Gap junction channels which are responsible for direct intercellular communication are composed of connexin proteins. Different connexins are distributed in a tissue-specific manner. Up to now only connexin26 has been identified to be widely expressed in the inner ear. In order to investigate the role of additional gap junction proteins, the expression of connexin30 and 43 was investigated in the rat cochlea. Connexin26 and connexin30 were both expressed in the spiral limbus, the spiral ligament, the stria vascularis and between supporting cells of the organ of Corti. Double-labeling experiments suggest that both connexins are partly colocalized between cells. Weak staining of connexin43 could only be detected in the stria vascularis, the spiral ligament and between organ of Corti supporting cells. The corresponding transcripts for connexin26, 30 and 43 could be detected by Northern blot analysis. The expression of different gap junction channels in the cochlea suggests functional diversity. Gap junctions in the inner ear may control ion concentrations of cochlear fluids or act as conduits through which glucose and other metabolites diffuse.

The gap junction protein connexin30 (Cx30) is expressed in a variety of tissues that include epithelial and mesenchymal structures of the inner ear. We generated Cx30 (Gjb6) deficient mice by deletion of the Cx30 coding region. Homozygous mutants (Cx30((-/-))) were born at the expected Mendelian frequency, developed normally and were fertile. However, they exhibit a severe constitutive hearing impairment. From the age of hearing onset, these mice lack the electrical potential difference between the endolymphatic and perilymphatic compartments of the cochlea, i.e. the endocochlear potential, which plays a key role in the high sensitivity of the mammalian auditory organ. In addition, after postnatal day 18, the cochlear sensory epithelium starts to degenerate by cell apoptosis. This degeneration process is likely to account for the concomitant decrease of the endolymphatic potassium concentration and the aggravation of the hearing loss in adult Cx30((-/-)) mice. The Cx30 ((-/-)) phenotype thus reveals the critical role of Cx30 both in generating the endocochlear potential and for survival of the auditory hair cells after the onset of hearing. The Cx30 deficient mice may represent a valuable model to study the mechanism of the hearing loss in human patients carrying a homozygous deletion of the CX30 gene (del Castillo et al., 2002, New Engl. J. Med., 346, 243-249).

C-HART (70.6 Gy) is superior to dose-escalated HART (77.6 Gy) with comparable or less acute reactions and equivalent late reactions, indicating an improvement of the therapeutic ratio.

There is a controversy about the biocompatibility of silicon nitride ceramics contained in the literature, which appears to be related to a factor of the individual chemical composition of different qualities of silicon nitride ceramics and of the different surface properties. This study attempts to investigate the cytotoxicity of different qualities of industrial silicon nitride ceramics applying an L929-cell culture model in a direct contact assay combined with a cell viability assessment. Five different qualities of industrial standard silicon nitride ceramics were chosen for in vitro testing. The chemical composition was determined by EDS analysis. Different biomedically approved aluminium oxide qualities, a titanium alloy, glass and polyvinylchloride (PVC) served as control materials. L929 mice fibroblasts were incubated directly on the materials for 24 h, stained with bisbenzimide and propidium iodine for double fluorochromasia viability testing, and evaluated by inversion-fluorescence microscopy to control cell morphology, viability and cell counts compared to empty well values. Scanning electron microscopy was applied to additionally investigate cell morphology. There was no observation of cytotoxic effects on the silicon nitride ceramic samples; moreover cell morphology remained the same as on aluminium oxide and titanium. Viability testing revealed the presence of avital cells exclusively on PVC, which served as a negative control. Cell counts on all polished surfaces showed significantly higher numbers, whereas some rough surface samples showed significantly lower numbers. We conclude that silicon nitride ceramics show no cytotoxic effects and should be considered for biomedical application owing to its favourable physiochemical properties, especially its superior resistance to mechanical stress, which would be useful for compression loaded conditions. Polished surfaces would appear to promote advanced biocompatibility.

Congenital sensorineural hearing loss affects approximately 1/1,000 live births. Mutations in the gene encoding connexin26 (GJB2) have been described as a major cause of genetic nonsyndromic hearing impairment. Additionally, another gap junction gene, connexin30 (GJB6), was found to be responsible for hereditary hearing loss. We have studied 134 patients with severe to profound hearing loss or deafness and 13 patients with mild to moderate nonsyndromic sensorineural hearing loss in order to evaluate the prevalence of connexin26 and connexin30 mutations in Germany. Mutations in the connexin26 gene were found in 30 patients (22%) with profound to severe hearing impairment whereas only one novel single nucleotide polymorphism (396G-->A) in the connexin30 gene was detected. Among the 13 patients with mild to moderate hearing loss neither mutations in the connexin26 nor in the connexin30 gene could be detected. These results demonstrate that mutations in the connexin26 gene are also a frequent cause of hereditary non-syndromic hearing loss in Germany. Therefore a screening of mutations in the connexin26 gene should be performed in every case of non-syndromic hearing loss of unknown origin.