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  1. Article ; Online: The Interaction of Vitamin D and Corticosteroids

    Jimmy T. Efird / Ethan J. Anderson / Charulata Jindal / Thomas S. Redding / Andrew D. Thompson / Ashlyn M. Press / Julie Upchurch / Christina D. Williams / Yuk Ming Choi / Ayako Suzuki

    International Journal of Environmental Research and Public Health, Vol 19, Iss 447, p

    A Mortality Analysis of 26,508 Veterans Who Tested Positive for SARS-CoV-2

    2022  Volume 447

    Abstract: This data-based cohort consisted of 26,508 (7%) United States veterans out of the 399,290 who tested positive for SARS-CoV-2 from 1 March to 10 September 2020. We aimed to assess the interaction of post-index vitamin D (Vit D) and corticosteroid (CRT) ... ...

    Abstract This data-based cohort consisted of 26,508 (7%) United States veterans out of the 399,290 who tested positive for SARS-CoV-2 from 1 March to 10 September 2020. We aimed to assess the interaction of post-index vitamin D (Vit D) and corticosteroid (CRT) use on 30-day mortality among hospitalized and non-hospitalized patients with coronavirus disease 2019 (COVID-19). Combination Vit D and CRT drug use was assessed according to four multinomial pairs (−|+, −|−, +|+, +|−). Respective categorical effects were computed on a log-binomial scale as adjusted relative risk (aRR). Approximately 6% of veterans who tested positive for SARS-CoV-2 died within 30 days of their index date. Among hospitalized patients, a significantly decreased aRR was observed for the use of Vit D in the absence of CRTs relative to patients who received CRTs but not Vit D (aRR = 0.30; multiplicity corrected, p = 0.0004). Among patients receiving systemically administered CRTs (e.g., dexamethasone), the use of Vit D was associated with fewer deaths in hospitalized patients (aRR = 0.51) compared with non-hospitalized patients (aRR = 2.5) ( P -for-Interaction = 0.0071). Evaluating the effect of modification of these compounds in the context of hospitalization may aid in the management of COVID-19 and provide a better understanding of the pathophysiological mechanisms underlying this and future infectious disease outbreaks.
    Keywords anti-inflammatory ; corticosteroids ; COVID-19 ; cytokine storm ; SARS-CoV-2 ; vitamin D ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2022-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Lipid hydroperoxides promote sarcopenia through carbonyl stress

    Hiroaki Eshima / Justin L Shahtout / Piyarat Siripoksup / MacKenzie J Pearson / Ziad S Mahmassani / Patrick J Ferrara / Alexis W Lyons / John Alan Maschek / Alek D Peterlin / Anthony RP Verkerke / Jordan M Johnson / Anahy Salcedo / Jonathan J Petrocelli / Edwin R Miranda / Ethan J Anderson / Sihem Boudina / Qitao Ran / James E Cox / Micah J Drummond /
    Katsuhiko Funai

    eLife, Vol

    2023  Volume 12

    Abstract: Reactive oxygen species (ROS) accumulation is a cardinal feature of skeletal muscle atrophy. ROS refers to a collection of radical molecules whose cellular signals are vast, and it is unclear which downstream consequences of ROS are responsible for the ... ...

    Abstract Reactive oxygen species (ROS) accumulation is a cardinal feature of skeletal muscle atrophy. ROS refers to a collection of radical molecules whose cellular signals are vast, and it is unclear which downstream consequences of ROS are responsible for the loss of muscle mass and strength. Here, we show that lipid hydroperoxides (LOOH) are increased with age and disuse, and the accumulation of LOOH by deletion of glutathione peroxidase 4 (GPx4) is sufficient to augment muscle atrophy. LOOH promoted atrophy in a lysosomal-dependent, proteasomal-independent manner. In young and old mice, genetic and pharmacological neutralization of LOOH or their secondary reactive lipid aldehydes robustly prevented muscle atrophy and weakness, indicating that LOOH-derived carbonyl stress mediates age- and disuse-induced muscle dysfunction. Our findings provide novel insights for the role of LOOH in sarcopenia including a therapeutic implication by pharmacological suppression.
    Keywords skeletal muscle ; lipid peroxidation ; oxidative stress ; sarcopenia ; muscle atrophy ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Subject code 572
    Language English
    Publishing date 2023-03-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Increased risk of atrial fibrillation among patients undergoing coronary artery bypass graft surgery while receiving nitrates and antiplatelet agents

