Bladder regeneration in a canine model using hyaluronic acid-poly(lactic-co-glycolic-acid) nanoparticle modified porcine small intestinal submucosa.

OBJECTIVE: • To determine if hyaluronic acid (HA) can be incorporated into porcine small intestinal submucosa (SIS) through poly (lactide-co-glycolide-acid) (PLGA) nanoparticles to improve the consistency of the naturally derived biomaterial and promote bladder tissue regeneration. METHODS: • Beagle dogs were subjected to 40% partial cystectomy followed by bladder augmentation with commercial SIS or HA-PLGA-modified SIS. • Urodynamic testing was performed before and after augmentation to assess bladder volume. • A scoring system was created to evaluate gross and histological presentations of regenerative bladders. RESULTS: • All dogs showed full-thickness bladder regeneration. • Histological assessment showed improved smooth muscle regeneration in the HA-PLGA-modified SIS group. • For both groups of dogs, urodynamics and graft measurements showed an approximate 40% reduction in bladder capacity and graft size from pre-augmentation to post-regeneration measurements. • Application of the scoring system and statistical analysis failed to show a significant difference between the groups. CONCLUSIONS: • SIS can be modified through the addition of HA-PLGA nanoparticles. The modified grafts showed evidence of improved smooth muscle regeneration on histological assessment, although this difference was not evident on a novel grading scale. • The volume loss and graft shrinkage experienced are consistent with previous models of SIS bladder regeneration at the 10-week time point. • Additional research into the delivery of HA and the long-term benefits of HA on bladder regeneration is needed to determine the full benefit of HA-PLGA-modified SIS. In addition, a more objective biochemical characterization will be needed to evaluate the quality of regeneration.

Restoring barrier function to acid damaged bladder by intravesical chondroitin sulfate.

PURPOSE: Chondroitin sulfate (Stellar Pharmaceuticals, London, Ontario, Canada), which is less expensive and more inert than heparinoids, hyaluronan or pentosan polysulfate, has been introduced to restore the barrier function lost due to epithelial dysfunction in interstitial cystitis cases. To our knowledge chondroitin sulfate binding to damaged bladder as a function of the urinary pH range, its efficacy in restoring the bladder permeability barrier and the capacity of the damaged bladder to bind chondroitin sulfate have not been determined previously. MATERIALS AND METHODS: Chondroitin sulfate binding to bladder urothelium was investigated quantitatively using chondroitin sulfate highly labeled with Texas Red(R) and quantitative fluorescence microscopy in a mouse model of urothelial acid damage. The efficacy of restoring barrier function was determined using the passage of intravesically instilled (86)Rb, a potassium ion mimetic, through the urothelium into the bloodstream in a rat model of bladder damage. The binding capacity of acid damaged bladder was determined by fluorometry. RESULTS: Chondroitin sulfate bound tightly and exclusively to the mouse bladder surface damaged by acid but showed only minimal binding to undamaged bladder. There was no systematic variation in pH. The model showed some variability in the degree of damage induced. In rats chondroitin sulfate instillation restored permeability to (86)Rb to control levels. Binding was saturable at a mean +/- SEM 0.67 +/- 0.13 mg/cm(2) of the bladder surface. CONCLUSIONS: Chondroitin sulfate binds preferentially to damaged urothelium and restores the impermeability barrier. This suggests that the glycosaminoglycan layer is a major contributor to bladder urothelial impermeability. As determined by binding capacity, the dose applied in humans in Canada (400 mg per instillation) is sufficient to achieve maximum efficacy.

Hydronephrosis in a woman undergoing in vitro fertilization.

Obstruction of a ureter secondary to tumor, fibrosis, or inflammation has been well documented in published reports. A review of English studies revealed no reported cases of hydronephrosis of a native kidney resulting from hyperstimulation of an ovary. We report a case of hydronephrosis in a woman undergoing ovarian stimulation for in vitro fertilization. Her presentation was prompted by symptoms of flank pain with nausea and vomiting. Management with ureteral stent placement was successful in relieving the obstructive symptoms. This case demonstrates the importance of imaging and close monitoring of symptoms in women undergoing in vitro fertilization.