Calpains, a family of calcium activated proteases, promote the breakdown of cellular proteins, kinases, phosphatases and transcription factors. Calpain inhibitors attenuate some neurodegenerative processes in certain cell types. Here we show that leupeptin, a potent calpain inhibitor, protects the sensory hair cells in the inner ear from acoustic overstimulation (48 h, 100 or 105 dB SPL, octave band noise at 4 kHz). Acoustic overstimulation caused a significant increase in calpain immunolabeling in the sensory epithelium suggesting a possible role in noise-induced cochlear degeneration. Infusion of leupeptin into the inner ear significantly reduced the amount of sensory cell loss from acoustic overstimulation. However, leupeptin did not protect against hair cell loss from the ototoxic drug, carboplatin.

A randomized controlled study using benzodiazepines to treat patients with chronic subjective tinnitus was performed to determine if these drugs could suppress intractable tinnitus. Trials with the antihistames meclizine, chlorpheniramine, and dexchlorpheniramine were used as the controls in the evaluation of diazepam, flurazepam, carbamazepine, oxazepam, and clonazepam. Of all the benzodiazepines studied, only oxazepam and clonazepam were significantly more effective than antihistamines in suppressing chronic tinnitus, but these two drugs alleviated the symptom in 52 per cent and 69 per cent of the individuals treated respectively. Oxazepam 30 milligrams daily or clonazepam 0.5 milligrams three times daily provides substantial control of chronic tinnitus.

Central tinnitus is defined as an abnormal sensation of sound which is perceived by the patient and established by neurotologic diagnosis to be retrocochlear and/or within the central nervous system in location. A method of diagnosis and evaluation using evoked response audiometry (ABR) is reported. A clinical test, Simultaneous Binaural Auditory Brain responses with monaural stimulation (ABR) for central location of tinnitus is presented. The use of a diagnostic approach to the selection of a tinnitus masker will be presented. Electrophysiologic indices for central tinnitus have been observed based on short latency ABR recordings. A classification has been presented. The use of lidocaine I.V. therapy with ABR recordings is presented. The concept, diagnosis, and techniques at this time, relating to central tinnitus, are presented as clinical observations. These observations are a beginning for the establishment of an electrophysiologic series of indices which can be interpreted as an electrophysiologic correlate of tinnitus to be supported by basic clinical research.

A new method of electrical tinnitus control employs sine-wave frequencies, slowly varying between 0.2 and 20 kHz and modulating a 60 kHz carrier. The latter literally carries the audio-frequencies "under the skin" via external electrodes placed on both mastoids. Patients undergo exposure at home. The dosis increases from 1 h/day to maximally 5 h/day. Suppression is achieved in about 60% of selected patients. Once tinnitus is under control, usually after 3-5 sessions, exposure may be reduced.

No abstract

No abstract

Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) are neurodegenerative disorders of the aging population characterized by the accumulation of α-synuclein (α-syn). The mechanisms triggering α-syn toxicity are not completely understood, however, c-terminus truncation of α-syn by proteases such as calpain may have a role. Therefore, inhibition of calpain may be of value. The main objective of this study was to evaluate the effects of systemically administered novel low molecular weight calpain inhibitors on α-syn pathology in a transgenic mouse model. For this purpose, non-tg and α-syn tg mice received the calpain inhibitors - Gabadur, Neurodur or a vehicle, twice a day for 30 days. Immunocytochemical analysis showed a 60% reduction in α-syn deposition using Gabadur and a 40% reduction using Neurodur with a concomitant reduction in c-terminus α-syn and improvements in neurodegeneration. Western blot analysis showed a 77% decrease in α-spectrin breakdown products (SBDPs) SBDPs with Gabadur and 63% reduction using Neurodur. There was a 65% reduction in the active calpain form with Gabadur and a 45% reduction with Neurodur. Moreover, treatment with calpain inhibitors improved activity performance of the α-syn tg mice. Taken together, this study suggests that calpain inhibition might be considered in the treatment of synucleinopathies.

No abstract