Peter Thorne - Academia.edu (original) (raw)
Papers by Peter Thorne
BMJ Open, 2019
ObjectivesHearing loss is one of the most prevalent conditions affecting older people. In additio... more ObjectivesHearing loss is one of the most prevalent conditions affecting older people. In addition, there is little known about the factors influencing the uptake of hearing services among underserved communities. Our objective was to identify the barriers to accessing hearing care services among older Pacific Island people in New Zealand.SettingsEligible participants from Auckland City, New Zealand.ParticipantsIndividual face-to-face in-depth interviews were conducted with 36 older Pacific Island people who were experienced hearing difficulties.MethodsA Pacific Island research methodology (Talanoa) and the ‘Health Care Access Barriers’ (HCAB) model, which identifies modifiable barriers to healthcare, was used as a theoretical framework for this research. The interviews were transcribed and analysed using a deductive approach to identify HCAB themes and subthemes experienced by older Pacific Island people.ResultsIdentified themes aligned with HCAB’s themes of financial, structural a...
The New Zealand medical journal, Jan 18, 2018
Ear and hearing health services are scarce within Pacific Island countries. Where available, they... more Ear and hearing health services are scarce within Pacific Island countries. Where available, they remain under-resourced, despite there being a high estimated prevalence of otitis media and otitis media-related hearing loss. This study examines the potential for improving ear and hearing health strategies by examining key factors, opportunities and challenges, working with Fiji as a case study. A series of semi-structured interviews were conducted with professionals who had experience in otitis media programme implementation and/or professionals with working experience within the Pacific region and the Fiji health system. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis methods. The three main themes, Identification, Integration, Sustain, highlight the importance of a Pacific-based, locally-driven strategy that builds on existing infrastructure. Three operational themes, Advocacy, Funding and Long-Term Vision, were pivotal to the viability of...
Cochlear Implants International, 2017
To study the changes in behavioural and cortical responses over time in a child with single-sided... more To study the changes in behavioural and cortical responses over time in a child with single-sided deafness fitted with a cochlear implant (CI). Cortical auditory evoked potentials (CAEPs) in noise (+5 dB signal-to-noise ratio) were recorded and auditory skills were assessed using tests of sound localization, spatial speech perception in noise, and self-ratings of auditory abilities (Listening inventory for education, LIFE and Speech, spatial and qualities of hearing questionnaire, SSQ parental version). Measures were obtained prior to and after a CI fitting, including one, six, and 12 months after the CI switch on. Spatial speech recognition improved over time. At 12 months post-CI, word recognition scores were similar to those of normal hearing children. Signal-to-noise ratios for sentences decreased (i.e. improved) over time post-CI. Sound localization markedly improved at 12 months post-CI compared to baseline. Self-perception of difficulty scores decreased over time. Parental ratings of hearing abilities improved compared to baseline for all subscales. There were changes in the P1-N1-P2 complex at 12 months post-CI, which were clearer frontally across stimuli. Further research is needed to understand the significance of such changes after CI fitting for single-sided deafness. Although the changes observed could reflect maturational changes, the clinically significant improvement in recognition of speech in noise and improved questionnaire results suggest that the CI was beneficial, consistent with the feedback from the participant.
International journal of audiology, May 12, 2017
To develop and assess use, acceptability and feasibility of an ecological hearing conservation pr... more To develop and assess use, acceptability and feasibility of an ecological hearing conservation programme for workplaces. A school-based public health hearing preservation education programme (Dangerous Decibels®) was adapted for workplaces using the Multi-level Approach to Community Health (MATCH) Model. The programme was delivered in small manufacturing companies and evaluated using a questionnaire before the training and at one week and two-months after training. Workers (n = 56) from five small manufacturing companies were recruited. There was a significant improvement in knowledge, attitudes and behaviour of workers at the intrapersonal level; in behaviour motivation and safety culture at the interpersonal and organisational levels; and an overall improvement in hearing-health behaviour after two months post-intervention. The developed programme offers a simple, interactive and theory-based intervention that is well accepted and effective in promoting positive hearing-health beh...
