[The influence of different alpha-sympathomimetic drugs and benzalkoniumchlorid on the ciliary beat frequency of in vitro cultured human nasal mucosa cells]. / Der Einfluss verschiedener alpha-Sympathomimetika und Benzalkoniumchlorid auf die Zilienschlagfrequenz humaner Flimmerzellen in vitro.

BACKGROUND: An appropriate in-vitro model of the human nasal mucosa was developed, which allowed to measure the influence of different pharmaceutical substances on the ciliary beat frequency (CBF) under standardized conditions. METHOD: The present study describes the effect of the alpha-sympathomimetic drugs naphazolin, xylometazolin and oxymetazolin as pure substances and the preservative Benzalkonium chloride in rising concentrations on the CBF. For these investigations human cells of the human nasal mucosa were cultured, which exhibited a high constancy during the equilibration measurements over at least 200 minutes. RESULTS: The alpha-sympathomimetic drugs oxymetazoline in the concentration of 0.01% and 0.001% as well as naphazoline within all three concentrations did not show any change of the CBF. Whereas xylometazoline in the concentration of 0.1% caused a high-significant decrease of the CBF. This decrease of the CBF was however partially reversible after rinsing out. Oxymetazolin showed likewise a significant decrease of the CBF in the concentration of 0.1%. This effect however was not reversible after rinsing out with substrate-free medium, but on the contrary showed up a further decrease of CBF. The preservative benzalkonium chloride effected an irreversible ciliostatic activity already in the concentration of 0.005%. CONCLUSIONS: From the three investigated alpha-sympathomimetic drugs only naphazoline in all measured concentrations did not show any toxic effect. With regard to its therapeutic application this drug in the concentrations 0.001%-0.1% should be preferred to all other alpha-sympathomimetic drugs. Oxymetazoline in the concentration of 0.01% and 0.001% had no toxic effect as well. It however caused an irreversible damage to the cilia in the concentration of 0.1%. This should be considered for the application of rhinological drugs especially in children. The same attention is demanded for xylometazoline, causing a high significant release of CBF in the concentration of 0.1%, which is only partially reversible. Due to the results of this study it has strongly to be advised against the use of all rhinological drugs containing the preservative benzalkonium chloride.

A new approach to pharmacological effects on ciliary beat frequency in cell cultures--exemplary measurements under Pelargonium sidoides extract (EPs 7630).

The ciliary beat frequency (CBF) is an important parameter of the defence mechanism of the mucociliary system. We present a new method to determine pharmacological effects on CBF in vitro. Ciliated cell cultures of human nasal epithelium were obtained from partial resection of hyperplastic inferior turbinates in rhinosurgery. An adherent monolayer culture of ciliated cells was present after 10 days in vitro. This study exemplary examines, if a special extract from the roots of Pelargonium sidoides (EPs 7630) has an effect on the CBF in vitro. The influence of three concentrations of the extract (1, 30, 100 microg/ml) was tested. EPs 7630 significantly and concentration-dependently increased CBF to 123% at 30 microg/ml and to 133% at 100 microg/ml compared to the equilibration phase (100%). After rinsing with extract-free medium the CBF of cultured cells returned to nearly the normal range. In future, drug manipulation of the CBF by local application of rhinologics could be a new therapeutical concept in the treatment of upper airway diseases.

[Standardized measurement of sound transmission of different middle ear prostheses]. / Standardisierte Messungen der Schallübertragung verschiedener Mittelohrprothesen.

The sound transmission properties of three different commercially available middle ear implants and the prototype of a complete middle ear prosthesis (CoMEP) were evaluated with a special measurement system that permits standardized conditions. This system uses a mechanical middle ear model (MMM) which approximates the impedances of the tympanic membrane and inner ear. The implants were fitted under defined conditions into the MMM. Displacement of the artificial stapes footplate of the MMM was measured with an optical probe. The measurements of different middle ear prostheses showed that the mass of the implant was the most important factor for optimum high frequency transmission. The lightest implant (4 mg, titanium) showed the best results. The CoMEP revealed the highest sensitivity because of a slight enlargement of the diameter of the artificial tympanic membrane. These findings show that the CoMEP is able to restore sound transmission to a normal range. In a second experiment one of the implants was fitted into the MMM with different forces. The increase of stiffness produced a slightly better high frequency transmission at the expense of low frequency sensitivity. Hence, the fitting of the implant may not be too stiff because of its loss of mobility within a significant frequency range.

