No abstract

<b><i>Objective:</i></b> Kidney stones are a common medical condition that is increasing in prevalence worldwide. Approximately, ∼80% of urinary calculi are composed of calcium oxalate (CaOx). There is a growing interest toward identifying therapeutic compounds that can inhibit the formation of CaOx crystals. However, some chemicals (e.g., antibiotics and bacterial metabolites) may directly promote crystallization. Current knowledge is limited regarding crystal promoters and inhibitors. Thus, we have developed an in vitro gel-based diffusion model to screen for substances that directly influence CaOx crystal formation. <b><i>Materials and Methods:</i></b> We used double diffusion of sodium oxalate and calcium chloride-loaded paper disks along an agar medium to facilitate the controlled formation of monohydrate and dihydrate CaOx crystals. A third disk was used for the perpendicular diffusion of a test substance to assess its influence on CaOx crystal formation. <b><i>Results:</i></b> We confirmed that citrates and magnesium are effective inhibitors of CaOx crystals. We also demonstrated that 2 strains of uropathogenic <i>Escherichia coli</i> are able to promote crystal formation. While the other tested uropathogens and most antibiotics did not change crystal formation, ampicillin was able to reduce crystallization. <b><i>Conclusion:</i></b> We have developed an inexpensive and high-throughput model to evaluate substances that influence CaOx crystallization.

investigation is required in order to confirm these results and delineate the potential mechanisms by which urinary pathogens and antibiotics may affect calcium-based stone formation.

RESULTS: DM tolerated 3 hours of constant CO2 anesthesia in combination with X-ray radiation exposure throughout the uCT acquisition, during which the optimal scanning protocol achieved DM survival and minimal image-noise. With this method, successful 3D reconstruction and visualization of DM adults were reproduced at 5.72 um isotropic voxel spacing, with stones clearly present (Fig.1). Analysis of the impact of BS168 on stone formation is ongoing. CONCLUSIONS: We have demonstrated that using CO2 gas during uCT imaging of live DM induces safe, repeatable, temporary fullbody immobilization without motion artefacts, for the purpose of visualizing stones. DM could fully recover after scans and we demonstrated the capability of this tool in time-course studies, as the same individuals were repeatedly scanned throughout the experiment. Currently this technique is being applied to characterize the effect of stone-modulating treatments such as probiotic bacteria with future potential in evaluating pharmaceuticals.