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17. The Selective 5-HT1A Agonist SR57746A Protects Intestinal Epithelial Cells and Enteric Glia Cells and Promotes Mucosal Recovery in Experimental Colitis

Author

Walldorf, Jens, primary, Porzner, Marc, additional, Neumann, Martin, additional, Joodi, Golsa, additional, Niess, Jan Hendrik, additional, von Boyen, Georg, additional, Mäder, Karsten, additional, Weissbach, Julia, additional, Kleger, Alexander, additional, and Seufferlein, Thomas, additional

Published
2021
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39. Contributors

Author

Patterson, Cam, Rossi, Joseph S., Runge, Marschall S., Stouffer, George A., Abu-el-Haija, Basil, Aiken, Tiffanie, Arora, Sameer, Baker, Matthew S., Baggett, Charles, Bashore, Thomas M., Ben-Or, Sharon, Bensimhon, Hannah, Bode, Christoph, Bode, Michael, Bode, Weeranun D., Boulware, Mark E., Bowdish, Michael E., Brand, Timothy, Brodie, Bruce R., Caldwell, Adam W., Cantey, Eric P., Caranasos, Thomas G., Cascio, Wayne E., Cavender, Matthew A., Chang, Patricia P., Chien, Christopher, Chiles, Christopher D., Chung, Eugene H., Clemmons, David R., Colindres, Romulo E., Conlon, Frank L., Crowner, Jason, Dai, Xuming, Deb, Arjun, Deen, Cody S., Dehmer, Gregory J., Douglas, John S., Jr., Dupont, Allison G., El Sakr, Fredy H., Eron, Joseph J., Farber, Mark A., Ferns, Sunita Juliana, Floris-Moore, Michelle A., Ford, H. James, Foreman, Elizabeth Boger, Frantz, Elman G., Gehi, Anil K., Gettes, Leonard S., Gilbert, Olivia N., Goins, Allie E., Griffith, Anna, Griggs, Thomas R., Haithcock, Benjamin, Handberg, Eileen M., Hinderliter, Alan L., Howell, Lucius, Hummel, James P., Ivester, Thomas S., Jensen, Brian C., Jonas, Beth L., Joodi, Golsa, Katz, Jason N., Khoury, Audrey, Klein, J. Larry, Knowles, Martyn, Lee, David W., Lenihan, Daniel J., Leong, Fong T., Lluri, Gentian, Mendes, Robert, Mendys, Phil, Menon, Venu, Mill, Michael R., Miller, Paula, Mixon, Timothy A., Mounsey, J. Paul, Ohman, E. Magnus, Patel, Rikin, Patterson, Kristine B., Pauley, Eric D., Ro, Pamela S., Romero, Rachel D., Rose-Jones, Lisa J., Schofield, Richard S., Sell-Dottin, Kristen A., Sengupta, Jay D., Shaikh, Faiq, Sheikh, Arif, Sheps, David S., Sheridan, Brett C., Simpson, Ross J., Jr., Slagle, Christopher E., Smith, Sidney C., Jr., Socinski, Mark A., Stewart, Robert D., Stuckey, Thomas D., Sueta, Carla A., Tahir, Khola S., Tan, Walter A., Tate, David A., Traub, Rebecca E., Vaughn, Bradley V., Vavalle, John P., Vinnakota, Anirudh, Voora, Raven A., Weickert, Thelsa Thomas, Wessels, Andy, Wilkins, John T., Willis, Park W., IV, Yang, Eric H., Yeung, Michael, and Zurick, Andrew O., III

Published
2019
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46. Abstract 10316: Association of Metabolic Syndrome With Sudden Death

Author

Sadaf, Murrium I, Mirzaei, Mojtaba, Bogle, Brittany, Hosadurg, Nisha, Joodi, Golsa, and Simpson, Ross J

