Local Drug Delivery to the Entire Cochlea without Breaching Its Boundaries.

The mammalian cochlea is one of the least accessible organs for drug delivery. Systemic administration of many drugs is severely limited by the blood-labyrinth barrier. Local intratympanic administration into the middle ear would be a preferable option in this case, and the only option for many newly emerging classes of drugs, but it leads to the formation of drug concentration gradients along the extensive, narrow cochlea. The gradients are orders of magnitude and well outside the therapeutic windows. Here we present an efficient, quick, and simple method of cochlear pumping, through large-amplitude, low-frequency reciprocal oscillations of the stapes and round window, which can consistently and uniformly deliver drugs along the entire length of the intact cochlea within minutes without disrupting the cochlear boundaries. The method should facilitate novel ways of approaching the treatment of inner ear disorders because it overcomes the challenge of delivering therapeutics along the entire cochlear length.

The effectiveness of acupuncture compared to loratadine in patients allergic to house dust mites.

Background. The aim of this work was to evaluate the clinical effectiveness of acupuncture and its impact on the immune system in comparison to loratadine in the treatment of persistent allergic rhinitis caused by house dust mites. Methods. In this study, 24 patients suffering from persistent allergic rhinitis induced by house dust mites were treated either with acupuncture (n = 15) or with loratadine (n = 9). The evaluation of the data was based on the subjective and the objective rhinoconjunctivitis symptom scores, specific and total IgE, and interleukins (IL-4, IL-10, and IFN- γ ) as markers for the activity of Th1 or Th2 cells. Results. The treatments with acupuncture as well as with loratadine were considered effective in the patients' subjective assessment, whereby the effect of the acupuncture tended to be assessed as more persistent after the end of treatment. A change in the specific or the total IgE was not detectable in either group. The interleukin profile showed the tendency of an increasing IL-10 value in the acupuncture group. The results of the study show that the effectiveness of acupuncture is comparable to that of loratadine. Conclusion. Acupuncture is a clinically effective form of therapy in the treatment of patients suffering from persistent allergic rhinitis. The results indicate the probability of an immunomodulatory effect.

A novel mechanism of cochlear excitation during simultaneous stimulation and pressure relief through the round window.

The round window (RW) membrane provides pressure relief when the cochlea is excited by sound. Here, we report measurements of cochlear function from guinea pigs when the cochlea was stimulated at acoustic frequencies by movements of a miniature magnet which partially occluded the RW. Maximum cochlear sensitivity, corresponding to subnanometre magnet displacements at neural thresholds, was observed for frequencies around 20 kHz, which is similar to that for acoustic stimulation. Neural response latencies to acoustic and RW stimulation were similar and taken to indicate that both means of stimulation resulted in the generation of conventional travelling waves along the cochlear partition. It was concluded that the relatively high impedance of the ossicles, as seen from the cochlea, enabled the region of the RW not occluded by the magnet, to act as a pressure shunt during RW stimulation. We propose that travelling waves, similar to those owing to acoustic far-field pressure changes, are driven by a jet-like, near-field component of a complex pressure field, which is generated by the magnetically vibrated RW. Outcomes of research described here are theoretical and practical design principles for the development of new types of hearing aids, which use near-field, RW excitation of the cochlea.

Tonotopic morphometry of the lamina reticularis of the guinea pig cochlea with associated microstructures and related mechanical implications.

Morphometry of the lamina reticularis of the guinea pig cochlea was performed using scanning electron microscopy. Seventy-four geometrical parameters of the lamina reticularis, the bundles of stereocilia, and individual stereocilia, in all rows of hair cells and within the individual hair cells, were measured at ten equally spaced locations along the longitudinal direction of the cochlea. Variations of the parameters versus the longitudinal coordinate were statistically analyzed and fitted with polynomials (constant, linear, or quadratic). Our data show that a unique set of geometrical parameters of inner and outer hair cells is typical for every frequency-dependent position at the lamina reticularis. Morphology of the outer hair cell structures varies more than respective parameters of the inner hair cells. Mechanical modeling using the obtained geometrical parameters provides a novel glance at the mechanical characteristics with respect to the cochlear tonotopy.

Acupuncture in allergic rhinitis: A Mini-Review.

