Various devices have been developed to overcome the widespread phenomenon of different degrees of hearing deficits between mild and profound hearing loss. Basically, we differentiate between acoustic stimulation (hearing aids), restricted to cases with a partially functioning cochlear receptor, and electrical stimulation (cochlear implants), stimulating the auditory nerve directly in cases with profound or total hearing loss. For the first time, animal data have been collected that indicate the possibility of nearly interference-free use of both stimulation types simultaneously. In addition, we have gathered the first clinical patient experience, which confirms the encouraging results. Future implications for patients with severe high-frequency hearing loss are discussed.

Acoustic Stimulation↗

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Plastic changes in the auditory cortex of congenitally deaf cats following cochlear implantation.

Congenitally deaf cats were used as a model for human inborn deafness and auditory deprivation. The deaf cats were supplied with a cochlear implant, chronically exposed to an acoustic environment and conditioned to acoustic stimuli. In case of early implantation the cats learned to make use of the newly gained auditory channel behaviourally. Neurophysiological and fMRI data showed that the central auditory system was recruited, if implantation took place within a sensitive period of <6 months.

Animals↗

PubMedDate not supplied

Delayed maturation and sensitive periods in the auditory cortex.

Behavioral data indicate the existence of sensitive periods in the development of audition and language. Neurophysiological data demonstrate deficits in the cerebral cortex of auditory-deprived animals, mainly in reduced cochleotopy and deficits in corticocortical and corticothalamic loops. In addition to current spread in the cochlea, reduced cochleotopy leads to channel interactions after cochlear implantation. Deficits in corticocortical and corticothalamic loops interfere with normal processing of auditory activity in cortical areas. Thus, the deprived auditory cortex cannot mature normally in congenital deafness. This maturation can be achieved using auditory experience through cochlear implants. However, implantation is necessary within the sensitive period of the auditory system. The functional role of long-term potentiation and long-term depression, inhibition, cholinergic modulation and neurotrophins in auditory development and sensitive periods are discussed.

Age Factors↗

PubMedDate not supplied

Thresholds of intracranially recorded auditory field potentials in the pigeon compared with compound action potential thresholds.

The compound action potential (CAP) thresholds provide a reliable indicator for cochlear functional integrity during experimentation in birds as well as in mammals. However, if experimental manipulations are necessary in the middle ear/inner ear spaces, the round window electrodes are often inconvenient. In search for an alternative for CAP recordings, intracranial recordings of acoustically evoked field potentials from the nucleus angularis/magnocellularis were made in pigeons using stereotactically placed electrodes. The responses were compared with those recorded from intracranial surface electrodes placed on the dura mater and compared with CAP responses recorded from the round window. The field potentials recorded from the nucleus angularis/magnocellularis contain a significant contribution from the auditory nerve, as large in amplitude as the CAP recorded at the round window. The recordings from the intracranial surface electrodes were noisier and the contribution from the auditory nerve was too small to be used as a fast monitor of the condition of the inner ear. Threshold curves as a function of frequency could be determined with an automated method from the nucleus angularis/magnocellularis with the same sensitivity and accuracy as from the round window CAP within a few minutes. These results demonstrate that stereotactic recordings of field potentials from the nucleus magnocellularis/angularis region are a suitable alternative to reliably monitor the condition of the inner ear when round window electrodes cannot be used.

Animals↗

PubMedDate not supplied

Neurotransmitters in the cochlea and the cochlear nucleus.

The inhibitory efferent transmitter in the cochlear is most likely acetylcholine. The afferent transmitter (between hair cells and primary afferent fibres) is not known. There is some evidence for glutamate (or aspartate) but the high concentrations necessary to activate the afferents when these amino-acids are applied intracochlearly may indicate that their effects is unspecific. A number of other transmitter candidates can be safely ruled out at these synapses. In the cochlear nucleus of transmitter between primary afferents and secondary cells is probably glutamate (or aspartate).

Acetylcholine↗

PubMedDate not supplied

Effect of ultraviolet radiation and kinins on oxygen uptake by tissue slices and on basal metabolism in rabbits.

The experiments were carried out on 85 rabbits in 15 groups of 5-8 animals in each. The different groups received: 1) ultraviolet radiation once during 45 minutes or daily during 10 minutes for 6 weeks, 2) bradykinin intravenously 10 microgram/kg, 3) kallikrein 5 B.U./kg intramuscularly during 3 weeks. The levels of kinins and kininogen, and the activity of kallikrein and kininases were determined in the blood several times during 24 hours after radiation exposure, and at intervals of two weeks during long-term exposure to radiation. In the same time periods after exposure the basal metabolism and the uptake of oxygen by slices of the kidneys, liver, heart and skin in vitro were determined. Determinations of aerobic metabolism were carried out also after bradykinin injection and at weekly intervals during kallikrein administration. It was found that: 1) after exposure to ultraviolet radiation there was a high rise in the level of kinins and a fall of kininogen, the activity of kininogenases was raised and that of kininases was decreased, while oxygen uptake was reduced moderately; 2) exogenous bradykinin and endogenous kinins reduced oxygen uptake in vivo and in vitro.

Animals↗

PubMedDate not supplied

Role of quality control in validation of biopharmaceutical processes: case example of clean-in-place (CIP) procedure for a bioreactor.

If ever clear instruction and close teamwork is needed, it is in the validation of manufacturing processes. All members of the Validation Team need to understand how the Quality Control testing fits into the overall validation work plan. This affords the team members the opportunity to understand how data will be used and avoids a situation where the test results either invalidate or inadequately support the validation plan. A case example is presented for an approach used to validate Clean-in-Place (CIP) procedures for 1600 L bioreactors which are operated on a campaign basis for multi-biopharmaceutical synthesis.

Chromatography, High Pressure Liquid↗