Hearing research, Jan 26, 2016
Our previous studies have shown that the stimulation of A1 adenosine receptors in the inner ear c... more Our previous studies have shown that the stimulation of A1 adenosine receptors in the inner ear can mitigate the loss of sensory hair cells and hearing loss caused by exposure to traumatic noise. Here, we focus on the role of adenosine receptors (AR) in the development of noise-induced neural injury in the cochlea using A1AR and A2AAR null mice (A1AR(-/-) and A2AAR(-/-)). Wildtype (WT) and AR deficient mice were exposed to octave band noise (8-16 kHz, 100 dB SPL) for 2 h to induce cochlear injury and hearing loss. Auditory thresholds and input/output functions were assessed using auditory brainstem responses (ABR) before and two weeks post-exposure. The loss of outer hair cells (OHC), afferent synapses and spiral ganglion neurons (SGN) were assessed by quantitative histology. A1AR(-/-) mice (6-8 weeks old) displayed a high frequency hearing loss (ABR threshold shift and reduced ABR wave I and II amplitudes). This hearing loss was further aggravated by acute noise exposure and exceed...
Journal of the Autonomic Nervous System, 2000
On 15 February 2017, the Catalan chemist Antoni Ballester i Nolla left us after a long illness. B... more On 15 February 2017, the Catalan chemist Antoni Ballester i Nolla left us after a long illness. Born in Mont-Roig del Camp in 1920, he moved to Barcelona in the 1930s when his father, a state school teacher, was posted to the capital. A man committed to freedom, Ballester volunteered at the age of 17 to defend the Spanish Republic against fascist aggression. He suffered the shameful refugee camps in the south of France until he was able to return to Barcelona. At the end of the Spanish civil war, he obtained a doctorate in Chemistry and Biological Sciences with an excellent cum laude mark for his doctoral thesis. His fondness for learning and his curiosity about the behaviour of natural phenomena led him to closely observe these processes from a very young age. At the age of 10, he published his first article in a local newspaper in Reus under the title An abnormal July, in which he considered why it was cold in the middle of summer. He married Assumpció, a biologist and had a son, two grandchildren and three great-grandchildren.
Seminars in Neuroscience, 1996
Extracellular purines play multiple roles in a variety of sensory systems acting as neural signal... more Extracellular purines play multiple roles in a variety of sensory systems acting as neural signalling and humoral factors via purinoceptors. For example, ATP and adenosine have a neurosignalling role in autonomic sensory-motor reflexes, mechanoreception and chemoreception mediated via vagus nerve afferents, and in nociception. Purinergic neuromodulation of vision via adenosine in the retina is well established and there is mounting evidence for a neuromodulatory role for ATP in the inner ear. Humoral purinergic actions are found in the eye where adenosine clearly has an important vascular and humoral influence and in the inner ear where ATP probably regulates fluid homeostasis, hearing sensitivity and development. Clearly purinergic signalling underpins the physiology of many of the body's sensory systems.
Journal of the Association for Research in Otolaryngology, 2015
The dorsal cochlear nucleus (DCN) is a major subdivision of the mammalian cochlear nucleus (CN) t... more The dorsal cochlear nucleus (DCN) is a major subdivision of the mammalian cochlear nucleus (CN) that is thought to be involved in sound localization in the vertical plane and in feature extraction of sound stimuli. The main principal cell type (pyramidal cells) integrates auditory and non-auditory inputs, which are considered to be important in performing sound localization tasks. This study aimed to investigate the histological development of the CD-1 mouse DCN, focussing on the postnatal period spanning the onset of hearing (P12). Fluorescent Nissl staining revealed that the three layers of the DCN were identifiable as early as P6 with subsequent expansion of all layers with age. Significant increases in the size of pyramidal and cartwheel cells were observed between birth and P12. Immunohistochemistry showed substantial changes in synaptic distribution during the first two postnatal weeks with subsequent maturation of the presumed mossy fibre terminals. In addition, GFAP immunolabelling identified several glial cell types in the DCN including the observation of putative tanycytes for the first time. Each glial cell type had specific spatial and temporal patterns of maturation with apparent rapid development during the first two postnatal weeks but little change thereafter. The rapid maturation of the structural organization and DCN components prior to the onset of hearing possibly reflects an influence from spontaneous activity originating in the cochlea/auditory nerve. Further refinement of these connections and development of the non-auditory connections may result from the arrival of acoustic input and experience dependent mechanisms.