    Jimmy T. Efird / Charulata Jindal / Andy C. Kiser / Shahab A. Akhter / Patricia B. Crane / Alan P. Kypson / Aaron L. Sverdlov / Stephen W. Davies / Linda C. Kindell / Ethan J. Anderson

    Journal of International Medical Research, Vol

    2018  Volume 46

    Abstract: Background Postoperative atrial fibrillation (POAF) is a frequent complication of coronary artery bypass graft (CABG) surgery. This arrhythmia occurs more frequently among patients who receive perioperative inotropic therapy (PINOT). Administration of ... ...

    Abstract Background Postoperative atrial fibrillation (POAF) is a frequent complication of coronary artery bypass graft (CABG) surgery. This arrhythmia occurs more frequently among patients who receive perioperative inotropic therapy (PINOT). Administration of nitrates with antiplatelet agents reduces the conversion rate of cyclic guanosine monophosphate to guanosine monophosphate. This process is associated with increased concentrations of free radicals, catecholamines, and blood plasma volume. We hypothesized that patients undergoing CABG surgery who receive PINOT may be more susceptible to POAF when nitrates are administered with antiplatelet agents. Methods Clinical records were examined from a prospectively maintained cohort of 4,124 patients undergoing primary isolated CABG surgery to identify POAF-associated factors. Results POAF risk was increased among patients receiving PINOT, and the greatest effect was observed when nitrates were administered with antiplatelet therapy. Adjustment for comorbidities did not substantively change the study results. Conclusions Administration of nitrates with certain antiplatelet agents was associated with an increased POAF risk among patients undergoing CABG surgery. Additional studies are needed to determine whether preventive strategies such as administration of antioxidants will reduce this risk.
    Keywords Medicine (General) ; R5-920
    Subject code 610 ; 616
    Language English
    Publishing date 2018-08-01T00:00:00Z
    Publisher SAGE Publishing
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Potential for Improved Glycemic Control with Dietary Momordica charantia in Patients with Insulin Resistance and Pre-Diabetes

    Jimmy T. Efird / Yuk Ming Choi / Stephen W. Davies / Sanjay Mehra / Ethan J. Anderson / Lalage A. Katunga

    International Journal of Environmental Research and Public Health, Vol 11, Iss 2, Pp 2328-

    2014  Volume 2345

    Abstract: Bitter Melon (Momordica charantia) is a widely used traditional remedy for hyperglycemia. While the medicinal properties of this plant have been studied extensively using in vitro and animal models, the clinical efficacy and safety in humans is largely ... ...

    Abstract Bitter Melon (Momordica charantia) is a widely used traditional remedy for hyperglycemia. While the medicinal properties of this plant have been studied extensively using in vitro and animal models, the clinical efficacy and safety in humans is largely unknown. This review discusses the benefits and limitations of bitter melon supplementation in the context of epidemic levels of insulin resistance and pre-diabetes throughout the world.
    Keywords Momordica charantia ; bitter melon ; insulin resistance ; pre-diabetes ; glycemic control ; Medicine ; R
    Language English
    Publishing date 2014-02-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Corrigendum to “Obesity in a model of gpx4 haploinsufficiency uncovers a causal role for lipid-derived aldehydes in human metabolic disease and cardiomyopathy” [Mol Metab 4 (6) (2015) 493–506]

