Myringotomy plays an important role in otological therapy. The procedure requires an efficient anesthesia, which can be obtained without general anesthesia. However, the use of local anesthetics on the tympanic membrane (TM) has been abandoned in many places, as general anesthesia has been readily available. In the present study the effects of some commonly used topical anesthetics on the TM structure and inner ear were tested in an animal model (rat and guinea pig).Four different anesthetic compounds—Xylocaine®, Bonain's liquid, phenol and Emla®—were applied to the TMs of the animals, which were sacrificed 10 minutes to 5 months after application. Morphological effects regarding time after treatment and number of applications were elucidated. At sacrifice the tissue was fixed and the TMs analysed by light microscopy (LM) and transmission electron microscopy (TEM). In nine animals phenol, Xylocaine® Spray or Emla® was applied to the round window niche and ABR recordings were made at 24 h to 6 months after exposure. After the final ABR evaluation the animals were sacrificed and the cochleae prepared for LM and scanning electron microscopy (SEM).On the TM phenol and Bonain's liquid caused instant destruction of the keratinizing stratified squamous epithelium followed by long-lasting hyperplasia of this epithelium and the underlying connective tissue. A pronounced hyperplasia of these two layers was also noted for the Xylocaine® Spray group, but without immediate destruction of the keratinizing epithelium. The extent of structural changes differed in relation to the extent of spreading of the agent. Emla® showed little, if any, sign of epithelial reaction and had no effect on the connective tissue. Regarding the inner ear Emla®, Xylocaine® Spray and phenol induced significantly impaired ABR thresholds mainly affecting the higher frequencies. However, the impaired ABR thresholds were reversible and at the end of the experiment there was no significant impairment compared to the control data. All agents, except Xylocaine®, damaged the hair cells in the basal part of the cochlea as shown by cytocochleogram and SEM analysis.Instant destruction of the epidermis seems to be necessary for an instant anesthetic effect. All agents caused profound connective tissue reactions. The manner of application, depending on the physical properties of the agent, determined the extent of the structural changes. The changes of the connective tissue were concentrated to the submucosal layer, which seems to be the area for reconstruction of the damaged TM. All agents caused functional inner ear changes. With the exception of Xylocaine® they also caused morphological alterations of the cochlea. The functional changes were partly reversible. Topical anesthetics applied to the TM should be used with caution and when used in an appropriate manner they can be considered safe, especially in an inflamed middle ear, with a thickened round window membrane, which should prevent the agents from reaching the inner ear structures. / digitalisering@umu

The aim of this thesis was to elucidate the role of carbonic anhydrase (CA) in the modulation of central pH/CO2-sensitive fictive breathing (measured using in vitro brainstem-spinal cord preparations) in leopard frogs (Rana pipiens) following exposure to chronic hypercapnia (CHC) and chronic hypoxia (CH). CHC caused an augmentation in fictive breathing compared to the controls (normoxic normocapnic). Addition of acetazolamide (ACTZ), a cell-permeant CA inhibitor, to the superfusate reduced fictive breathing in the controls and abolished the CHC-induced augmentation of fictive breathing. ACTZ had no effect on preparations taken from frogs exposed to CH. Addition of bovine CA to the superfusate did not alter fictive breathing in any group, suggesting that the effects of ACTZ were due to inhibition of intracellular CA. Taken together, these results indicate that CA is involved in central pH/CO2 chemoreception and the CHC-induced increase in fictive breathing in the leopard frog.

