The treatment of cataracts and glaucoma would require agents which are more permeable. In the context of the Q29X mutation that spares the cornea, the highly hydrophilic best structure of gentamicin limits its permeability through biological membranes, resulting in low ocular bioavailability and posing a pharmacokinetic limitation to the drug’s reaching therapeutic concentrations at the site of action in the eye. Although intraocular injections can theoretically deliver higher amounts of drug to potentially treat the glaucoma in a patient with the Q29X mutation and other intraocular diseases caused by missense mutations (15�C17, 52, 58, 65), compared with eye drop instillation, their administration is painful, requires a physician, and is associated with severe complications such as perforation of the globe and scarring of the conjunctiva.

In summary, our results demonstrate for the first time that a nonsense mutation in NBCe1-A known to cause proximal renal tubular acidosis can be corrected in vitro using the aminoglycoside G418. These results add to the compelling evidence that certain aminoglycoside structures can induce mammalian ribosomes to read-through PSC mutations and generate full-length functional proteins. The development of purmomycin analogs with improved read-through capability (45), and chemically unrelated compounds such PTC124 (62), suggests that the goal of developing clinically useful agents may be achievable in the not too distant future. GRANTS This work is supported by in part by National Institute of Diabetes and Digestive and Kidney Diseases Grants DK-077162, DK-07789, DK-058563, and DK-063125.

Notes The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked ��advertisement�� in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Footnotes 1The exact topology of NBCe1-A is currently unknown. The cotransporter has at least 10 transmembrane regions that have been documented (53). It is also possible that NBCe1-A has a topology that more closely resembles AE1, with 13 transmembrane regions and 2 reentrant loops (67).
Formalin fixed paraffin embedded (FFPE) tissues are a vast resource of clinically annotated samples with patient follow-up data.

As such, these samples represent highly desirable and informative materials for the application of high definition genomics that could improve patient management and provide a molecular basis for the selection of personalized therapeutics. The development of whole exome and whole genome technologies provides an unparalleled opportunity for advances Batimastat in improved treatment and diagnosis for patients with cancer [1], [2]. One major limitation to the use of routinely prepared FFPE tissues is the highly variable and typically poor quality of the DNA extracted from samples of interest [3]�C[6].