NeuroReport, 1997
The site of extracellular ATP signalling in the retina was investigated by examining expression o... more The site of extracellular ATP signalling in the retina was investigated by examining expression of the P2X2 receptor (P2X2R) subunit which assembles to form ATP-gated ion channels. Indirect in situ RT-PCR in situ hybridization localized the presence of mRNA for the P2X2R subunit within the soma of photoreceptors, inner nuclear layer neurones and the retina ganglion cells. Use of an antiserum specific for the P2X2R subunit confirmed the expression of the protein by these cells and demonstrated a particularly dense immunolabelling within the inner plexiform layer containing the dendritic processes of the retina ganglion cells. The outer segment of the photoreceptors also exhibited P2X2R-like immunoreactivity. The extensive expression of ATP-gated ion channel protein within the retina suggests that extracellular ATP plays diverse neurohumoral roles in regulation of visual processing and cellular homeostasis.
BioMed Research International, 2015
The international journal of biochemistry & cell biology, 2007
Membrane-bound NTPDase2 is a member of the ecto-nucleoside triphosphate diphosphohydrolase (E-NTP... more Membrane-bound NTPDase2 is a member of the ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) enzyme family involved in the regulation of P2 receptor signaling. NTPDase2 has broad substrate specificity for extracellular nucleotides, but hydrolyses nucleoside 5'-triphosphates with high preference over nucleoside 5'-diphosphates. In this study, we have sought to determine how enzyme substrates acting on P2 receptors affect intracellular NTPDase2 trafficking. To achieve this, Chinese hamster ovary (CHO) cells were transiently transfected with rat-specific NTPDase2 cDNA tagged with green fluorescent protein (GFP), to allow direct visualisation of subcellular localisation and trafficking of NTPDase2. Cells were superfused with NTPDase2 substrates (ATP and UTP) and synthetic nucleotide analogues (ATPgammaS and ADPbetaS), and confocal image stacks were acquired at regular time intervals. NTPDase2 incorporation into the plasma membrane was determined by comparative analysis...
The New Zealand medical journal, Jan 22, 2008
Hearing loss is a major cause of disability in the world. Occupational noise exposure is likely t... more Hearing loss is a major cause of disability in the world. Occupational noise exposure is likely to contribute to a very high proportion of the cases of hearing loss in adults. Concern has been raised by the Accident Compensation Corporation (ACC) in New Zealand about the fact that the number of new cases of noise-induced hearing loss (NIHL) is not declining, despite the health and safety legislation and establishment of hearing conservation programmes in industry. To inform strategies for prevention, a review of the burden of NIHL in New Zealand was undertaken, particularly focusing on the trends in compensation claims and costs, and the associated sociodemographic patterns. A review of the peer-reviewed published literature was conducted to identify national and international estimates of NIHL prevalence. The ACC claims dataset (July 1995 to June 2006) was analysed to describe annual trends in new NIHL claims, cost to ACC, and claimants' age, gender and occupational group. Ther...
Ecto-ATPases, 1997
A number of studies have indicated that adenosine 5′-triphosphate (ATP) acts as a signalling mole... more A number of studies have indicated that adenosine 5′-triphosphate (ATP) acts as a signalling molecule in the cochlea of the inner ear modulating the process of hearing through its interaction with P2 purinoceptors (reviewed by Thorne and Housley1). Determining the terminating mechanism for extracellular ATP in the cochlea thus appears to be highly relevant. The first evidence for ATPase activity in cochlear tissues has been provided by fluorescence imaging of isolated cochlear hair cells2. In that study, binding of the fluorescent ATP analogue 2′-(or -3′)-0-(trinitrophenyl) adenosine 5′-triphosphate (TNP-ATP) to the basolateral region of the hair cells was quenched in the absence of divalent cations, Ca2+ and Mg2+, indicative of ecto-ATPase activity. The present work provides biochemical evidence for ectonucleotidase activity in the cochlea of the guinea-pig. Our in vivo study has demonstrated Ca2+ and Mg2+-dependent hydrolysis of exogenous ATP and production of metabolites in perfused cochlear tissues3. Further in vitro experiments have provided evidence for dephosphorylation of ADP and AMP and measures of ecto-APase, ecto-ADPase and ecto-5′-nucleotidase activity in the cochlear perilymphatic compartment.