The aim of this thesis was to elucidate the role of carbonic anhydrase (CA) in the modulation of central pH/CO2-sensitive fictive breathing (measured using in vitro brainstem-spinal cord preparations) in leopard frogs (Rana pipiens) following exposure to chronic hypercapnia (CHC) and chronic hypoxia (CH). CHC caused an augmentation in fictive breathing compared to the controls (normoxic normocapnic). Addition of acetazolamide (ACTZ), a cell-permeant CA inhibitor, to the superfusate reduced fictive breathing in the controls and abolished the CHC-induced augmentation of fictive breathing. ACTZ had no effect on preparations taken from frogs exposed to CH. Addition of bovine CA to the superfusate did not alter fictive breathing in any group, suggesting that the effects of ACTZ were due to inhibition of intracellular CA. Taken together, these results indicate that CA is involved in central pH/CO2 chemoreception and the CHC-induced increase in fictive breathing in the leopard frog.

Intratympanic injection of various otoprotectants through the round window membrane (RWM) might become available in the near future as an alternative to the currently available medical and surgical methods used to treat several inner ear diseases. The most common outcome of such diseases is sensorineural hearing loss (SNHL). Two examples of  these otoprotectants are Edaravone and Brain-Derived Neurotrophic Factor (BDNF), both of which have already proved effective against  noise-induced hair cell loss, barotrauma  and ototoxicity caused by cisplatin. In four different studies we used two electrophysiological methods, auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE), to study the effects of tobramycin and Pseudomonas aeruginosa exotoxin A (PaExoA) on the inner ears of 129 male Sprague-Dawley rats. In two investigations, not only the otoprotective effects of Edaravone on tobramycin-induced ABR threshold shifts and PaExoA-induced DPOAE  threshold changes, were studied but even different application times, in order to establish in which interval it was still possible to achieve effective otoprotection.We found that Edaravone gave otoprotection from tobramycin when injected simultaneously or within 7 days, but it had only a limited effect on the changes in DPOAE thresholds caused by PaExoA when injected 1, 2, or 4 hours after the exotoxin. The effect of BDNF on PaExoA-induced ABR threshold shifts was investigated in two studies, where different doses of intratympanically injected PaExoA were used and where BDNF was applied simultaneously, 12 or 72 hours efter exotoxin instillation. We found that BDNF had an otoprotective effect on SNHL induced by different doses PaExoA when injected simultaneously or with no more than 12 hours delay.

Professional research project (Au.D.)--University of SouthFlorida, 2002. / Title from PDF of title page. / Document formatted into pages; contains 22 pages. / Includes bibliographical references. / Text (Electronic thesis) in PDF format. / ABSTRACT: The purpose of this study was to determine the prevalence of the binaural interaction component (BIC) in a large sample of normal hearing adults, and to measure the absolute latency and amplitude of the BIC as a function of the click rate of the stimulus and the electrode montage. The BIC is obtained by subtracting the auditory evoked potential waveform obtained with binaural stimulation from the waveform obtained by adding the responses from the left and right monaural stimulation. The tested hypothesis was that the recordings of the BIC vary among normal hearing individuals, and BIC latency and amplitude values change as a function of stimulus rate. Studies of the BIC help to explain the neural correlates of some binaural processes, and to develop an electrophysiological index of binaural processes for objective clinical evaluations.Data was completed and analyzed on 47 adults between the ages of 20 and 41 (mean = 25) with hearing in the normal range (thresholds [ 20 dB HL at 500, 1000, 2000, and 4000 Hz in each ear) and no known neurological disorders. The results revealed a great variability in BIC morphology between subjects. The BIC waveforms were categorized into five distinct groups according to the number of positive and negative peaks present. Chi-square analyses revealed a significant relationship between click rate and BIC category; however, the relationship between recording montage and BIC category was insignificant. An Analysis of Variance (ANOVAs) revealed a significant increase in absolute latency and decrease in absolute amplitude of both negative and positive peaks as click rate increased from 7.7/s to 57.7/s. The results did not reveal a significant change in the type of BIC as an effect of electrode montage.In conclusion, the BIC within the binaural difference waveform may be obtained in the majority of young individuals with normal hearing. Specifically, a slower stimulus rate revealed more components of the waveform, as well as an improvement in the morphology of the BIC compared to a faster stimulus rate. As these findings may aid in the development of an electrophysiological index of binaural neural processes in young individuals with normal hearing, more research should be attempted in the study of BIC in other age groups and patients with different audiograms. / System requirements: World Wide Web browser and PDF reader. / Mode of access: World Wide Web.

