Inflammation up-regulates cochlear expression of TRPV1 to potentiate drug-induced hearing loss.

Aminoglycoside antibiotics are essential for treating life-threatening bacterial infections, despite the risk of lifelong hearing loss. Infections induce inflammation and up-regulate expression of candidate aminoglycoside-permeant cation channels, including transient receptor potential vanilloid-1 (TRPV1). Heterologous expression of TRPV1 facilitated cellular uptake of (fluorescently tagged) gentamicin that was enhanced by agonists, and diminished by antagonists, of TRPV1.

Simplified, automated methods for assessing pixel intensities of fluorescently-tagged drugs in cells.

Assessing the cytoplasmic uptake of fluorescently-tagged drugs in heterogeneous cell types currently involves time-consuming manual segmentation of confocal microscopy images. We developed a set of methods that incorporate map algebra techniques to facilitate and expedite image segmentation, particularly of the parenchyma of intermediate cells in the stria vascularis of the inner ear. Map algebra is used to apply a convolution kernel to pixel neighborhoods to create a masking image to select pixels in the original image for further operations.