Cellular Mechanisms In Ototoxicity
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Cellular Mechanisms In Ototoxicity
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Author : Peter S. Steyger
language : en
Publisher: Frontiers Media SA
Release Date : 2018-06-12
Cellular Mechanisms In Ototoxicity written by Peter S. Steyger and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018-06-12 with categories.
The auditory perception of sounds (environmental, vocal or music) is one of the 5 principal senses consciously monitored by our brains, and is crucial for many human endeavors as well as quality of life. Loss of optimal performance in this principal sensory system leads to loss of effective communication and intimacy, as well as increased risk of isolation, depression, cognitive decline, and greater vulnerability to predators. The vestibular system ensures that individuals remain upright and effectively monitor their posture within their spatial surroundings, move effectively, and remain focused on visual targets during motion. The loss of vestibular sensitivity results in postural instability, falls, inability to observe the environment during motion, and a debilitating incapacity to function effectively. The sensory cells for both auditory and vestibular systems are located within the inner ear of the temporal bulla. There are many causes of auditory and vestibular deficits, including congenital (or genetic) events, trauma, aging and loud sound exposures. Ototoxicity refers to damage of the auditory or vestibular structures or functions, as the result of exposure to certain pharmaceuticals, chemicals, and/or ionizing radiation exposure that damage the inner ear. Ototoxicity is a major contributor to acquired hearing loss and vestibular deficits, and is entirely preventable. In 2009, the United States Department of Defense initiated the Hearing Center of Excellence (HCE), headquartered in San Antonio, Texas, in response to the prevalence of acquired auditory and vestibular deficits in military and veteran populations. The knowledge shared in this eBook supports the HCE’s mandate to improve aural protection of military and civilian populations worldwide. The last few years have seen significant advances in understanding the cellular mechanisms underlying ototoxic drug-induced hearing loss and vestibular deficits. In this eBook, we present some of these advances and highlight gaps where further research is needed. Selected articles discuss candidate otoprotective agents that can ameliorate the effects of ototoxicity in the context of how they illustrate cellular mechanisms of ototoxicity. Our goal in illustrating these advances in mechanisms of ototoxicity is to accelerate the development of clinical therapies that prevent or reverse this debilitating disorder.
Cellular Mechanisms Of Ototoxicity
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Author :
language : en
Publisher:
Release Date : 2018
Cellular Mechanisms Of Ototoxicity written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018 with categories.
The auditory perception of sounds (environmental, vocal or music) is one of the 5 principal senses consciously monitored by our brains, and is crucial for many human endeavors as well as quality of life. Loss of optimal performance in this principal sensory system leads to loss of effective communication and intimacy, as well as increased risk of isolation, depression, cognitive decline, and greater vulnerability to predators. The vestibular system ensures that individuals remain upright and effectively monitor their posture within their spatial surroundings, move effectively, and remain focused on visual targets during motion. The loss of vestibular sensitivity results in postural instability, falls, inability to observe the environment during motion, and a debilitating incapacity to function effectively. The sensory cells for both auditory and vestibular systems are located within the inner ear of the temporal bulla. There are many causes of auditory and vestibular deficits, including congenital (or genetic) events, trauma, aging and loud sound exposures. Ototoxicity refers to damage of the auditory or vestibular structures or functions, as the result of exposure to certain pharmaceuticals, chemicals, and/or ionizing radiation exposure that damage the inner ear. Ototoxicity is a major contributor to acquired hearing loss and vestibular deficits, and is entirely preventable. In 2009, the United States Department of Defense initiated the Hearing Center of Excellence (HCE), headquartered in San Antonio, Texas, in response to the prevalence of acquired auditory and vestibular deficits in military and veteran populations. The knowledge shared in this eBook supports the HCE's mandate to improve aural protection of military and civilian populations worldwide. The last few years have seen significant advances in understanding the cellular mechanisms underlying ototoxic drug-induced hearing loss and vestibular deficits. In this eBook, we present some of these advances and highlight gaps where further research is needed. Selected articles discuss candidate otoprotective agents that can ameliorate the effects of ototoxicity in the context of how they illustrate cellular mechanisms of ototoxicity. Our goal in illustrating these advances in mechanisms of ototoxicity is to accelerate the development of clinical therapies that prevent or reverse this debilitating disorder.
Ototoxicity
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Author : Gregg Colon
language : en
Publisher:
Release Date : 2019-08-30
Ototoxicity written by Gregg Colon and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019-08-30 with categories.