BioMed Research International, 2014
We have previously shown that adenosine amine congener (ADAC), a selective A1adenosine receptor a... more We have previously shown that adenosine amine congener (ADAC), a selective A1adenosine receptor agonist, can ameliorate noise- and cisplatin-induced cochlear injury. Here we demonstrate the dose-dependent rescue effects of ADAC on noise-induced cochlear injury in a rat model and establish the time window for treatment.Methods. ADAC (25–300 μg/kg) was administered intraperitoneally to Wistar rats (8–10 weeks old) at intervals (6–72 hours) after exposure to traumatic noise (8–16 kHz, 110 dB sound pressure level, 2 hours). Hearing sensitivity was assessed using auditory brainstem responses (ABR) before and 12 days after noise exposure. Pharmacokinetic studies investigated ADAC concentrations in plasma after systemic (intravenous) administration.Results. ADAC was most effective in the first 24 hours after noise exposure at doses>50 μg/kg, providing up to 21 dB protection (averaged across 8–28 kHz). Pharmacokinetic studies demonstrated a short (5 min) half-life of ADAC in plasma after...
World Journal of Otorhinolaryngology, 2013
ABSTRACT Hearing loss is the most common sensory disability with considerable social and economic... more ABSTRACT Hearing loss is the most common sensory disability with considerable social and economic implications. According to recent World Health Organisation estimates, 360 million people worldwide suffer from moderate to profound hearing loss. Exposure to excessive noise is one of the major causes of sensorineural hearing loss, secondary only to age-related hearing loss (presbyacusis). Since cochlear tissues have limited abilities of repair and regeneration, this damage can be irreversible, leading to cochlear dysfunction and permanent hearing loss. Recent studies have shown that cochlear inflammation can be induced by noise exposure and contribute to the overall pathogenesis of cochlear injury and hearing loss. The cochlea is separated from the systemic circulation by the blood-labyrinth barrier, which is physiologically similar to the blood-brain barrier of the central nervous system. Because of this feature, the cochlea was originally considered an immunologically privileged organ. However, this postulate has been challenged by the evidence of an inflammatory response in the cochlea in the presence of bacterial or viral pathogens or antigens that can cause labyrinthitis. Although the main purpose of the inflammatory reaction is to protect against invading pathogens, the inflammatory response can also cause significant bystander injury to the delicate structures of the cochlea. The cochlear inflammatory response is characterised by the generation of proinflammatory mediators (cytokines, chemokines and adhesion molecules), and the recruitment of inflammatory cells (leukocytes). Here, we present an overview of the current research on cochlear inflammation, with particular emphasis on noise-induced cochlear inflammation. We also discuss treatment strategies aimed at the suppression of inflammation, which may potentially lead to mitigation of hearing loss.
Purinergic Signalling, 2010
Purinergic Signalling, 2010
Hearing loss from noise exposure is a leading occupational disease, with up to 5% of the populati... more Hearing loss from noise exposure is a leading occupational disease, with up to 5% of the population at risk worldwide. Here, we present a novel purine-based pharmacological intervention that can ameliorate noiseinduced cochlear injury. Wistar rats were exposed to narrow-band noise (8-12 kHz, 110 dB SPL, 2-24 h) to induce cochlear damage and permanent hearing loss. The selective adenosine A 1 receptor agonist, adenosine amine congener (ADAC), was administered intraperitoneally (100 µg/kg/day) at time intervals after noise exposure. Hearing thresholds were assessed using auditory brainstem responses and the hair cell loss was evaluated by quantitative histology. Free radical damage in the organ of Corti was assessed using nitrotyrosine immunohistochemistry. The treatment with ADAC after noise exposure led to a significantly greater recovery of hearing thresholds compared with controls. These results were upheld by increased survival of sensory hair cells and reduced nitrotyrosine immunoreactivity in ADAC-treated cochlea. We propose that ADAC could be a valuable treatment for noise-induced cochlear injury in instances of both acute and extended noise exposures.
