by three commercially available ELISA assays (Assay Designs, Cayman Chemical and Oxford Biomedical Research) and compared with the concentrations measured with a validated, semi-automated high-throughput HPLC tandem mass spectrometry assay (LC/LC-MS/MS). All three ELISAs measured substantially higher 15-F(2t)-Isoprostane concentrations (2.1-182.2-fold higher in plasma; 0.4-61.9-fold higher in urine) than LC/LC-MS/MS. Utilization of solid-phase extraction (SPE) columns, especially Isoprostane affinity purification columns, brought ELISA Isoprostane urine concentrations closer to the LC/LC-MS/MS results. However, SPE did not have much of an effect on ELISA plasma concentrations which remained significantly higher than corresponding LC/LC-MS/MS results. A poor correlation not only between LC/LC-MS/MS and immunoassay results, but also among the immunoassays was found. Especially in plasma, ELISAs grossly overestimate 15-F(2t)-Isoprostane concentrations and are not comparable with each other or with LC/LC-MS/MS. It is most disturbing that a sample with relatively high concentrations measured with one ELISA may show low concentrations with another ELISA, and vice versa, potentially affecting the conclusions drawn from such data. The use of specific mass spectrometry-based assays seems advisable.
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quantification of 15 f2t Isoprostane in human plasma and urine results from enzyme linked immunoassay and liquid chromatography tandem mass spectrometry cannot be compared
Rapid Communications in Mass Spectrometry, 2011Co-Authors: Jelena Klawitter, Manuel Haschke, Touraj Shokati, Uwe ChristiansAbstract:Quantification of F(2)-Isoprostanes is considered a reliable index of the oxidative stress status in vivo. Several immunoassays and chromatography/mass spectrometry-based assays are available for 15-F(2t)-Isoprostane quantification. However, it remains unclear if results of immunoassays using different assays can be compared with those of liquid chromatography/mass spectrometry (LC/MS) assays. Previous studies comparing enzyme-linked immunosorbent assay (ELISA) and more specific gas chromatography/mass spectrometry assays have already indicated that ELISAs may overestimate 15-F(2t)-Isoprostane concentrations in human plasma. Concentrations of 15-F(2t)-Isoprostane in 25 human plasma and urine samples were measured by three commercially available ELISA assays (Assay Designs, Cayman Chemical and Oxford Biomedical Research) and compared with the concentrations measured with a validated, semi-automated high-throughput HPLC tandem mass spectrometry assay (LC/LC-MS/MS). All three ELISAs measured substantially higher 15-F(2t)-Isoprostane concentrations (2.1-182.2-fold higher in plasma; 0.4-61.9-fold higher in urine) than LC/LC-MS/MS. Utilization of solid-phase extraction (SPE) columns, especially Isoprostane affinity purification columns, brought ELISA Isoprostane urine concentrations closer to the LC/LC-MS/MS results. However, SPE did not have much of an effect on ELISA plasma concentrations which remained significantly higher than corresponding LC/LC-MS/MS results. A poor correlation not only between LC/LC-MS/MS and immunoassay results, but also among the immunoassays was found. Especially in plasma, ELISAs grossly overestimate 15-F(2t)-Isoprostane concentrations and are not comparable with each other or with LC/LC-MS/MS. It is most disturbing that a sample with relatively high concentrations measured with one ELISA may show low concentrations with another ELISA, and vice versa, potentially affecting the conclusions drawn from such data. The use of specific mass spectrometry-based assays seems advisable.
Ginger L Milne - One of the best experts on this subject based on the ideXlab platform.
