Aims: The aims of the present study were to investigate voiding patterns, tissue constituents and the expressions of cyclooxygenase‐2 (COX‐2) and nitric oxide synthase (NOS) involved in ketamine‐induced ulcerative cystitis in rat urinary bladder.Methods: ThirtySprague–Dawleyrats were distributed into three groups which received saline or ketamine (25 mg/kg/day) for a period of 14 and 28 days. In each group, cystometry was performed weekly and the concentration of ketamine and its metabolites (norketamine) was assayed. Paraffin‐embedded sections were stained with Masson's trichrome stain, and ketamine‐induced morphological changes were examined. Western blot analyses were carried out to examine the expressions of COX‐2 and different NOS isoforms in bladder tissues. Immunofluorescence study was done to evaluate the expressions of COX‐2 and macrophage infiltration (stained with ED‐1 macrophage cell surface antigen) within the bladder.Results: Ketamine treatment resulted in bladder hyperactivity and the non‐voiding contractions were significantly increased. The urine concentrations of ketamine and norketamine were much higher in ketamine‐treated group. Moreover, ulcerated urothelium and mononuclear cell infiltration were noted in ketamine‐treated group. These alterations in urodynamic functions and tissue constituents were accompanied by increases in the expression of COX‐2. Two NOS isoforms (iNOS and eNOS) were also overexpressed, but no significant change was observed for nNOS. COX‐2 positive stained cells were significantly increased. Meanwhile, increased amounts of ED‐1 positive stained macrophages were present and most of COX‐2 expressed cells were co‐stained with ED‐1 in the early stage of ketamine treatment.Conclusions: Ketamine treatment affected bladder tissues by enhancing interstitial fibrosis and accelerating macrophages infiltration. Ketamine also initiated the up‐regulations of COX‐2 and iNOS and eNOS expressions. These up‐regulated enzymes might play an important role in contributing to ketamine‐induced alterations in micturition patterns and ulcerative cystitis.Neurourol. Urodynam. 32:1137–1143, 2013.

Overactive bladder (OAB) syndrome, including frequency, urgency, nocturia and urgency incontinence, has a significantly negative impact on the quality-of-life scale (QoL) and can cause sufferer withdrawal from social activities. The occurrence of OAB can result from an imbalance between the production of pro-oxidants, such as free radicals and reactive species, and their elimination through protective mechanisms of antioxidant-induced oxidative stress. Several animal models, such as bladder ischemia/reperfusion (I/R), partial bladder outlet obstruction (PBOO) and ovarian hormone deficiency (OHD), have suggested that cyclic I/R during the micturition cycle induces oxidative stress, leading to bladder denervation, bladder afferent pathway sensitization and overexpression of bladder-damaging molecules, and finally resulting in bladder hyperactivity. Based on the results of previous animal experiments, the present review specifically focuses on four issues: (1) oxidative stress and antioxidant defense system; (2) oxidative stress in OAB and biomarkers of OAB; (3) OAB animal model; (4) potential nature/plant antioxidant treatment strategies for urinary dysfunction with OAB. Moreover, we organized the relationships between urinary dysfunction and oxidative stress biomarkers in urine, blood and bladder tissue. Reviewed information also revealed the summary of research findings for the effects of various antioxidants for treatment strategies for OAB.

Ketamine abusers develop severe lower urinary tract symptoms. The major aims of the present study were to elucidate ketamine-induced ulcerative cystitis and bladder apoptosis in association with oxidative stress mediated by mitochondria and the endoplasmic reticulum (ER). Sprague-Dawley rats were distributed into three different groups, which received normal saline or ketamine for a period of 14 or 28 days, respectively. Double-labeled immunofluorescence experiments were performed to investigate tight junction proteins for urothelial barrier functions. A TUNEL assay was performed to evaluate the distribution of apoptotic cells. Western blot analysis was carried out to examine the expressions of urothelial tight junction proteins, ER stress markers, and apoptosis-associated proteins. Antioxidant enzymes, including SOD and catalase, were investigated by real-time PCR and immunofluorescence experiments. Ketamine-treated rats were found to display bladder hyperactivity. This bladder dysfunction was accompanied by disruptions of epithelial cadherin- and tight junction-associated proteins as well as increases in the expressions of apoptosis-associated proteins, which displayed features of mitochondria-dependent apoptotic signals and ER stress markers. Meanwhile, expressions of mitochondria respiratory subunit enzymes were significantly increased in ketamine-treated bladders. Conversely, mRNA expressions of the antioxidant enzymes Mn-SOD (SOD2), Cu/Zn-SOD (SOD1), and catalase were decreased after 28 days of ketamine treatment. These results demonstrate that ketamine enhanced the generation of oxidative stress mediated by mitochondria- and ER-dependent pathways and consequently contributed to bladder apoptosis and urothelial lining defects. Such oxidative stress-enhanced bladder cell apoptosis and urothelial barrier defects are potential factors that may play a crucial role in bladder overactivity and ulceration.