Acupuncture is a therapy method known for millennia with apparently polygenetic roots. It is traditionally practiced in East Asian countries. During the recent fifty years, it has found wide applications in Europe as well. Today acupuncture is one of the most important parts of modern complementary medicine. Questions concerning the mechanism of action and efficacy of acupuncture, among others in the treatment of allergic rhinitis, still lead to many scientific discussions. This review summarizes the modern understanding of possible mechanisms of acupuncture as well as it presents the current state of clinical studies relating to the efficacy of acupuncture in the treatment of allergic rhinitis. Further investigations are necessary to confirm acupuncture as an effective therapy of allergic rhinitis.

A segmentation method to obtain a complete geometry model of the hearing organ.

We present a method for obtaining a complete geometry model of the fluid chambers of cochlea (scalae) from tomography images. An accurate segmentation of cochlea is problematic due to the low contrast of the inner membranes of scalae. Our method of 3D segmentation is based on dynamic resampling of an original image stack to achieve a perpendicular cross-section of the scalae on all sections. Subsequently, perpendicular cross-section is being segmented using 2D active contours. The center of mass of the contour is extracted and used to predict further course of scalae centerline by Kalman filter. Cross-section contours are subsequently assembled to the total geometry model. This method has been applied to CT images, but we expect that it could be used for segmentation of strongly curved low-contrast tubular objects recorded with other tomography techniques.

Tuning of synapse number, structure and function in the cochlea.

Cochlear inner hair cells (IHCs) transmit acoustic information to spiral ganglion neurons through ribbon synapses. Here we have used morphological and physiological techniques to ask whether synaptic mechanisms differ along the tonotopic axis and within IHCs in the mouse cochlea. We show that the number of ribbon synapses per IHC peaks where the cochlea is most sensitive to sound. Exocytosis, measured as membrane capacitance changes, scaled with synapse number when comparing apical and midcochlear IHCs. Synapses were distributed in the subnuclear portion of IHCs. High-resolution imaging of IHC synapses provided insights into presynaptic Ca(2+) channel clusters and Ca(2+) signals, synaptic ribbons and postsynaptic glutamate receptor clusters and revealed subtle differences in their average properties along the tonotopic axis. However, we observed substantial variability for presynaptic Ca(2+) signals, even within individual IHCs, providing a candidate presynaptic mechanism for the divergent dynamics of spiral ganglion neuron spiking.

The creation of geometric three-dimensional models of the inner ear based on micro computer tomography data.

The modeling of the mechanical process of hearing requires an accurate geometrical model of the inner ear (cochlea). The purpose of this study was the creation of a 3-D model of the fluid chambers of Guinea pig cochlea, which could serve as a basis for further mechanical modeling. Micro computer tomography used in this study is a noninvasive method to visualize bony structures. The visualization of the membranous labyrinth was achieved by additional staining of the specimen with OsO(4). The resulting stack of images has been transformed into a cylindrical coordinate system. To suppress noise on tomography images, a nonlinear smoothing method, anisotropic diffusion, were applied. A new approach has been proposed to estimate algorithm parameters automatically. Then, a segmentation using active contours (snakes) was performed. In this study, a new energy linking the contours on adjacent slices has been added to the standard approach. This compensates the inconsistencies between adjacent contours. The images segmented in this way were used as a basis for a 3-D reconstruction of the hearing organ.

Argon protects hypoxia-, cisplatin- and gentamycin-exposed hair cells in the newborn rat's organ of Corti.

During the last few years, an important protective effect of the noble gas xenon against neuronal hypoxic damage was observed. However, argon (Ar), a gas from the same chemical group, but less expensive and without anesthetic effect at normobaric pressure, has not been studied in terms of possible biological effects on cell protection. Ar was tested for its ability to protect organotypic cultures of the organ of Corti from 3-5 day old rats against hypoxia, cisplatin, and gentamycin toxicity. Cultures were exposed to nitrogen hypoxia (5% CO2, 95% N2), Ar hypoxia (5% CO2, 95% Ar) or normoxia for 30 h. Ar protected the hair cells from hypoxia-induced damage by about 25%. Ar-oxygen (O2) mixtures (21% O2, 5% CO2, 74% Ar) had no effect on the hair cell survival. Cisplatin (7.5-25 microM) and gentamycin (5-40 microM) exposed in medium under air damaged the hair cells in a dose-dependent manner. The exposure of cisplatin- and gentamycin-treated cultures to the Ar-O2 atmosphere significantly reduced the hair cell damage by up to 25%. This protective effect of Ar might provide a new protective approach against ototoxic processes.