[Using the Mongolian gerbil (Meriones unguiculatus) as an animal model in ontogenetic cochlear implant research]. / Einsatz der mongolischen Wüstenrennmaus (Meriones unguiculatus) als Tiermodell in der ontogenetischen Kochleaimplantatforschung.

One of the problems when providing prelingually deafened children with a cochlear implant is to find the optimal moment for the implantation in order to make optimal use of the sensitive phase in the maturation of the auditory system and to achieve the maximum improvement of hearing. Ontogenetic questions can be investigated in animal experiments under controlled conditions. In the present study an animal model (gerbil, Meriones unguiculatus) was established to simulate the situation of prelingually deafened children and to examine the influence of chronic electrostimulation on the development of the auditory pathway. We used species specific sounds for chronic stimulation to simulate significance of human language in our animal modell. A daily two-hour electrostimulation during the ontogenesis of early deafened animals lead to a partial compensation of the functional degeneration of the auditory pathway, which can be observed in totally deafened animals. This animal model provides an elaborate test design which can be used in CI research for the investigation of numerous problems.

Standardized measurements of the sound transmission of middle ear implants using a mechanical middle ear model.

Several ways to evaluate the sound transmission properties of middle ear implants are now established. Besides computer-based simulations using acoustic and electrical analog circuits or finite element analysis, measurements can be performed with temporal bone preparations. Experiments with these preparations consider various anatomical properties, but a large number of parameters influence the outcome of measurements. To facilitate standardized measurements, a mechanical middle ear model was developed that allows comparison of the transfer function of middle ear implants on defined conditions. The model approximates the impedances of the tympanic membrane and inner ear with the aid of thin, flexible membranes. The implants are fit between the membranes, and displacement at an artificial stapes foot-plate is measured with an optical probe. Fundamental influences on the sound transmission properties of nine different middle ear implants (total ossicular replacement prostheses) were examined. Although the material and shape were different, some of the prostheses revealed very similar transfer functions. The mass of the implant showed the largest influence on sound conduction. With a higher mass, the frequency area above approximately 1 kHz was found to be significantly deteriorated. The lightest implant used was 4 mg and showed the best overall results. These findings show that middle ear prostheses should be as light as possible for optimum high-frequency transmission.

[Measuring vibration properties of middle ear implants with the mechanical middle ear model. Initial results]. / Messung der Schwingungseigenschaften von Mittelohrimplantaten mit einem mechanischen Mittelohrmodell. Erste Ergebnisse.

With the aid of a mechanical middle ear model (MMM) the sound transmission properties of different middle ear implants were investigated. Input of the MMM involved a broad-band signal from 100 to 5000 Hz that was supplied by a miniaturized loudspeaker. Displacement of an artificial stapes footplate was measured by a fiberoptic probe. The transfer functions of four different total ossicular replacement prostheses (TORPs) of different materials and shapes were compared. Three of the devices revealed similar transfer functions which corresponded to the typical curve of the normal middle ear. One of the prostheses demonstrated a high-frequency deterioration of approximately 5 dB. This effect was explained by a 3- to 6-times higher mass of the implant when compared to the others. Altogether, the weight of the prosthesis seems to have the most marked impact on sound transmission to the inner ear, whereas stiffness of the implant itself is less crucial as long as it can be regarded as a rigid body.

[A registration system for evaluating acusto-mechanical transmission of middle ear implants]. / Ein Messsystem zur Uberprüfung des akustomechanischen Ubertragungsverhaltens von Mittelohrimplantaten.

A measurement system was developed that permits objective comparisons of the sound conduction of middle ear implants. The implants are fitted into a mechanical middle ear model which approximates the impedances of the eardrum and the inner ear. A defined signal within the frequency range of 0-5 kHz is provided by a miniaturized loudspeaker at the input to the model and is measured by a probe microphone. Displacement of an artificial stapes footplate at the output of the model is measured by a fiberoptic probe with a sensitivity of 5 nm. The transmission function is calculated as the quotient of the output and the input signal. This system can be used to evaluate the sound-transmitting properties of different middle ear implants excepting other influences, such as surgical techniques. This work details the measurement system and demonstrates basic influences on the sound-transmission of middle ear implants.