Correlation of gene expression with bladder capacity in interstitial cystitis/bladder pain syndrome.

PURPOSE: Interstitial cystitis and bladder pain syndrome are terms used to describe a heterogeneous chronic pelvic and bladder pain disorder. Despite its significant prevalence, our understanding of disease etiology is poor. We molecularly characterized interstitial cystitis/bladder pain syndrome and determined whether there are clinical factors that correlate with gene expression. MATERIALS AND METHODS: Bladder biopsies from female subjects with interstitial cystitis/bladder pain syndrome and female controls without signs of the disease were collected and divided into those with normal and low anesthetized bladder capacity, respectively. Samples then underwent RNA extraction and microarray assay. Data generated by these assays were analyzed using Omics Explorer (Qlucore, Lund, Sweden), GeneSifter® Analysis Edition 4.0 and Ingenuity® Pathway Analysis to determine similarity among samples within and between groups, and measure differentially expressed transcripts unique to each phenotype. RESULTS: A total of 16 subjects were included in study. Principal component analysis and unsupervised hierarchical clustering showed clear separation between gene expression in tissues from subjects with low compared to normal bladder capacity. Gene expression in tissue from patients with interstitial cystitis/bladder pain syndrome who had normal bladder capacity did not significantly differ from that in controls without interstitial cystitis/bladder pain syndrome. Pairwise analysis revealed that pathways related to inflammatory and immune response were most involved. CONCLUSIONS: Microarray analysis provides insight into the potential pathological condition underlying interstitial cystitis/bladder pain syndrome. This pilot study shows that patients with this disorder who have low compared to normal bladder capacity have significantly different molecular characteristics, which may reflect a difference in disease pathophysiology.

Prophylactic effect of tadalafil on bladder function in a rat model of chronic bladder ischemia.

PURPOSE: We investigated the effect of tadalafil on chronic ischemia related bladder dysfunction. MATERIALS AND METHODS: Adult male Sprague-Dawley® rats were divided into control, arterial endothelial injury and arterial endothelial injury with tadalafil treatment groups. The arterial injury and arterial injury-tadalafil groups underwent endothelial injury of the iliac arteries and received a 2% cholesterol diet after injury. Arterial injury-tadalafil rats received tadalafil (2 mg/kg per day) orally for 8 weeks after injury. The control group received a regular diet. At 8 weeks urodynamic investigation was performed. Bladder tissue was harvested for pharmacological studies, and histological examination of the iliac arteries and bladders was performed. RESULTS: Iliac arteries from arterial injury and arterial injury-tadalafil rats showed neointimal formation and luminal occlusion. In the arterial injury group the micturition interval was significantly shorter (mean ± SEM 5.4 ± 0.5 vs 11.1 ± 1.1 minutes), and bladder capacity and voided volume were less than in controls. Contractile responses of bladder strips to KCl, electrical field stimulation and carbachol were significantly less after arterial injury than in controls. The arterial injury group showed a significantly increased percent of collagen compared with controls (mean 37.4% ± 1.8% vs 21.5% ± 1.8%). In the arterial injury-tadalafil group intimal formation and luminal occlusion were not prevented. However, there were significant improvements in all functional and morphological parameters compared with the arterial injury group. CONCLUSIONS: Arterial occlusive disease may lead to chronic bladder ischemia and bladder hyperactivity. Chronic treatment with tadalafil protects bladder function and morphology, resulting in decreased bladder hyperactivity. If valid for humans, the data support phosphodiesterase 5 inhibition as treatment for chronic ischemia related bladder dysfunction.

Halofuginone infused keratin hydrogel attenuates adhesions in a rodent cecal abrasion model.

BACKGROUND: Postoperative adhesion formation continues to be a significant surgical complication, and methods for preventing abdominopelvic adhesions remain limited. Halofuginone (HF) is a type-1 collagen synthesis inhibitor and may enhance the effects of a physical barrier in preventing adhesion formation. We evaluated the effectiveness of a HF infused keratin hydrogel on preventing adhesions in a rat cecal abrasion model. MATERIAL AND METHODS: Laparotomy and standardized cecal abrasion was performed on 58 retired-breeder Sprague Dawley female rats to induce intra-abdominal adhesions. Rats were randomized to: no treatment; Interceed absorbable adhesion barrier; keratin hydrogel alone; or keratin hydrogel infused with 22 µg/mL of HF. Necropsies were performed at postop d-14 to assess the extent and tenacity of adhesions and grade histologic inflammation and fibrosis using a standard scoring system. Serum, liver, kidneys, and lungs were harvested to evaluate tissue HF concentrations. Protein and drug elution curves were generated to assess the release of HF from the hydrogel. RESULTS: Treatment with Keratin-HF hydrogel resulted in significantly fewer abdominal adhesions than any other treatment, and significantly less dense adhesions compared with Interceed or keratin hydrogel alone. Subset histologic analysis did not reveal qualitative differences. HF was undetectable in serum and kidneys, and detected at negligible concentrations in liver and lungs. Keratin-HF hydrogel drug release in phosphate-buffered solution (PBS) was sustained over 7 d and correlated with keratin protein degradation. CONCLUSIONS: Keratin-HF hydrogel is a novel therapeutic agent that may provide a better method for preventing the development of postoperative adhesions using a combined physical barrier and pharmacologic approached.

Transcriptome analysis of bladder biopsy from interstitial cystitis/bladder pain syndrome patients.

Interstitial cystitis and bladder pain syndrome (IC/BPS) are terms used to describe a heterogeneous chronic pelvic and bladder pain disorder. Despite its significant prevalence, the disease etiology is not well understood and providing diagnosis and treatment can be challenging. In our study, published recently in the Journal of Urology (Colaco et al., 2014), we describe the use of microarrays as a tool to characterize IC/BPS and to determine if there are clinical factors that correlate with gene expression. This data-in-brief article describes the methodology for that study, including data analysis, in further detail. Deposited data can be found in the Gene Expression Omnibus (GEO) database: GSE57560.

Synthetic mesh in the surgical repair of pelvic organ prolapse: current status and future directions.

In light of the recent Food and Drug Administration public health notification regarding complications associated with transvaginally placed mesh for pelvic organ prolapse (POP) repair, we review recent literature to evaluate current outcomes and complication data, analyze the clinical need for mesh on the basis of genetic and biochemical etiologies of POP, and investigate trends of mesh use via an American Urological Association member survey. Mesh-based techniques show better anatomic results than traditional repair of anterior POP, but subjective outcomes are equivalent. Further research and Level I evidence are required before mesh-based repair of POP can be standardized. Adequate surgical training and patient selection should decrease complication rates.

Impact of stone removal on renal function: a review.

Stone removal can improve renal function by eradicating obstruction and, in certain cases, an underlying infection. Stone-removing procedures, however, may negatively impact functional integrity. Many things may impact the latter, including the procedures used, the methods of assessing function, the time when these assessments are made, the occurrence of complications, the baseline condition of the kidney, and patient-related factors. In the majority of cases, little significant functional impairment occurs. However, there are gaps in our knowledge of this subject, including the cumulative effects of multiple procedures violating the renal parenchyma and long-term functional outcomes.