BMJ Open, 2019
ObjectivesHearing loss is one of the most prevalent conditions affecting older people. In additio... more ObjectivesHearing loss is one of the most prevalent conditions affecting older people. In addition, there is little known about the factors influencing the uptake of hearing services among underserved communities. Our objective was to identify the barriers to accessing hearing care services among older Pacific Island people in New Zealand.SettingsEligible participants from Auckland City, New Zealand.ParticipantsIndividual face-to-face in-depth interviews were conducted with 36 older Pacific Island people who were experienced hearing difficulties.MethodsA Pacific Island research methodology (Talanoa) and the ‘Health Care Access Barriers’ (HCAB) model, which identifies modifiable barriers to healthcare, was used as a theoretical framework for this research. The interviews were transcribed and analysed using a deductive approach to identify HCAB themes and subthemes experienced by older Pacific Island people.ResultsIdentified themes aligned with HCAB’s themes of financial, structural a...
The New Zealand medical journal, Jan 18, 2018
Ear and hearing health services are scarce within Pacific Island countries. Where available, they... more Ear and hearing health services are scarce within Pacific Island countries. Where available, they remain under-resourced, despite there being a high estimated prevalence of otitis media and otitis media-related hearing loss. This study examines the potential for improving ear and hearing health strategies by examining key factors, opportunities and challenges, working with Fiji as a case study. A series of semi-structured interviews were conducted with professionals who had experience in otitis media programme implementation and/or professionals with working experience within the Pacific region and the Fiji health system. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis methods. The three main themes, Identification, Integration, Sustain, highlight the importance of a Pacific-based, locally-driven strategy that builds on existing infrastructure. Three operational themes, Advocacy, Funding and Long-Term Vision, were pivotal to the viability of...
Cochlear Implants International, 2017
To study the changes in behavioural and cortical responses over time in a child with single-sided... more To study the changes in behavioural and cortical responses over time in a child with single-sided deafness fitted with a cochlear implant (CI). Cortical auditory evoked potentials (CAEPs) in noise (+5 dB signal-to-noise ratio) were recorded and auditory skills were assessed using tests of sound localization, spatial speech perception in noise, and self-ratings of auditory abilities (Listening inventory for education, LIFE and Speech, spatial and qualities of hearing questionnaire, SSQ parental version). Measures were obtained prior to and after a CI fitting, including one, six, and 12 months after the CI switch on. Spatial speech recognition improved over time. At 12 months post-CI, word recognition scores were similar to those of normal hearing children. Signal-to-noise ratios for sentences decreased (i.e. improved) over time post-CI. Sound localization markedly improved at 12 months post-CI compared to baseline. Self-perception of difficulty scores decreased over time. Parental ratings of hearing abilities improved compared to baseline for all subscales. There were changes in the P1-N1-P2 complex at 12 months post-CI, which were clearer frontally across stimuli. Further research is needed to understand the significance of such changes after CI fitting for single-sided deafness. Although the changes observed could reflect maturational changes, the clinically significant improvement in recognition of speech in noise and improved questionnaire results suggest that the CI was beneficial, consistent with the feedback from the participant.
International journal of audiology, May 12, 2017
To develop and assess use, acceptability and feasibility of an ecological hearing conservation pr... more To develop and assess use, acceptability and feasibility of an ecological hearing conservation programme for workplaces. A school-based public health hearing preservation education programme (Dangerous Decibels®) was adapted for workplaces using the Multi-level Approach to Community Health (MATCH) Model. The programme was delivered in small manufacturing companies and evaluated using a questionnaire before the training and at one week and two-months after training. Workers (n = 56) from five small manufacturing companies were recruited. There was a significant improvement in knowledge, attitudes and behaviour of workers at the intrapersonal level; in behaviour motivation and safety culture at the interpersonal and organisational levels; and an overall improvement in hearing-health behaviour after two months post-intervention. The developed programme offers a simple, interactive and theory-based intervention that is well accepted and effective in promoting positive hearing-health beh...