This compilation focuses on Ototoxicity, the adverse pharmacological reaction affecting the inner ear or auditory nerve, characterised by cochlear or vestibular dysfunction. Although ototoxic medications play an essential role in modern medicine, they can cause harm and lead to significant morbidity. The authors discuss aminoglycoside antibiotics, loop diuretics, platinum-based chemotherapeutic agents, macrolide antibiotics and antimalarial medications which are among the 600 frequently used ototoxic drugs. Next, an overview of cisplatin-associated ototoxicity, namely its clinical features, incidence rates, molecular and cellular mechanisms and risk factors is provided for health care practitioners managing patients with cancer. Ototoxicity and neurotoxicity are defined from the perspective of chemical agents, nicotine and cotinine, that individuals experience through cigarette smoking and environmental tobacco smoke exposure. Mechanisms for toxicity are described by review of animal and human studies revealing changes in peripheral and central auditory structures after exposure to nicotine. The mechanisms of ototoxicity induced by aminoglycoside are also discussed, as well as the usage of these drugs for treatment of several disorders such as Meniere disease, and possible protective agents. In closing, the authors highlight the serious issue of aminoglycoside mediated hearing loss in cystic fibrosis patients, and also discuss alternative approaches for avoiding aminoglycoside-induced cochleotoxicity.
Inflammatory Mechanisms In Mediating Hearing Loss
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Author : Vickram Ramkumar
language : en
Publisher: Springer
Release Date : 2018-07-18
Inflammatory Mechanisms In Mediating Hearing Loss written by Vickram Ramkumar and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018-07-18 with Medical categories.
Common forms of preventable hearing loss are drug and noise-induced hearing loss which are believed to be produced by a similar mechanism. The generation of reactive oxygen species appears to be a common mechanism mediating hearing loss produced by these different sources. As such, a number of laboratories have focused their research towards identifying the sources of ROS production in the cochlea following administration of chemotherapeutic agents or noise exposure. This led to the identification of ROS generating enzymes, such as xanthine oxidases, nitric oxide synthase, and NADPH oxidases which are activated and/or induced during the development of hearing loss. A consequence of these findings was the implementation of antioxidants in preclinical studies for the treatment of hearing loss. These antioxidants have provided different levels of protection in animal and human studies, but none of these have been approved by the US Food and Drug Administration for the treatment of hearing loss. More recently, it was shown that noise-induced hearing loss was associated with recruitment of inflammatory cells and mediators in the cochlea. This finding would suggest that noise could produce injury to the cochlea which stimulates local and/or circulating inflammatory cells. A similar finding was observed in the cochlea following administration of the anticancer drug, cisplatin. In addition, our laboratory and others have provided a plausible mechanism by which noise or chemotherapeutic agents could stimulate the inflammatory response. Surprisingly, this mechanism involves ROS activation of transcription factors linked to inflammatory processes in the cochlea. These studies have led to the use of anti-inflammatory agents for the treatment of hearing loss. Preliminary studies targeting inflammatory cytokines appear especially promising in preclinical studies. A primary goal of this project is to describe our current understanding of the oxidant hypothesis of noise and drug-induced hearing loss and show how this relates to cochlear inflammation. Several different aspects of the cochlear inflammatory process will be discussed in detail, ranging from the sources of inflammatory cells, chemokines, inflammatory cytokines, and cochlea resident immune cells. Molecular pathways leading to activation of the local inflammatory process will be highlighted and treatment options will be discussed. The relevance of certain clinically used anti-inflammatory interventions, such as trans-typmanic steroids will also be discussed. Furthermore, we will examine recent patents focusing on the use of anti-inflammatory agents for the treatment of drug and noise-induced hearing loss.
Vestibular Damage And Repair In Chronic Ototoxicity
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Author : Erin A. Greguske
language : en
Publisher:
Release Date : 2019
Vestibular Damage And Repair In Chronic Ototoxicity written by Erin A. Greguske and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019 with categories.
"Progressive ototoxicity of the inner ear is prevalent in patients administered aminoglycoside antibiotics with little understanding of how this damage occurs and to what extent it can be recovered. Numerous in vitro and in vivo studies using acute methods have been completed to demonstrate various types of damage in vestibular and auditory tissue, including hair cell damage that results in apoptosis or necrosis, excitotoxic damage, and/or degeneration of their afferents. However, progressive damage has only just recently been studied utilizing a sub-chronic exposure rat model; this model takes into account the progressive exposure mirrored in aminoglycoside administration that is not implied in acute experimentation. With this in mind, the sub-chronic exposure model was adapted for a new mouse model to characterize the progressive damage taking place in vestibular sensory epithelia and ganglia, along with a preliminary characterization in cochlear sensory epithelia. Mice were exposed to 30 mM IDPN (3,3'- iminodipropionitrile) in regular drinking water for 8 weeks, and monitored for vestibular deficits using an established test battery; auditory deficits were recorded using auditory brainstem response (ABR) measurements. Various techniques for identifying functional, histological (scanning/transmission electron microscopy; immunoconfocal), and molecular (mRNA; protein) data were utilized to study alterations in the vestibular and auditory tissues after sub-chronic intoxication. In the vestibular tissue, SEM/TEM imaging demonstrated progressive damage with the loss of calyceal junctions between type I hair cells and their calyx afferents, the fragmentation and retraction of the afferents, stereociliary bundle coalescence, and the unique mechanism of hair cell extrusion, where the cell is ejected from the epithelia into the endolymphatic cavity. Immunoconfocal and qRT-PCR data demonstrated a loss of caspr1 and tenascin-c in the calyceal junctions of type I hair cells and their afferents. A loss of active synapses between hair cells and their afferents was also noted, where active synapses were defined by the pre-synaptic ribeye of the hair cells and the post-synaptic GluA2 receptor of the afferents. Synaptic scaffolding protein expression was upregulated (PSD95, Homer1), which translated into an increase in the protein level (PSD95), likely for hair cell-afferent synapse stabilization and compensation. Progressive damage was noted to be at least partially or completely recoverable up until stereocilia coalescence of the hair cells. Finally, the expression of numerous scaffolding and signaling proteins were shown to be downregulated (qRT-PCR; RNAseq) during the exposure in the vestibular epithelium and ganglion, leading to the hypothesis of a depression in cell-cell adhesion between hair cells and their afferents and a depression in afferent signaling, resulting in an overall depressed system. In the cochlea, profound hearing loss was observed in a tonotopic pattern during the exposure; higher frequencies were affected first with longer exposure times affecting lower frequencies. Outer hair cells were lost tonotopically due to prolonged exposure, followed by active synapse loss of the inner hair cells. Those intoxicated for the first two weeks demonstrated a capacity for recovery before any outer hair cell or active synapse losses were seen. A sub-chronic ototoxic IDPN model demonstrates the progressive damage of the inner ear, allowing for the study of this damage and its potential for recoverability, gaining a clearer understanding of the mechanisms affecting the tissues." -- TDX.
