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Exploring the Acute Effects of Glucocorticoids on Rabbit Vocal Fold Tissue

Gartling, Gary J (2021) Exploring the Acute Effects of Glucocorticoids on Rabbit Vocal Fold Tissue. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Glucocorticoids (GCs) are frequently used to treat vocal fold (VF) inflammation due to their potent anti-inflammatory effects. Glucocorticoids have varying pharmacodynamic properties with effects ranging from reduced angiogenesis, changes in epithelial/endothelial barrier integrity, reduced therapeutic effect after long-term use, and skeletal muscle atrophy. Despite the known diversity of drug activity and associated negative effects, otolaryngologists typically rely on subjective clinical judgments when prescribing GCs, rather than objective evidence of differential efficacy. Elucidating GC-induced VF tissue changes and delineating effects between GCs is necessary for physicians to accurately modify drug selection for patient-specific needs. To inform these knowledge gaps, in-vivo animal models are frequently used due to the ability to study experimentally induced tissue changes that would be impossible to conduct in humans. However, knowledge of the existence and localization of key VF constituents involved in the regulation of VF homeostasis in rabbits - a commonly used model in this field - has not yet been investigated.
The purpose of this study was to: 1) Compare the localization of integral membrane proteins involved in the regulation of VF tissue homeostasis between human and rabbit VF tissue. 2) Investigate the acute effects of intramuscular injections of dexamethasone and methylprednisolone on VF tight junctions, vascularity, therapeutic efficacy, and thyroarytenoid (TA) muscle morphology in rabbit VFs. 3) Investigate the effects of an intracordal injection of dexamethasone on atrophy-associated gene expression and TA muscle morphology in rabbit VFs.
The results of these experiments revealed: 1) Similar localization of key ion transport channels and cell adhesion proteins between rabbit and human VFs. 2) Increases in VF epithelial and endothelial tight junction expression in rabbits treated with 6-daily intramuscular injections of dexamethasone and decreases in global body mass in rabbits treated with methylprednisolone. 3) No evidence of GC-induced atrophy in the VFs of rabbits receiving an intracordal injection of dexamethasone. These findings provide support for the use of rabbits as an experimental model when studying key VF constituents, and evidence of differential effects of GCs at a systemic and VF level. These findings identify an important role for tailored GC selection dependent on patient-specific needs when treating voice disorders.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Gartling, Gary Jgjg20@pitt.eduGjg20
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairRousseau, Bernardrousseau.csd@pitt.edubzr9
Committee MemberHelou, Leahlbh7@pitt.edulbh7
Committee MemberCoyle, James Ljcoyle@pitt.eduJCOYLE
Committee MemberBrad, Nindlbnindl@pitt.edu
Committee MemberBranski, Ryanryan.branski@nyulangone.org
Date: 19 November 2021
Defense Date: 13 October 2021
Approval Date: 24 January 2022
Submission Date: 19 November 2021
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 118
Institution: University of Pittsburgh
Schools and Programs: School of Health and Rehabilitation Sciences > Communication Science and Disorders
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Voice; Steroids; Vocal Fold; Atrophy
Date Deposited: 24 Jan 2022 13:12
Last Modified: 24 Jan 2022 13:12
URI: http://d-scholarship.pitt.edu/id/eprint/41963

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