Hearing research, Jan 26, 2016
Our previous studies have shown that the stimulation of A1 adenosine receptors in the inner ear c... more Our previous studies have shown that the stimulation of A1 adenosine receptors in the inner ear can mitigate the loss of sensory hair cells and hearing loss caused by exposure to traumatic noise. Here, we focus on the role of adenosine receptors (AR) in the development of noise-induced neural injury in the cochlea using A1AR and A2AAR null mice (A1AR(-/-) and A2AAR(-/-)). Wildtype (WT) and AR deficient mice were exposed to octave band noise (8-16 kHz, 100 dB SPL) for 2 h to induce cochlear injury and hearing loss. Auditory thresholds and input/output functions were assessed using auditory brainstem responses (ABR) before and two weeks post-exposure. The loss of outer hair cells (OHC), afferent synapses and spiral ganglion neurons (SGN) were assessed by quantitative histology. A1AR(-/-) mice (6-8 weeks old) displayed a high frequency hearing loss (ABR threshold shift and reduced ABR wave I and II amplitudes). This hearing loss was further aggravated by acute noise exposure and exceed...
Journal of the Autonomic Nervous System, 2000
On 15 February 2017, the Catalan chemist Antoni Ballester i Nolla left us after a long illness. B... more On 15 February 2017, the Catalan chemist Antoni Ballester i Nolla left us after a long illness. Born in Mont-Roig del Camp in 1920, he moved to Barcelona in the 1930s when his father, a state school teacher, was posted to the capital. A man committed to freedom, Ballester volunteered at the age of 17 to defend the Spanish Republic against fascist aggression. He suffered the shameful refugee camps in the south of France until he was able to return to Barcelona. At the end of the Spanish civil war, he obtained a doctorate in Chemistry and Biological Sciences with an excellent cum laude mark for his doctoral thesis. His fondness for learning and his curiosity about the behaviour of natural phenomena led him to closely observe these processes from a very young age. At the age of 10, he published his first article in a local newspaper in Reus under the title An abnormal July, in which he considered why it was cold in the middle of summer. He married Assumpció, a biologist and had a son, two grandchildren and three great-grandchildren.
Seminars in Neuroscience, 1996
Extracellular purines play multiple roles in a variety of sensory systems acting as neural signal... more Extracellular purines play multiple roles in a variety of sensory systems acting as neural signalling and humoral factors via purinoceptors. For example, ATP and adenosine have a neurosignalling role in autonomic sensory-motor reflexes, mechanoreception and chemoreception mediated via vagus nerve afferents, and in nociception. Purinergic neuromodulation of vision via adenosine in the retina is well established and there is mounting evidence for a neuromodulatory role for ATP in the inner ear. Humoral purinergic actions are found in the eye where adenosine clearly has an important vascular and humoral influence and in the inner ear where ATP probably regulates fluid homeostasis, hearing sensitivity and development. Clearly purinergic signalling underpins the physiology of many of the body's sensory systems.
Journal of the Association for Research in Otolaryngology, 2015
The dorsal cochlear nucleus (DCN) is a major subdivision of the mammalian cochlear nucleus (CN) t... more The dorsal cochlear nucleus (DCN) is a major subdivision of the mammalian cochlear nucleus (CN) that is thought to be involved in sound localization in the vertical plane and in feature extraction of sound stimuli. The main principal cell type (pyramidal cells) integrates auditory and non-auditory inputs, which are considered to be important in performing sound localization tasks. This study aimed to investigate the histological development of the CD-1 mouse DCN, focussing on the postnatal period spanning the onset of hearing (P12). Fluorescent Nissl staining revealed that the three layers of the DCN were identifiable as early as P6 with subsequent expansion of all layers with age. Significant increases in the size of pyramidal and cartwheel cells were observed between birth and P12. Immunohistochemistry showed substantial changes in synaptic distribution during the first two postnatal weeks with subsequent maturation of the presumed mossy fibre terminals. In addition, GFAP immunolabelling identified several glial cell types in the DCN including the observation of putative tanycytes for the first time. Each glial cell type had specific spatial and temporal patterns of maturation with apparent rapid development during the first two postnatal weeks but little change thereafter. The rapid maturation of the structural organization and DCN components prior to the onset of hearing possibly reflects an influence from spontaneous activity originating in the cochlea/auditory nerve. Further refinement of these connections and development of the non-auditory connections may result from the arrival of acoustic input and experience dependent mechanisms.