Bei Anwendung reversibler Betäubungsmethoden erfolgt die Tötung von Schlachttieren durch Blutentzug. Findet dieser nicht oder nicht in ausreichendem Maße statt, besteht die Gefahr, dass die Tiere ihre Wahrnehmungs- und Empfindungsfähigkeit wiedererlangen, bevor sie weiteren Verarbeitungsschritten zugeführt werden. Dies ist aus Tierschutzsicht keinesfalls hinnehmbar und steht im Widerspruch sowohl zum Tierschutzschlachtrecht, als auch zu Verbrauchererwartungen im Hinblick auf einen tierschutzgerechten Schlachtablauf. Es ist deshalb dringend erforderlich den Todeseintritt jedes Einzeltieres zu verifizieren. Dies kann durch direkte Kontrolle der Schlachttiere (klinische Untersuchung, Prüfung der Hirnstammreflexe) nach Eintritt des Todes erfolgen oder bereits frühzeitiger, über eine Erfassung von Parametern, die eine Aussage über die Wahrscheinlichkeit des kurz bevorstehenden Todeseintritts erlauben (TROEGER 2011). Hierfür eignet sich insbesondere die Stichblutmenge, bzw. die Blutflussrate, da ab einer bestimmten Blutmenge pro Zeiteinheit vom kurz bevorstehenden Tod des Tieres ausgegangen werden kann (TROEGER 2010). Zielsetzung dieser Arbeit war zum einen, ein geeignetes Messsystem zur Erfassung des Entbluteverlaufs zu finden und dieses in das Stechkarussell zu integrieren, zum anderen sollte der Zusammenhang zwischen Stichblutmengenanstieg und Todeseintritt der Tiere untersucht werden. In einem ersten Schritt wurden vier verschiedene Messsysteme zur Erfassung des Entbluteverlaufs unter Zuhilfenahme eines Prototyps geprüft: Stichblutwaage (Fa. Bizerba), Füllstandsmesssonde (Fa. Sick), Infrarotkamera „thermoIMAGER TIM“ (Fa. Micro-Epsilon) und Infrarotsensoren „thermoMETER CSmicro“ (Fa. Micro-Epsilon). Als Messparameter und Maß für die Qualität der Entblutung bzw. des Entblutestichs, wurde die Steigung des Blutanstiegs im Blutauffangbehälter verwendet. Das Messsystem „Infrarotsensoren“ erwies sich als am besten geeignetes System und wurde nachfolgend in die Stechkarussellanlage des Partnerschlachthofes integriert und der Messvorgang automatisiert. Um den Zusammenhang zwischen Stichblutmengenanstieg und Todeseintritt der Schweine auf der Nachentblutestrecke zu untersuchen, wurde der Entbluteverlauf in den ersten Sekunden nach dem Stich sowohl mit dem Prototyp (Messsystem Waage) als auch mit dem integrierten IR-Sensor-Messsystem bei einer Stichprobe von 1034 (Prototyp) bzw. 1500 (integriertes System) Schweinen erfasst und anschließend der Eintritt des Hirntodes der Tiere klinisch überprüft (u.a. Untersuchung der Hirnstammreflexe). Im Rahmen eines Vorversuchs wurde eine Status quo-Erhebung von Stichblutmenge- und anstieg durchgeführt und die ersten fünf Sekunden nach dem Entblutestich als geeigneter Messzeitraum festgelegt. Es konnte gezeigt werden, dass der Anstieg der Entblutekurve in diesem Zeitraum annähernd linear verläuft, unabhängig von Lebendgewicht und Geschlecht der Tiere ist, und zudem eine gewisse Voraussage über den weiteren Verlauf der Entblutung bzw. die am Ende der Entblutung absolut entzogene Blutmenge zulässt. In der Hauptuntersuchung waren bei keinem Tier deutliche Anzeichen für Empfindungs- und Wahrnehmungsvermögen (gerichtete Augenbewegungen, Vokalisation) vorhanden. 3,6 Prozent (Prototyp-Untersuchung) bzw. 3,7 Prozent (integriertes IR-Sensor-Messsystem) der Tiere zeigten jedoch bei der Verifizierung des Todeseintritts noch bzw. wieder Reaktionen, die zumindest auf eine gewisse (Rest-)Hirnfunktion hindeuteten. Ein signifikanter Zusammenhang zwischen Steigung der Entblutekurve und nachfolgendem Todeseintritt der Tiere konnte weder in der Untersuchung mit dem Prototyp, noch in der Untersuchung mit dem integrierten IR-Sensor-Messsystem dargestellt werden. Die Ursache dafür wird in einer Beeinflussung der Ergebnisse durch tierindividuell unterschiedliche Betäubungstiefen vermutet (irreversibel betäubte Tiere, deren Entblutekurven eine geringe Steigung aufwiesen, die aber trotzdem keine Reaktionen auf der Nachentblutestrecke zeigten). Im Rahmen der vorliegenden Arbeit wurde ein vollständig automatisiertes, mit herkömmlichen Stechkarussellanlagen kompatibles, Entblutekontrollsystem auf Grundlage der Infrarotsensor-Technik entwickelt. Durch die Fokussierung auf die ersten fünf Sekunden nach Setzen des Entblutestichs, ist das Ergebnis bereits verfügbar, wenn sich die Tiere noch in der Reichweite des Stechpersonals befinden, wodurch eine sofortige Nachbearbeitung betroffener Schweine, ohne zusätzlichen Personaleinsatz, ermöglicht wird. Weiterhin erlaubt das berührungslos arbeitende System eine Einzeltierkontrolle, inklusive automatischer Dokumentation der Entblutedaten, bei der sowohl unzureichend als auch versehentlich überhaupt nicht entblutete Schweine erkannt werden. Die Entwicklung des automatisierten Entblutekontrollsystems trägt dazu bei, den Tierschutz bei der Schweineschlachtung zu verbessern und gesetzliche Vorgaben sowie Verbrauchererwartungen im Hinblick auf tierschutzgerechte Fleischgewinnung als Teil der Lebensmittelqualität zu erfüllen.