    Lalage A. Katunga / Preeti Gudimella / Jimmy T. Efird / Scott Abernathy / Taylor A. Mattox / Cherese Beatty / Timothy M. Darden / Kathleen A. Thayne / Hazaim Alwair / Alan P. Kypson / Jitka A. Virag / Ethan J. Anderson

    Molecular Metabolism, Vol 4, Iss 10, p

    2015  Volume 753

    Keywords Internal medicine ; RC31-1245
    Language English
    Publishing date 2015-10-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Obesity in a model of gpx4 haploinsufficiency uncovers a causal role for lipid-derived aldehydes in human metabolic disease and cardiomyopathy

    Lalage A. Katunga / Preeti Gudimella / Jimmy T. Efird / Scott Abernathy / Taylor A. Mattox / Cherese Beatty / Timothy M. Darden / Kathleen A. Thayne / Hazaim Alwair / Alan P. Kypson / Jitka A. Virag / Ethan J. Anderson

    Molecular Metabolism, Vol 4, Iss 6, Pp 493-

    2015  Volume 506

    Abstract: Objective: Lipid peroxides and their reactive aldehyde derivatives (LPPs) have been linked to obesity-related pathologies, but whether they have a causal role has remained unclear. Glutathione peroxidase 4 (GPx4) is a selenoenzyme that selectively ... ...

    Abstract Objective: Lipid peroxides and their reactive aldehyde derivatives (LPPs) have been linked to obesity-related pathologies, but whether they have a causal role has remained unclear. Glutathione peroxidase 4 (GPx4) is a selenoenzyme that selectively neutralizes lipid hydroperoxides, and human gpx4 gene variants have been associated with obesity and cardiovascular disease in epidemiological studies. This study tested the hypothesis that LPPs underlie cardio-metabolic derangements in obesity using a high fat, high sucrose (HFHS) diet in gpx4 haploinsufficient mice (GPx4+/−) and in samples of human myocardium. Methods: Wild-type (WT) and GPx4+/− mice were fed either a standard chow (CNTL) or HFHS diet for 24 weeks, with metabolic and cardiovascular parameters measured throughout. Biochemical and immuno-histological analysis was performed in heart and liver at termination of study, and mitochondrial function was analyzed in heart. Biochemical analysis was also performed on samples of human atrial myocardium from a cohort of 103 patients undergoing elective heart surgery. Results: Following HFHS diet, WT mice displayed moderate increases in 4-hydroxynonenal (HNE)-adducts and carbonyl stress, and a 1.5-fold increase in GPx4 enzyme in both liver and heart, while gpx4 haploinsufficient (GPx4+/−) mice had marked carbonyl stress in these organs accompanied by exacerbated glucose intolerance, dyslipidemia, and liver steatosis. Although normotensive, cardiac hypertrophy was evident with obesity, and cardiac fibrosis more pronounced in obese GPx4+/− mice. Mitochondrial dysfunction manifesting as decreased fat oxidation capacity and increased reactive oxygen species was also present in obese GPx4+/− but not WT hearts, along with up-regulation of pro-inflammatory and pro-fibrotic genes. Patients with diabetes and hyperglycemia exhibited significantly less GPx4 enzyme and greater HNE-adducts in their hearts, compared with age-matched non-diabetic patients. Conclusion: These findings suggest LPPs are key factors underlying ...
    Keywords Glutathione peroxidase 4 ; Lipid peroxidation ; Obesity ; Mitochondria ; Inflammation ; Human heart ; Internal medicine ; RC31-1245
    Subject code 610
    Language English
    Publishing date 2015-06-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Increased Long-Term Mortality among Black CABG Patients Receiving Preoperative Inotropic Agents

    Jimmy T. Efird / William F. Griffin / Daniel F. Sarpong / Stephen W. Davies / Iulia Vann / Nathaniel T. Koutlas / Ethan J. Anderson / Patricia B. Crane / Hope Landrine / Linda Kindell / Zahra J. Iqbal / T. Bruce Ferguson / W. Randolph Chitwood / Alan P. Kypson

    International Journal of Environmental Research and Public Health, Vol 12, Iss 7, Pp 7478-

    2015  Volume 7490

    Abstract: The aim of this study was to examine racial differences in long-term mortality after coronary artery bypass grafting (CABG), stratified by preoperative use of inotropic agents. Black and white patients who required preoperative inotropic support prior to ...