Ototoxicity
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Author : Peter S. Roland
language : en
Publisher: B. C. Decker
Release Date : 2004
Ototoxicity written by Peter S. Roland and has been published by B. C. Decker this book supported file pdf, txt, epub, kindle and other format this book has been release on 2004 with Medical categories.
CD-ROM features complete text and full-color illustrations in searchable PDF files.
Free Radicals In Ent Pathology
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Author : Josef Miller
language : en
Publisher: Humana Press
Release Date : 2015-04-30
Free Radicals In Ent Pathology written by Josef Miller and has been published by Humana Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2015-04-30 with Science categories.
This comprehensive volume examines the current state of free radical biology and its impact on otology, laryngology, and head and neck function. The chapters collectively highlight the interrelationship of basic and translational studies in each area, define the challenges to translation, and identify the existing basic issues that demand investigation as well as the opportunities for novel intervention to prevent and treat ENT pathology and impairment. In each chapter, or in some cases pairs of chapters, the author(s) have included or married issues of basic research with translational challenges and research, thus defining the pathway by which new basic insights may lead to interventions to prevent or treat impairment. The final chapter of this book reflects a meeting of all the contributors, culminating in a discussion and “white paper” that identifies the challenges to the field and defines the studies and collaborations that may lead to improved understanding of free radical biology in ENT and, subsequently, new interventions to medically treat ENT pathology.
Aminoglycoside Ototoxicity
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Author : Stephen A. Lerner
language : en
Publisher: Little, Brown Medical Division
Release Date : 1981
Aminoglycoside Ototoxicity written by Stephen A. Lerner and has been published by Little, Brown Medical Division this book supported file pdf, txt, epub, kindle and other format this book has been release on 1981 with Medical categories.
Defining The Cellular And Molecular Mechanism Of Maternally Inherited Hearing Loss
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Author : Peter John Kullar
language : en
Publisher:
Release Date : 2018
Defining The Cellular And Molecular Mechanism Of Maternally Inherited Hearing Loss written by Peter John Kullar and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018 with categories.
Magnesium In The Central Nervous System
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Author : Robert Vink
language : en
Publisher: University of Adelaide Press
Release Date : 2011
Magnesium In The Central Nervous System written by Robert Vink and has been published by University of Adelaide Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2011 with Medical categories.
The brain is the most complex organ in our body. Indeed, it is perhaps the most complex structure we have ever encountered in nature. Both structurally and functionally, there are many peculiarities that differentiate the brain from all other organs. The brain is our connection to the world around us and by governing nervous system and higher function, any disturbance induces severe neurological and psychiatric disorders that can have a devastating effect on quality of life. Our understanding of the physiology and biochemistry of the brain has improved dramatically in the last two decades. In particular, the critical role of cations, including magnesium, has become evident, even if incompletely understood at a mechanistic level. The exact role and regulation of magnesium, in particular, remains elusive, largely because intracellular levels are so difficult to routinely quantify. Nonetheless, the importance of magnesium to normal central nervous system activity is self-evident given the complicated homeostatic mechanisms that maintain the concentration of this cation within strict limits essential for normal physiology and metabolism. There is also considerable accumulating evidence to suggest alterations to some brain functions in both normal and pathological conditions may be linked to alterations in local magnesium concentration. This book, containing chapters written by some of the foremost experts in the field of magnesium research, brings together the latest in experimental and clinical magnesium research as it relates to the central nervous system. It offers a complete and updated view of magnesiums involvement in central nervous system function and in so doing, brings together two main pillars of contemporary neuroscience research, namely providing an explanation for the molecular mechanisms involved in brain function, and emphasizing the connections between the molecular changes and behavior. It is the untiring efforts of those magnesium researchers who have dedicated their lives to unraveling the mysteries of magnesiums role in biological systems that has inspired the collation of this volume of work.