Abstract

Background:Metabolic syndrome (MetS) comprises physiological, biochemical and clinical factors that increase cardiovascular disease risk. Specific studies examining the risk of MetS associated with sudden death are limited. We assessed the overall prevalence and odds of sudden death by MetS and its components in a population based study.Methods:We adjudicated out-of-hospital sudden deaths by screening all out-of-hospital deaths that were documented by EMS in Wake County, NC (population. 974,289 during 2013 to 2015 aged 18-64 years). We constructed a control group by randomly sampling clinical data of living patients who visited a regional healthcare facility during the same time period. Clinical characteristics and medications up to 2 years prior to sudden death or last clinical encounter of controls were abstracted from clinical records. MetS was presence of at least 3 of 5 components (increased waist circumference (WC), high TG, low HDL-C, high BP, and high fasting glucose) using Adult Treatment Panel III guidelines. Body mass index approximated WC using a published model. We included subjects with data on all MetS components. Logistic regression adjusted for age, sex and ethnicity assessed the odds of sudden death by the number of MetS components. Differences in prevalence was calculated via chi-square.Results:We included 135 cases and 721 controls. Prevalence of MetS was higher among cases than controls (57.8% vs. 38.4%, p<0.001) as were individual components of MetS, except for waist circumference (Figure 1). The odds of sudden death for 3 or more components was 3.5 (95% CI: 1.0-12.5) and for all 5 components was 6.5 (95% CI:1.8-24.4).Conclusion:The odds of sudden death increased by the number of metabolic syndrome components in cases compared with controls. Our findings suggest that metabolic syndrome components exert a collective effect on sudden death. Concurrent targeting of metabolic syndrome and its components may reduce the incidence of sudden death.

Published
2019
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47. Geographic Proximity of Automated External Defibrillators to Out-of-hospital Sudden Deaths in Wake County, North Carolina.

Author

Bogle, Brittany M., Joodi, Golsa, and Simpson, Ross

Abstract

Introduction: Survival rates for out-of-hospital sudden cardiac arrest are substantially improved by access to automated external defibrillators (AEDs) prior to Emergency Medical Services (EMS) arrival. However, AED use may be inhibited if their locations are unknown or far from the bystander. Objectives: We sought to classify out-of-hospital sudden death (OHSD) event locations, ascertain if bystanders utilized AEDs prior to EMS arrival, and calculate the distance to the nearest AED. Methods: From 2013 to 2015, we screened all EMS-reported out-of-hospital deaths aged 18-64 within Wake County, North Carolina to identify OHSDs. We geocoded event locations from EMS records and classified them as residential, commercial, public, or unknown using US Postal Service Residential Delivery Indicator, EMS narratives, and web searches. AED locations and installation dates, registered by law, were obtained from North Carolina Department of Health and Human Services. We used EMS narratives to determine AED use prior to EMS arrival. Walking distance between coordinates of an OHSD location and every AED installed prior to the death date was estimated using the Great-Circle distance. Results: Of 434 adjudicated OHSDs, 390 (90%) were residential, 31 (7%) were commercial, and 11 (2.5%) were public. Of commercial locations, 12 (39%) occurred in hotels. Of public locations, 6(46%) occurred in parking lots or parks. Wake County had 168 registered AEDs during the study period. The mean distance from OHSD to closest AED was 3.2 km (95% CI: 3.0-3.5 km). Only 20 (4.6%) of OHSDs were within 500 meters of an AED; the closest AED was 77 meters from an OHSD. Bystanders used AEDs prior to EMS arrival twice. Conclusions: While potentially lifesaving, AEDs are not placed optimally with respect to OHSD locations and are rarely utilized by bystanders, even in non-residential spaces. Public health strategies should be considered that incentivize optimal AED placement to witnessed cardiac arrest locations. [ABSTRACT FROM AUTHOR]

Published
2017
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49. High-output heart failure due to a giant left circumflex coronary aneurysm with a left atrial fistula and atrial septal defect: a case report.