    Abstract The aim of this study was to examine racial differences in long-term mortality after coronary artery bypass grafting (CABG), stratified by preoperative use of inotropic agents. Black and white patients who required preoperative inotropic support prior to undergoing CABG procedures between 1992 and 2011 were compared. Mortality probabilities were computed using the Kaplan-Meier product-limit method. Hazard ratios (HR) and 95% confidence intervals (CI) were computed using a Cox regression model. A total of 15,765 patients underwent CABG, of whom 211 received preoperative inotropic agents within 48 hours of surgery. Long-term mortality differed by race (black versus white) among preoperative inotropic category (inotropes: adjusted HR = 1.6, 95% CI = 1.009–2.4; no inotropes: adjusted HR = 1.15, 95% CI = 1.08–1.2; Pinteraction < 0.0001). Our study identified an independent preoperative risk-factor for long-term mortality among blacks receiving CABG. This outcome provides information that may be useful for surgeons, primary care providers, and their patients.
    Keywords inotropes ; cardiac surgery ; mortality ; disparities ; heart disease ; heart failure ; Medicine ; R
    Language English
    Publishing date 2015-07-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Metformin Improves Insulin Signaling in Obese Rats via Reduced IKKβ Action in a Fiber-Type Specific Manner

    Benjamin T. Bikman / Donghai Zheng / Daniel A. Kane / Ethan J. Anderson / Tracey L. Woodlief / Jesse W. Price / G. Lynis Dohm / P. Darrell Neufer / Ronald N. Cortright

    Journal of Obesity, Vol

    2010  Volume 2010

    Abstract: Metformin is a widely used insulin-sensitizing drug, though its mechanisms are not fully understood. Metformin has been shown to activate AMPK in skeletal muscle; however, its effects on the inhibitor of κB kinaseβ (IKKβ) in this same tissue are unknown. ...

    Abstract Metformin is a widely used insulin-sensitizing drug, though its mechanisms are not fully understood. Metformin has been shown to activate AMPK in skeletal muscle; however, its effects on the inhibitor of κB kinaseβ (IKKβ) in this same tissue are unknown. The aim of this study was to (1) determine the ability of metformin to attenuate IKKβ action, (2) determine whether changes in AMPK activity are associated with changes in IKKβ action in skeletal muscle, and (3) examine whether changes in AMPK and IKKβ function are consistent with improved insulin signaling. Lean and obese male Zuckers received either vehicle or metformin by oral gavage daily for four weeks (four groups of eight). Proteins were measured in white gastrocnemius (WG), red gastrocnemius (RG), and soleus. AMPK phosphorylation increased (P<.05) in WG in both lean (57%) and obese (106%), and this was supported by an increase in phospho-ACC in WG. Further, metformin increased IκBα levels in both WG (150%) and RG (67%) of obese rats, indicative of reduced IKKβ activity (P<.05), and was associated with reduced IRS1-pSer307 (30%) in the WG of obese rats (P<.02). From these data we conclude that metformin treatment appears to exert an inhibitory influence on skeletal muscle IKKβ activity, as evidenced by elevated IκBα levels and reduced IRS1-Ser307 phosphorylation in a fiber-type specific manner.
    Keywords Internal medicine ; RC31-1245
    Subject code 610
    Language English
    Publishing date 2010-01-01T00:00:00Z
    Publisher Hindawi Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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