NeuroReport, 1997
The site of extracellular ATP signalling in the retina was investigated by examining expression o... more The site of extracellular ATP signalling in the retina was investigated by examining expression of the P2X2 receptor (P2X2R) subunit which assembles to form ATP-gated ion channels. Indirect in situ RT-PCR in situ hybridization localized the presence of mRNA for the P2X2R subunit within the soma of photoreceptors, inner nuclear layer neurones and the retina ganglion cells. Use of an antiserum specific for the P2X2R subunit confirmed the expression of the protein by these cells and demonstrated a particularly dense immunolabelling within the inner plexiform layer containing the dendritic processes of the retina ganglion cells. The outer segment of the photoreceptors also exhibited P2X2R-like immunoreactivity. The extensive expression of ATP-gated ion channel protein within the retina suggests that extracellular ATP plays diverse neurohumoral roles in regulation of visual processing and cellular homeostasis.
BioMed Research International, 2015
The international journal of biochemistry & cell biology, 2007
Membrane-bound NTPDase2 is a member of the ecto-nucleoside triphosphate diphosphohydrolase (E-NTP... more Membrane-bound NTPDase2 is a member of the ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) enzyme family involved in the regulation of P2 receptor signaling. NTPDase2 has broad substrate specificity for extracellular nucleotides, but hydrolyses nucleoside 5'-triphosphates with high preference over nucleoside 5'-diphosphates. In this study, we have sought to determine how enzyme substrates acting on P2 receptors affect intracellular NTPDase2 trafficking. To achieve this, Chinese hamster ovary (CHO) cells were transiently transfected with rat-specific NTPDase2 cDNA tagged with green fluorescent protein (GFP), to allow direct visualisation of subcellular localisation and trafficking of NTPDase2. Cells were superfused with NTPDase2 substrates (ATP and UTP) and synthetic nucleotide analogues (ATPgammaS and ADPbetaS), and confocal image stacks were acquired at regular time intervals. NTPDase2 incorporation into the plasma membrane was determined by comparative analysis...
The New Zealand medical journal, Jan 22, 2008
Hearing loss is a major cause of disability in the world. Occupational noise exposure is likely t... more Hearing loss is a major cause of disability in the world. Occupational noise exposure is likely to contribute to a very high proportion of the cases of hearing loss in adults. Concern has been raised by the Accident Compensation Corporation (ACC) in New Zealand about the fact that the number of new cases of noise-induced hearing loss (NIHL) is not declining, despite the health and safety legislation and establishment of hearing conservation programmes in industry. To inform strategies for prevention, a review of the burden of NIHL in New Zealand was undertaken, particularly focusing on the trends in compensation claims and costs, and the associated sociodemographic patterns. A review of the peer-reviewed published literature was conducted to identify national and international estimates of NIHL prevalence. The ACC claims dataset (July 1995 to June 2006) was analysed to describe annual trends in new NIHL claims, cost to ACC, and claimants' age, gender and occupational group. Ther...
Ecto-ATPases, 1997
A number of studies have indicated that adenosine 5′-triphosphate (ATP) acts as a signalling mole... more A number of studies have indicated that adenosine 5′-triphosphate (ATP) acts as a signalling molecule in the cochlea of the inner ear modulating the process of hearing through its interaction with P2 purinoceptors (reviewed by Thorne and Housley1). Determining the terminating mechanism for extracellular ATP in the cochlea thus appears to be highly relevant. The first evidence for ATPase activity in cochlear tissues has been provided by fluorescence imaging of isolated cochlear hair cells2. In that study, binding of the fluorescent ATP analogue 2′-(or -3′)-0-(trinitrophenyl) adenosine 5′-triphosphate (TNP-ATP) to the basolateral region of the hair cells was quenched in the absence of divalent cations, Ca2+ and Mg2+, indicative of ecto-ATPase activity. The present work provides biochemical evidence for ectonucleotidase activity in the cochlea of the guinea-pig. Our in vivo study has demonstrated Ca2+ and Mg2+-dependent hydrolysis of exogenous ATP and production of metabolites in perfused cochlear tissues3. Further in vitro experiments have provided evidence for dephosphorylation of ADP and AMP and measures of ecto-APase, ecto-ADPase and ecto-5′-nucleotidase activity in the cochlear perilymphatic compartment.