Numerous microorganisms residing in the gastrointestinal and genitourinary tracts affect host health. We investigated stool and voided urine samples collected from patients with benign prostatic hyperplasia (BPH) or prostate cancer (PC) and a control group to explore the potential relationship between human microbiota and prostatic disease, and aimed to identify correlations and pathogenic taxonomic units. We studied microbial composition using 16S rRNA sequencing to identify operational taxonomic units (OTUs). Extracted genome was amplified and filtered sequences were used to classify OTUs based on their specific taxonomy. No statistically significant differences were observed in stool samples among the groups. However, urine samples indicated different microbiota compositions in different patient populations. The top five microbial genera that showed significant differences between the BPH and control groups were Alcaligenes, Pseudomonas, Lactobacillus, Akkermansia, and Cetobacterium. Faecalibacterium, Staphylococcus, Ruminococcaceae_UCG_002, Neisseria, and Agathobacter were the genera with the largest proportion differences when comparing the PC and control groups. We discovered that the urine microbiota composition of the BPH and PC groups was distinct from that of the control group. Due to the impact of microbiota on prostatic disease, it is necessary to identify specific microbes for further research.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is defined as a chronic bladder disorder with suprapubic pain (pelvic pain) and pressure and/or discomfort related to bladder filling accompanied by lower urinary tract symptoms, such as urinary frequency and urgency without urinary tract infection (UTI) lasting for at least 6 weeks. IC/BPS presents significant bladder pain and frequency urgency symptoms with unknown etiology, and it is without a widely accepted standard in diagnosis. Patients’ pathological features through cystoscopy and histologic features of bladder biopsy determine the presence or absence of Hunner lesions. IC/PBS is categorized into Hunner (ulcerative) type IC/BPS (HIC/BPS) or non-Hunner (nonulcerative) type IC/BPS (NHIC/BPS). The pathophysiology of IC/BPS is composed of multiple possible factors, such as chronic inflammation, autoimmune disorders, neurogenic hyperactivity, urothelial defects, abnormal angiogenesis, oxidative stress, and exogenous urine substances, which play a crucial role in the pathophysiology of IC/BPS. Abnormal expressions of several urine and serum specimens, including growth factor, methylhistamine, glycoprotein, chemokine and cytokines, might be useful as biomarkers for IC/BPS diagnosis. Further studies to identify the key molecules in IC/BPS will help to improve the efficacy of treatment and identify biomarkers of the disease. In this review, we discuss the potential medical therapy and assessment of therapeutic outcome with urinary biomarkers for IC/BPS.

Background and Purpose: Shockwave lithotripsy (SWL) is a widely used treatment for patients with renal and ureteral stones because of its noninvasive approach. Although minor complications occur in most patients, a relative severe complication, perirenal or subcapsular hematoma, may also occur. We evaluate the possible risk factors for perirenal hematoma after SWL. Patients and Methods: Between 2001 and 2011, a total of 10,887 SWL treatments were performed for urolithiasis. All SWL procedures were performed using a Siemens Lithostar multiline lithotripter at a frequency of 2/sec under intermittent fluoroscopic guidance. All these patients underwent outpatient treatment without general anesthesia, but pethidine was administered for pain control. Treatment episodes were retrospectively reviewed for medical history, patient age, sex, body mass index (BMI), mean arterial pressure at induction, location of stone, total number of shockwaves, and peak shockwave intensity. We also compared the hematoma group with the control group (no hematoma formation after SWL with matched age and sex) for various factors. Results: After 10,887 treatment episodes on a total of 6177 patients during this period, subcapsular or perirenal hematoma developed in 20 patients for a total incident rate of 0.32%. Eighteen patients had the symptom of flank pain, and 2 patients received a diagnosis accidentally without symptoms. Four patients received a blood transfusion because of low hemoglobulin concentration. All of them received conservative and supportive treatment without surgical exploration. Ten (50%) patients had a history of hypertension. Renal hematoma developed in 11 patients at the second or third SWL treatment. Hypertension, higher BMI, and larger stone size are predisposing risk factors (P=0.022, 0.026 and 0.026, respectively) for renal hematoma. Conclusions: Renal hematoma is a rare (incidence rate, 0.32%) but possibly lethal complication. The most common symptoms of renal hematoma are severe flank pain and hematuria. A history of hypertension and higher BMI are important predisposing factors to perirenal hematoma.