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nadph quinone oxidoreductase 1 regulates host susceptibility to ozone via Isoprostane generation
Journal of Biological Chemistry, 2013Co-Authors: Apparao B Kummarapurugu, Bernard M Fischer, Shuo Zheng, Ginger L Milne, Andrew J Ghio, Erin N Pottskant, Michael W Foster, Erik J Soderblom, Laura G Dubois, Arthur M MoseleyAbstract:Abstract NADPH quinone oxidoreductase 1 (NQO1) is recognized as a major susceptibility gene for ozone-induced pulmonary toxicity. In the absence of NQO1, as can occur by genetic mutation, the human airway is protected from harmful effects of ozone. We recently reported that NQO1-null mice are protected from airway hyperresponsiveness and pulmonary inflammation following ozone exposure. Yet, NQO1 regenerates intracellular antioxidants and therefore should protect the individual from oxidative stress. To explain this paradox, we tested whether in the absence of NQO1, ozone exposure results in increased generation of A2-Isoprostane, a cyclopentenone Isoprostane that blunts inflammation. Using GC/MS, we found that NQO1-null mice had greater lung tissue levels of D2- and E2-Isoprostanes, the precursors of J2-, A2-Isoprostanes, both at baseline and following ozone exposure compared to congenic wild-type mice. We confirmed in primary cultures of normal human bronchial epithelial cells, that A2-Isoprostane inhibited ozone-induced NF-kB activation and IL-8 regulation. Furthermore, we determined that A2-Isoprostane covalently modified the active Cys179 domain in Inhibitory kB Kinase in the presence of ozone in vitro, thus establishing the biochemical basis for A2-Isoprostane inhibition of NF-kB. Our results demonstrate that host factors may regulate pulmonary susceptibility to ozone by regulating the generation of A2-Isoprostanes in the lung. These observations provide the biochemical basis for the epidemiologic observation that NQO1 regulates pulmonary susceptibility to ozone.
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nadph quinone oxidoreductase 1 regulates host susceptibility to ozone via Isoprostane generation
Journal of Biological Chemistry, 2013Co-Authors: Apparao B Kummarapurugu, Bernard M Fischer, Shuo Zheng, Ginger L Milne, Andrew J Ghio, Erin N Pottskant, Michael W Foster, Erik J Soderblom, Laura G Dubois, Arthur M MoseleyAbstract:NADPH:quinone oxidoreductase 1 (NQO1) is recognized as a major susceptibility gene for ozone-induced pulmonary toxicity. In the absence of NQO1 as can occur by genetic mutation, the human airway is protected from harmful effects of ozone. We recently reported that NQO1-null mice are protected from airway hyperresponsiveness and pulmonary inflammation following ozone exposure. However, NQO1 regenerates intracellular antioxidants and therefore should protect the individual from oxidative stress. To explain this paradox, we tested whether in the absence of NQO1 ozone exposure results in increased generation of A(2)-Isoprostane, a cyclopentenone Isoprostane that blunts inflammation. Using GC-MS, we found that NQO1-null mice had greater lung tissue levels of D(2)- and E(2)-Isoprostanes, the precursors of J(2)- and A(2)-Isoprostanes, both at base line and following ozone exposure compared with congenic wild-type mice. We confirmed in primary cultures of normal human bronchial epithelial cells that A(2)-Isoprostane inhibited ozone-induced NF-κB activation and IL-8 regulation. Furthermore, we determined that A(2)-Isoprostane covalently modified the active Cys(179) domain in inhibitory κB kinase in the presence of ozone in vitro, thus establishing the biochemical basis for A(2)-Isoprostane inhibition of NF-κB. Our results demonstrate that host factors may regulate pulmonary susceptibility to ozone by regulating the generation of A(2)-Isoprostanes in the lung. These observations provide the biochemical basis for the epidemiologic observation that NQO1 regulates pulmonary susceptibility to ozone.
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oxidative stress measured by urine f2 Isoprostane level is associated with prostate cancer
The Journal of Urology, 2011Co-Authors: Daniel A Barocas, Jackson L Roberts, Jason D Morrow, Ginger L Milne, Saundra Motley, Michael S Cookson, Sam S Chang, David F Penson, Qi Dai, Raoul S ConcepcionAbstract:Purpose: Oxidative stress is implicated in prostate cancer by several lines of evidence. We studied the relationship between the level of F2-Isoprostanes, a validated biomarker of oxidative stress, and prostate cancer and high grade prostatic intraepithelial neoplasia.Materials and Methods: This case-control analysis within the Nashville Men's Health Study included men recruited at prostate biopsy. Body morphometrics, health history and urine were collected from more than 2,000 men before biopsy. F2-Isoprostanes were measured by gas chromatography/mass spectrometry within an age matched sample of Nashville Men's Health Study participants that included 140 patients with high grade prostatic intraepithelial neoplasia, 160 biopsy negative controls and 200 prostate cancer cases. Multivariable linear and logistic regression was used to determine the associations between F2-Isoprostane level, and high grade prostatic intraepithelial neoplasia and prostate cancer.Results: Mean patient age was 66.9 years (SD 7.2)...
