Search

Objectives To identify and characterise urinary cationic metabolites, defined as toxic factors, in patients with interstitial cystitis ( IC) and in control subjects. To evaluate the cytotoxicity of the urinary cationic metabolite fraction of patients with IC vs control subjects and of individual metabolites in cultured urothelial cells. Subjects and Methods Cationic fractions ( CFs) were isolated from the urine specimens of 62 patients with IC and 33 control subjects by solid-phase extraction. CF metabolites were profiled using C18 reverse-phase high performance liquid chromatography ( RP-HPLC) with UV detection, quantified by area-under-the-peaks using known standards, and normalized to creatinine. RP-HPLC and liquid chromatography ( LC)-mass spectrometry ( MS)/tandem MS ( MS/ MS) were used to identify major CF peaks. HTB-4 urothelial cells were used to determine the cytotoxicity of CFs and of individual metabolites with and without Tamm- Horsfall protein ( THP). Results RP-HPLC analysis showed that metabolite quantity was twofold higher in patients with IC compared with control subjects. The mean ( sem) for control subjects vs patients was 3.1 (0.2) vs 6.3 (0.5) mAU*min/μg creatinine ( P < 0.001). LC-MS identified 20 metabolites. Patients with IC had higher levels of modified nucleosides, amino acids and tryptophan derivatives compared with control subjects. The CF cytotoxicity was higher for patients with IC compared with control subjects. The mean ( sem) for control subjects vs patients was −2.3 (2.0)% vs 36.7 (2.7)% ( P < 0.001). A total of 17 individual metabolites were tested for their cytotoxicity. Cytotoxicity data for major metabolites were all significant ( P < 0.001): 1-methyladenosine (51%), 5-methylcytidine (36%), 1-methyl guanine (31%), N4-acetylcytidine (24%), N7-methylguanosine (20%) and L- Tryptophan (16%). These metabolites were responsible for higher toxicity in patients with IC. The toxicity of all metabolites was significantly lower in the presence of control THP ( P < 0.001). Conclusions Major urinary cationic metabolites were characterised and found to be present in higher amounts in patients with IC compared with control subjects. The cytotoxicity of cationic metabolites in patients with IC was significantly higher than in control subjects, and control THP effectively lowered the cytotoxicity of these metabolites. These data provide new insights into toxic factor composition as well as a framework in which to develop new therapeutic strategies to sequester their harmful activity, which may help relieve the bladder symptoms associated with IC. [ABSTRACT FROM AUTHOR]

To determine whether men previously diagnosed with prostatitis also have pathology originating in the bladder.We administered the pelvic pain and urgency/frequency (PUF) questionnaire and the potassium-sensitivity test (PST) to 50 patients with prostatitis presenting in urological and primary care, and to 14 controls. In a separate control group of 22 men, the urethra was irrigated with KCl or NaCl (11 each) before and after experimental injury of the urethral mucosa.All 50 patients with prostatitis had PUF scores of≥ 7; 77% were positive for the PST. All 14 controls had PUF scores of 1 or 0 and a negative PST. In the urethral irrigation study in controls, KCl but not NaCl provoked urethral pain after mucosal injury. Before injury, neither KCl nor NaCl caused symptoms.The high rate of positive PST in patients with‘classic’ prostatitis indicates that pathology originating in the bladder may be an important source of symptoms in most. In patients with prostatitis and female patients with interstitial cystitis, symptoms may arise not from separate disease entities but from a continuum of epithelial dysfunction and potassium cycling that may be present throughout the lower urinary tract. [ABSTRACT FROM AUTHOR]