BioMed Research International, 2014
We have previously shown that adenosine amine congener (ADAC), a selective A1adenosine receptor a... more We have previously shown that adenosine amine congener (ADAC), a selective A1adenosine receptor agonist, can ameliorate noise- and cisplatin-induced cochlear injury. Here we demonstrate the dose-dependent rescue effects of ADAC on noise-induced cochlear injury in a rat model and establish the time window for treatment.Methods. ADAC (25–300 μg/kg) was administered intraperitoneally to Wistar rats (8–10 weeks old) at intervals (6–72 hours) after exposure to traumatic noise (8–16 kHz, 110 dB sound pressure level, 2 hours). Hearing sensitivity was assessed using auditory brainstem responses (ABR) before and 12 days after noise exposure. Pharmacokinetic studies investigated ADAC concentrations in plasma after systemic (intravenous) administration.Results. ADAC was most effective in the first 24 hours after noise exposure at doses>50 μg/kg, providing up to 21 dB protection (averaged across 8–28 kHz). Pharmacokinetic studies demonstrated a short (5 min) half-life of ADAC in plasma after...
World Journal of Otorhinolaryngology, 2013
ABSTRACT Hearing loss is the most common sensory disability with considerable social and economic... more ABSTRACT Hearing loss is the most common sensory disability with considerable social and economic implications. According to recent World Health Organisation estimates, 360 million people worldwide suffer from moderate to profound hearing loss. Exposure to excessive noise is one of the major causes of sensorineural hearing loss, secondary only to age-related hearing loss (presbyacusis). Since cochlear tissues have limited abilities of repair and regeneration, this damage can be irreversible, leading to cochlear dysfunction and permanent hearing loss. Recent studies have shown that cochlear inflammation can be induced by noise exposure and contribute to the overall pathogenesis of cochlear injury and hearing loss. The cochlea is separated from the systemic circulation by the blood-labyrinth barrier, which is physiologically similar to the blood-brain barrier of the central nervous system. Because of this feature, the cochlea was originally considered an immunologically privileged organ. However, this postulate has been challenged by the evidence of an inflammatory response in the cochlea in the presence of bacterial or viral pathogens or antigens that can cause labyrinthitis. Although the main purpose of the inflammatory reaction is to protect against invading pathogens, the inflammatory response can also cause significant bystander injury to the delicate structures of the cochlea. The cochlear inflammatory response is characterised by the generation of proinflammatory mediators (cytokines, chemokines and adhesion molecules), and the recruitment of inflammatory cells (leukocytes). Here, we present an overview of the current research on cochlear inflammation, with particular emphasis on noise-induced cochlear inflammation. We also discuss treatment strategies aimed at the suppression of inflammation, which may potentially lead to mitigation of hearing loss.
Purinergic Signalling, 2010
Purinergic Signalling, 2010
Hearing loss from noise exposure is a leading occupational disease, with up to 5% of the populati... more Hearing loss from noise exposure is a leading occupational disease, with up to 5% of the population at risk worldwide. Here, we present a novel purine-based pharmacological intervention that can ameliorate noiseinduced cochlear injury. Wistar rats were exposed to narrow-band noise (8-12 kHz, 110 dB SPL, 2-24 h) to induce cochlear damage and permanent hearing loss. The selective adenosine A 1 receptor agonist, adenosine amine congener (ADAC), was administered intraperitoneally (100 µg/kg/day) at time intervals after noise exposure. Hearing thresholds were assessed using auditory brainstem responses and the hair cell loss was evaluated by quantitative histology. Free radical damage in the organ of Corti was assessed using nitrotyrosine immunohistochemistry. The treatment with ADAC after noise exposure led to a significantly greater recovery of hearing thresholds compared with controls. These results were upheld by increased survival of sensory hair cells and reduced nitrotyrosine immunoreactivity in ADAC-treated cochlea. We propose that ADAC could be a valuable treatment for noise-induced cochlear injury in instances of both acute and extended noise exposures.