Methods for collecting behavioral audiograms are often time consuming and require trained, captive subjects. It is more practical to measure hearing sensitivity using electrophysiological methods, such as auditory evoked potential (AEP) testing, in which electrodes measure action potentials in response to acoustic stimuli. These data can be collected in a matter of hours. However, results should be verified through behavioral testing. Current knowledge of marine turtle auditory abilities is based on a few electrophysiological tests. The purpose of this study was to collect and compare behavioral and auditory evoked potential audiograms in a captive adult loggerhead turtle (Caretta caretta). The behavioral audiogram was collected using a go/no-go modified staircase method utilizing 2-second pure-tone stimuli. AEP thresholds were measured underwater using subdermal electrodes placed beneath the frontoparietal scale, dorsal to the midbrain. Action potentials were measured in response to 50 ms tonal stimuli and averaged over a maximum of 1,000 responses. Evoked potential testing yielded thresholds from 100 - 1131 Hz with peak sensitivity at 200 and 400 Hz (110 dB re 1 µPa). Behavioral testing yielded thresholds from 50 - 800 Hz with peak sensitivity at 100 Hz (98 dB re 1 µPa). Behavioral thresholds averaged 8 dB lower than AEP thresholds from 100 to 400 Hz and 5 dB higher at 800 Hz. Results indicate that behavioral and evoked potential techniques are suitable for determining marine turtle hearing sensitivity. AEP testing is a good alternative when dealing with wild or untrained animals and when time is a critical factor.

