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Modeling drug dispersion in the inner ear fluids: The importance of accurate 3D anatomi- cal studies. (Abstract of ARO Meeting Denver, Colorado) Alec N. Salt1, Timothy A. Holden1, Ruth M. Gill1, Stefan K. Plontke2 1Washington University School of Medicine, 2University of Tubingen

Locally-applied drugs are increasingly being used for the clinical treatment of inner ear disorders such as Meniere‘s disease, sudden hearing loss and tinnitus. Knowledge of the dosages achieved and where in the ear the drugs reach is essential to optimize therapies. In animals, experimental studies have shown that drug spread in the inner ear is dominated by diffusion that takes place slowly along the fluid spaces. Quantitative interpretation of experimental measurements and prediction of the likely drug distribution in humans is only possible through quantitative computer models. Whether the model is a simple 1D representation of a scala or a sophisticated 3D representation of the inner ear, the calculations are highly dependent on the dimensions of the compartments that are used. With more sophisticated models, the interactions of each compartment with adjacent structures also need to be incorporated. At present, models are restricted by the limited availability of anatomic descriptions of the ear. Quantitative anatomic studies have become more feasible with the increased availability of 3D reconstruction programs and the increased capabilities of desktop computers. Data sets for analysis can be obtained from serial histo- logical sections, magnetic resonance microscopy (MRM), computed tomography (CT) and orthogonal plane fluorescence optical sectioning (OPFOS). Each of these methods has different capabilities in terms of which tissues can be detected and at what resolution. As the voxel resolution of the methods increa- ses, the effort required to segment structures increases dramatically, limiting the number of specimens that can be analyzed. Other limitations arise from tissue shrinkage and long preparation times. In some applications, combining structures segmented from different data sets, such as bone from a CT scan and soft tissues from an OPFOS scan can aid the analysis. The long-term goal of this work is to develop a 3D model of the ear, through which drug dispersal can be calculated based on the anatomic communica- tions present and incorporating the transport and permeability properties of tissue boundaries (Suppor- ted by NIH/NIDCD grants DC01368 (AS) and DC000581 (TH) and BMBF grant 0313844b (SP)).

A pilot clinical trial of the effects of coenzyme Q10 on chronic tinnitus aurium. Otolaryngol Head Neck Surg. 2007 Jan;136(1):72-77 Khan M, Gross J, Haupt H, Jainz A, Niklowitz P, Scherer H, Schmidt FP, Klapp BF, Reisshauer A, Mazurek B Department of Otorhinolaryngology, Charite-University Medicine Berlin, Berlin, Germany.

Objective: To determine the short-term effects of coenzyme Q10 (CoQ10) on the antioxidative status and tinnitus expression in patients with chronic tinnitus aurium. Study Design: A 16-week prospective nonrandomized clinical trial (n = 20). Tinnitus and Short Form-36 Questionnaires (TQ/SF-36) were evaluated together with the plasma concentrations of CoQ10, malondi- aldehyde, and the total antioxidant status. Results: The mean plasma CoQ10 concentration rose under external CoQ10 supply and remained ele- vated after medication stopped without overall effects on the tinnitus score. However, in a subgroup of 7 patients with low initial plasma CoQ10 concentration and significant increase in the plasma CoQ10 level, a clear decrease in the TQ score was observed. Conclusion: In patients with a low plasma CoQ10 concentration, CoQ10 supply may decrease the tinni- tus expression. Significance: This is the first study to examine the effect of CoQ10 in chronic tinnitus aurium.

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