Hearing relies on faithful sound coding at hair cell ribbon synapses, which use Ca 2ϩ -triggered glutamate release to signal with submillisecond precision. Here, we investigated stimulus-secretion coupling at mammalian inner hair cell (IHC) synapses to explore the mechanisms underlying this high temporal fidelity.

Cochlear inner hair cells (IHCs) release neurotransmitter onto afferent auditory nerve fibers in response to sound stimulation. During early development, afferent synaptic transmission is triggered by spontaneous Ca2+ spikes of IHCs, which are under efferent cholinergic control. Around the onset of hearing, large-conductance Ca2+-activated K+ channels are acquired, and Ca2+ spikes as well as the cholinergic innervation are lost. Here, we performed patch-clamp measurements in IHCs of mice lacking the CaV1.3 channel (CaV1.3-/-) to investigate the role of this prevailing voltage-gated Ca2+ channel in IHC development and synaptic function. The small Ca2+ current remaining in IHCs from 3-week-old CaV1.3-/- mice was mainly mediated by L-type Ca2+ channels, because it was sensitive to dihydropyridines but resistant to inhibitors of non-L-type Ca2+ channels such as omega-conotoxins GVIA and MVIIC and SNX-482. Depolarization induced only marginal exocytosis in CaV1.3-/- IHC, which was solely mediated by L-type Ca2+ channels, whereas robust exocytic responses were elicited by photolysis of caged Ca2+. Secretion triggered by short depolarizations was reduced proportionally to the Ca2+ current, suggesting that the coupling of the remaining channels to exocytosis was unchanged. CaV1.3-/- IHCs lacked the Ca2+ action potentials and displayed a complex developmental failure. Most strikingly, we observed a continued presence of efferent cholinergic synaptic transmission and a lack of functional large-conductance Ca2+-activated K+ channels up to 4 weeks after birth. We conclude that CaV1.3 channels are essential for normal hair cell development and synaptic transmission.

Hearing and balance rely on the faithful synaptic coding of mechanical input by the auditory and vestibular hair cells of the inner ear. Mechanical deflection of their stereocilia causes the opening of mechanosensitive channels, resulting in hair cell depolarization, which controls the release of glutamate at ribbon-type synapses. Hair cells have a compact shape with strong polarity. Mechanoelectrical transduction and active membrane turnover associated with stereociliar renewal dominate the apical compartment. Transmitter release occurs at several active zones along the basolateral membrane. The astonishing capability of the hair cell ribbon synapse for temporally precise and reliable sensory coding has been the subject of intense investigation over the past few years. This research has been facilitated by the excellent experimental accessibility of the hair cell. For the same reason, the hair cell serves as an important model for studying presynaptic Ca(2+) signaling and stimulus-secretion coupling. In addition to common principles, hair cell synapses differ in their anatomical and functional properties among species, among the auditory and vestibular organs, and among hair cell positions within the organ. Here, we briefly review synaptic morphology and connectivity and then focus on stimulus-secretion coupling at hair cell synapses.

Propofol-MCT/LCT produced significantly less pain on injection when compared to standard propofol in ASA I and II patients undergoing elective surgery. Pain was also significantly less severe, with both effects presumably being due to the lower concentration of free propofol in the MCT/LCT-preparation. With regard to injection pain propofol-MCT/LCT offers significant a advantage over standard propofol.

Hearing impairment is the most common form of human sensory deficit. The most frequent form, sensorineural hearing loss (SNHL), which accounts for approximately 70% of cases, encompasses various pathologies in both the inner ear and the auditory nerve. The individual hearing impairment and its outcome following aiding with hearing devices critically depend on the underlying disorder. Here recent progress in our understanding of the cellular mechanisms of SNHL in genetically engineered mouse models is reviewed. First, insights gained from models for specific defects in cochlear sound amplification and ion homeostasis are discussed followed by a focus on disorders of the inner hair cell synapses (auditory synaptopathy) and the auditory nerve (auditory neuropathy). Both nosological entities have also attracted substantial clinical interest in recent years and share an impaired temporal processing of auditory stimuli. This results in poor speech recognition, often out of proportion to the pure tone threshold. Hearing loss can range from mild variants with exclusive deficits of temporal processing to complete deafness. At least initially, signs of normal outer hair cell function such as evoked otoacoustic emissions can be found. In summary, well-characterized animal models allow us to refine our pathophysiological understanding of SNHL and offer invaluable help in defining toolboxes for investigating the mechanism(s) underlying the SNHL of affected individuals. Together, this will contribute to custom-tailored diagnostics and rehabilitation of SNHL patients.

Within the pharmaceutical industry and in biotechnology there is an increasing need for selective and efficient separation technologies to isolate and purify value-added products. A hybrid process approach combining chromatography and fractional crystallization is studied below. The work presented is concerned with the application and evaluation of this concept in order to isolate a certain pharmaceutical intermediate from a binary mixture. A comparison with performing the same separation exclusively in a single chromatographic process is given also.

The economic value of tiotropium in patients with moderate to severe COPD was analysed in a cost-effectiveness study for the Swiss public health insurance system. The results show a drop in COPD exacerbations in comparison to Ipratropium, Salmeterol and standard care (without use of anticholinergics and beta-adrenergics). The numbers-needed-to-treat of tiotropium in comparison to the other medications in order to avoid severe exacerbations amounted to 8 patients (ipratropium versus tiotropium), 13 patients (standard care versus tiotropium) and 33 patients (salmeterol versus tiotropium) during 12 months. As a result fewer episodes of hospitalisations and shorter hospital stays can be expected. The direct yearly total cost for COPD therapy is CHF 4788 for tiotropium and CHF 5820 for ipratropium. Furthermore, they amount to CHF 4881 and CHF 4920 for salmeterol and standard care. The higher acquisition cost for tiotropium is compensated by fewer exacerbations. No other medication was similarly cost-effective with regard to total cost and number of exacerbations.

Possible complications of parotid gland surgery are numerous, just as the reasons for aneurysms of the superficial temporal artery. The occurrence of such an aneurysm as a consequence of parotidectomy, however, has so far only been published once. Here, we report of an aneurysm of the superficial temporal artery following parotid gland surgery. It presented as a pulsating mass in the preauricular region. Combining clinical examination, duplex ultrasound, and CT scan, the diagnosis was readily established and treated with a circumscribed revision at low risk and without complications.