No description available.

No description available.

Les mécanismes neuronaux contrôlant la respiration sont présentement explorés à l’aide de plusieurs modèles animaux incluant le rat et la grenouille. Nous avons utilisé la lamproie comme modèle animal nous permettant de caractériser les réseaux de neurones du tronc cérébral qui génèrent et modulent le rythme respiratoire. Nous avons d’abord caractérisé une nouvelle population de neurones, dans le groupe respiratoire paratrigéminal (pTRG), une région du tronc cérébral essentielle à la genèse du rythme respiratoire chez la lamproie. Les neurones de cette région sont actifs en phase avec le rythme respiratoire. Nous avons montré que ces neurones possèdent une arborisation axonale complexe, incluant des projections bilatérales vers les groupes de motoneurones du tronc cérébral qui activent les branchies ainsi que des connexions reliant les pTRG de chaque côté du tronc cérébral. Ces résultats montrent que le pTRG contient un groupe de cellules qui active les motoneurones respiratoires des deux côtés et qui pourrait être impliqué dans la synchronisation bilatérale du rythme respiratoire. Nous avons ensuite étudié les mécanismes neuronaux par lesquels le rythme respiratoire est augmenté en lien avec l’effort physique. Nous avons montré que la région locomotrice du mésencéphale (MLR), en plus de son rôle dans la locomotion, active les centres respiratoires pendant la nage, et même en anticipation. Les neurones de la MLR projetant vers les centres locomoteurs et respiratoires sont ségrégés anatomiquement, les neurones localisés plus dorsalement étant ceux qui possèdent des projections vers les centres respiratoires. Nous avons aboli la contribution de la partie dorsale de la MLR aux changements respiratoires en injectant des bloqueurs des récepteurs glutamatergiques localement, sur des préparations semi-intactes. Nous avons montré que lors d’épisodes de nage, une majeure partie de l’effet respiratoire est abolie par ces injections, suggérant un rôle prépondérant des neurones de cette région dans l’augmentation respiratoire pendant la locomotion. Nos résultats confirment que le rythme respiratoire est généré par une région rostrolatérale du pons de la lamproie et montrent que des connexions des centres locomoteurs arrivent directement à cette région et pourraient être impliquées dans l’augmentation respiratoire reliée à l’effort physique. / The neural control of breathing is currently investigated on multiple animal models such as frogs and rats. We have used the lamprey as an experimental model to characterize the brainstem neural networks involved in the genesis and modulation of the respiratory rhythm. We have first characterized a new population of respiratory neurons in the paratrigeminal respiratory group (pTRG). The pTRG is a region that was shown to be essential to respiratory rhythmogenesis in lampreys. We have shown that the pTRG contains a group of neurons with complex axonal arborisations, including bilateral projections to the motoneuron pools of the brainstem that activate gills, as well as bilateral projections connecting the pTRGs on the two sides of the brainstem. These results suggest that pTRG neurons could participate in the descending control of respiratory motoneurons as well as the bilateral synchrony of the respiratory rhythm. We have then studied the neural mechanisms by which respiration is increased during locomotion. We have shown that the mesencephalic locomotor region (MLR), in addition to its role in controlling locomotion, also increases breathing during locomotion. Neurons in the MLR are anatomically segregated, those projecting to the respiratory centers being located more dorsally. We have abolished the contribution of the dorsal part of the MLR to respiratory changes by injecting glutamate receptor blockers locally in semi-intact preparations. We have shown that during swimming episodes, a major part of the respiratory effect is dependent on the dorsal part of the MLR. Our results confirm that the respiratory rhythm is generated by a rostrolateral region in the pons of lampreys and show that connections from locomotor centers can directly activate this region. These connections could be implicated in the increase of breathing activity related to locomotion.