A model portraying experimental loss of hair cell: the use of distortion product otoacoustic emission in the assessment of rat's ear.

The use of rats in research academies to study deafness is widespread, meanwhile medicinal methods to eliminate hair cells is also increasing. Thus, aminoglycosides and loop diuretics have grasped more attention. This study aimed at establishing an animal model in which a rapid distortion of the hair cell of cochlea administering amikacin and furosemide and using distortion product otoacoustic emission (DPOAE) the functioning of rat's ear would be assessed. Forty-eight male Sprague-Dawley rats (mean weight 200-250g) were randomly divided into six equal groups. Except the control group the rest received 0.5mg/g, 0.75mg/g, 1mg/g, 1.25mg/g, and 1.5mg/g, of subcutaneous amikacin respectively. 30 minutes later every rat received 0.1mg/g of furosemide intrapritoneally. DPOAE of rats was measured before these injections and 72 hours later. Then tissue sections of the rat's cochlea were prepared. All the cases had a significant decrease in their DPOAE with the frequencies 2KHz-8KHz (p<0.05). The most change in DPOAE was in rats which had received 1mg/g - 1.5mg/g amikacin. Histological studies approved distortion of hair cell even the apical turn. To establish a deafness model due losing hair cells, it is possible to use a combination of 1mg/g amikacin and 0.1mg/g furosemide. Besides, to approve deafness DPOAE resulted can be used.

Tobramycin for nebulisation: new formulation. A high price for a small improvement in formulation.

(1) In patients with cystic fibrosis, chronic bronchial infection with Pseudomonas aeruginosa is a major factor in the development of chronic respiratory failure and premature death. (2) Over the last two decades, such patients have commonly received long-term treatment with antibiotic aerosols (mainly tobramycin or colistin, in off-licence uses). (3) Tobramycin solution for nebulisation is the first antibiotic preparation to be licensed in the EU for this indication. (4) Comparative evaluation of antibiotic aerosol therapy for chronic bronchial infections due to P. aeruginosa includes two large trials of nebulised tobramycin. (5) A combined analysis of these two placebo-controlled trials, both lasting 20 weeks, showed that tobramycin aerosol delayed the deterioration of respiratory function and reduced the number of hospitalisations. However, an increase in P. aeruginosa resistance to tobramycin was reported. (6) The file on tobramycin includes no precise criteria for stopping treatment, and no data on the long-term impact of the observed increase in bacterial resistance. (7) The main adverse effects of tobramycin aerosol are tinnitus and voice changes. Deafness has also been reported. (8) The available assessment file does not show whether the risk-benefit ratio of tobramycin aerosol differs from that of other nebulised antibiotics used (off-licence) in this setting. However, tobramycin is the best-assessed nebulised antibiotic for this indication. (9) In practice, tobramycin solution for nebulisation may be considered the reference long-term treatment for chronic pulmonary infections due to P. aeruginosa in patients with cystic fibrosis. Assessment should continue, however, especially regarding the possible impact on mortality and the selection of resistant strains.

In vitro and in vivo assessment of the ability of adeno-associated virus-brain-derived neurotrophic factor to enhance spiral ganglion cell survival following ototoxic insult.

OBJECTIVES/HYPOTHESIS: Auditory dysfunction following ototoxic insult results from loss of cochlear hair cells. Secondary degeneration of auditory neurons ensues from withdrawal of neurotrophic support from hair cells and can be prevented with administration of neurotrophins. Administration of adeno-associated virus containing the gene for brain-derived neurotrophic factor will promote spiral ganglion neuron survival after the destruction of hair cells. METHODS: Prevention of aminoglycoside-induced spiral ganglion neuron loss through the expression of brain-derived neurotrophic factor mediated by means of the adeno-associated virus was tested in vitro in cochlear explants and in vivo in mammalian cochlea. RESULTS: Neuronal survival was significantly enhanced in adeno-associated virus-brain-derived neurotrophic factor transfected rat cochlear explants compared with control samples (30% vs. 19%, P <.05) following exposure to aminoglycoside. Following deafening with aminoglycoside and loop diuretic and introduction of adeno-associated virus-brain-derived neurotrophic factor through osmotic minipump, the experimental group of animals infused with adeno-associated virus-brain-derived neurotrophic factor displayed enhanced spiral ganglion neuron survival in the basal turn of the cochlea when compared with the control group infused with adeno-associated virus containing green fluorescent protein reporter gene. CONCLUSIONS: Administration of adeno-associated virus-brain-derived neurotrophic factor enhances spiral ganglion neuron survival following ototoxic exposure in vitro and in vivo. These studies lay the groundwork for further exploration of its application as an adjunct therapy for patients undergoing cochlear implantation because the success of implantation depends directly on the population of neurons available for electrical stimulation.

Aminoglycoside antibiotics in clinical use.

Aminoglycosides are among the most used antibiotics despite competitive pressure from newer beta-lactam agents. The activity profile, pharmacology, toxicity potential, and methods of toxicity prevention of aminoglycosides are well appreciated after three decades. Nephrotoxicity, ototoxicity, and the added costs of drug level monitoring limit wider usage, but great activity against highly antibiotic resistant gram negative bacteria often outweigh these disadvantages and will likely keep aminoglycosides available for the foreseeable future.