title: Characterization and optimization of experimental variables within a reproducible bladder encrustation model and in vitro evaluation of the efficacy of urease inhibitors for the prevention of medical device-related encrustation.
abstract: This study presents a reproducible, cost-effective in vitro encrustation model and, furthermore, describes the effects of components of the artificial urine and the presence of agents that modify the action of urease on encrustation on commercially available ureteral stents. The encrustation model involved the use of small-volume reactors (700 mL) containing artificial urine and employing an orbital incubator (at 37 degrees C) to ensure controlled stirring. The artificial urine contained sources of calcium and magnesium (both as chlorides), albumin and urease. Alteration of the ratio (% w/w) of calcium salt to magnesium salt affected the mass of encrustation, with the greatest encrustation noted whenever magnesium was excluded from the artificial urine. Increasing the concentration of albumin, designed to mimic the presence of protein in urine, significantly decreased the mass of both calcium and magnesium encrustation until a plateau was observed. Finally, exclusion of urease from the artificial urine significantly reduced encrustation due to the indirect effects of this enzyme on pH. Inclusion of the urease inhibitor, acetohydroxamic acid, or urease substrates (methylurea or ethylurea) into the artificial medium markedly reduced encrustation on ureteral stents. In conclusion, this study has described the design of a reproducible, cost-effective in vitro encrustation model. Encrustation was markedly reduced on biomaterials by the inclusion of agents that modify the action of urease. These agents may, therefore, offer a novel clinical approach to the control of encrustation on urological medical devices.
authors.affiliation: School of Pharmacy, The Queen's University of Belfast, Medical Biology Centre, Belfast BT9 7BL, Northern Ireland, UK. d.jones@qub.ac.uk
authors.forename: David S
authors.initials: DS
authors.lastname: Jones
authors.forename: Jasmina
authors.initials: J
authors.lastname: Djokic
authors.forename: Sean P
authors.initials: SP
authors.lastname: Gorman
mesh_terms: D000418:Albumins; D003362:Cost-Benefit Analysis; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D004864:Equipment and Supplies / Q000009:adverse effects*; D006801:Humans; D015203:Reproducibility of Results; D013054:Spectrophotometry, Atomic; D015607:Stents; D014510:Urease / Q000037:antagonists & inhibitors*; D001745:Urinary Bladder Diseases / Q000517:prevention & control*; D014556:Urine
chemical_list: D000418:Albumins; D004791:Enzyme Inhibitors; D014510:Urease