Author

Lee M, Thomas M, Joodi G, Koppula A, and Soverow J

Abstract

Background: A coronary artery aneurysm is a rare cardiac anomaly that may be incidentally detected on echocardiography. When associated with a coronary cameral fistula, an aneurysm can become symptomatic. We present a unique case of a giant left circumflex coronary aneurysm with a fistula to the left atrium and a large atrial septal defect causing acute heart failure in a young woman during the peripartum period., Case Summary: A 32 year-old woman who presented with hypoxia after the delivery of her fourth child was found to have heart failure with severe mitral regurgitation and multiple abnormal intracardiac shunts. Echocardiography showed a large circular structure with Doppler color flow into the left atrium and between the atria. Cardiac computed tomography showed multiple dilated coronary arteries including a left circumflex coronary artery aneurysm measuring >10 cm in diameter with fistulous communication to the left atrium and a large atrial septal defect. A right heart catheterization was performed, and the patient was diagnosed with high-output heart failure. Surgical closure of the coronary cameral fistula was deferred due to the risk of worsening pressure in the coronary aneurysm, and the patient was referred for cardiac transplantation., Discussion: This case illustrates severe heart failure as a complication of a giant coronary artery aneurysm with fistulization to the left atrium and subsequent shunting through a large atrial defect. Echocardiography allows for the detection of a coronary aneurysm and shunting, and cardiac computed tomography provides detailed visualization of a coronary cameral fistula., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Published
2024
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50. The Selective 5-HT1A Agonist SR57746A Protects Intestinal Epithelial Cells and Enteric Glia Cells and Promotes Mucosal Recovery in Experimental Colitis.

Author

Walldorf J, Porzner M, Neumann M, Joodi G, Niess JH, von Boyen G, Mäder K, Weissbach J, Kleger A, and Seufferlein T

Subjects
Animals, Dextran Sulfate toxicity, Disease Models, Animal, Epithelial Cells metabolism, Humans, Intestinal Mucosa pathology, Mice, Naphthalenes, Neuroglia metabolism, Pyridines, Colitis chemically induced, Colitis drug therapy, Colitis metabolism, Serotonin 5-HT1 Receptor Agonists metabolism
Abstract

Background: Neurotrophic growth factors can stabilize the intestinal barrier by preventing the apoptosis of enteric glial cells (EGCs) and enterocytes. We reasoned that a selective 5-HT1A receptor agonist may have neuroprotective properties in the gut and that topical application of SR57746A might be an effective treatment strategy in inflammatory bowel disease (IBD)., Methods: The therapeutic potential of 5-HT1A receptor agonist SR57746A in IBD was evaluated in vitro (nontransformed NCM460 colonic epithelial cells, SW480 colorectal carcinoma cells) and in vivo (murine dextran sulfate sodium [DSS] colitis and CD4-T-cell transfer colitis). In vitro, we analyzed the effect of SR57746A on apoptosis in intestinal epithelial cells (IECs) and EGCs, and upon proliferation, migration, and intracellular signaling in IECs. In vivo, the effect of topical application of SR57746 on disease activity and on histological and endoscopic findings was compared with intraperitoneal infliximab and placebo, respectively., Results: The SR57746A activates PI3-K/AKT- and ERK-signaling in IECs. Depending on ERK- and AKT activation, SR57746A potently prevents apoptosis of IECs without inducing proliferation or migration in these cells. Moreover, SR57746A prevented apoptosis in EGCs in vitro. Topical SR57746A treatment significantly reduced mucosal injury in 2 experimental murine colitis models and was as effective as intraperitoneal infliximab treatment., Conclusions: Treatment with SR57746A prevents inflammatory cell damage and apoptosis in IECs and EGCs, similar to the neurotrophic effects of EGCs on IECs. Topical treatment with SR57746A could be a candidate for clinical evaluation in the treatment of IBD., (© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Published
2022
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