Therapeutic Effects of AF219 on Interstitial Cystitis/Bladder Pain Syndrome Induced by Cyclophosphamide or Water Avoidance Stress in Rats.

INTRODUCTION AND HYPOTHESIS: To evaluate the effect of AF219, a P2X3 receptor antagonist, in animal models of interstitial cystitis/bladder pain syndrome (IC/BPS) induced by cyclophosphamide (CYP) or water avoidance stress (WAS). METHODS: Thirty-two adult female Wistar albino rats were used in each IC/BPS model. Assessment of nociception and anxiety and severity of inflammation in the bladder were assessed by behavioral experiments and histopathological examinations respectively. The contraction responses of the bladder were evaluated in vitro and protein levels of P2X3, P2X7, Trk-A, TRPV1, and TRPA1 were analyzed by Western blot. RESULTS: The IC/BPS groups had shorter response times to noxious stimuli, exhibited more anxiety-like behavior, had higher inflammation-based histological scores, and showed greater increased contraction responses to carbachol, adenosine triphosphate, and electrical field stimulation in in vitro bladder strips than controls for both models (p < 0.05). The improvements in behavioral and bladder contraction responses and inflammation scores in the IC/BPS + AF219 groups were similar to control findings (p > 0.05). Exposure to WAS or CYP increased P2X3 expression in the bladder compared with the controls (p < 0.05). Apart from TRPA1, the levels of P2X7, Trk-A, and TRPV1 were also higher in the IC/BPS groups than in the controls (p < 0.05). No significant differences were observed between IC/BPS + AF219 and controls regarding P2X3, P2X7, Trk-A, and TRPV1 in the WAS model (p > 0.05). Moreover, P2X3 and P2X7 levels were significantly lower in IC/BPS + AF219 than in the AF219-untreated WAS model (p < 0.05). CONCLUSIONS: These findings suggest that P2X3 receptors play a significant role in bladder functional responses, nociception, and also the pathogenesis of IC/BPS. AF219 may be a promising therapeutic strategy for IC/BPS. Comparing AF219 with current IC/BPS treatment agents in future studies may yield valuable insights into its efficacy.

Factors predicting treatment success in mixed urinary incontinence treated with midurethral sling.

OBJECTIVES: We aimed to investigate success rates and predictive factors for midurethral slings (MUS) in women with mixed urinary incontinence (MUI). METHODS: Women with MUI (urodynamically diagnosed detrusor overactivity and stress urinary incontinence) treated with MUS between 2013 and 2020 were retrospectively investigated. Prior to MUS, all participants completed bladder diary and questionnaires and underwent a urodynamic study. Six months after surgery, patients were evaluated for lower urinary tract symptoms with pelvic examination, pad test, and the 8-item Overactive Bladder Questionnaire (OAB-V8) and the International Consultation on Incontinence Questionnaire-Short-Form (ICIQ-SF). Success rates after MUS were determined separately according to the predominant component of MUI. In addition, multivariable logistic regression analysis was used to determine the most important independent variables affecting the surgical outcome. RESULTS: There were 117 participants. The overall MUI cure rate was 73.5%, but surgical success in the presence of postoperative urgency was 60.7%. Moreover, MUS success rate was 84.8% in those with preoperative stress-dominant MUI. However, the success rates for equally and urgency-dominant MUI were both 29.4%. Preoperative OAB-V8 score, symptom duration >9.5 years, and preoperative anticholinergic medication were risk factors for persistent urgency and urgency urinary incontinence (UUI) postoperatively (p < .05). In addition, diabetes mellitus (DM) for persistent urgency and voiding frequency (daily) for persistent UUI were predictive factors (p < .05). CONCLUSIONS: MUS may be offered to women with stress-dominant MUI. However, postoperative urgency might change a patient's perception of treatment despite successful incontinence treatment. MUS does not appear to be a good option when MUI patients have a high OAB-V8 score, symptom duration >9.5 years, DM, or use of anticholinergic medication preoperatively.

Urinary nerve growth factor and a variable solifenacin dosage in patients with an overactive bladder.

INTRODUCTION AND HYPOTHESIS: We evaluated changes in urinary nerve growth factor (NGF) and NGF/creatinine (NGF/Cr) levels after increasing the dosage of solifenacin in overactive bladder patients. METHODS: The study groups included 59 overactive bladder (OAB) patients and 20 healthy subjects as controls. We measured NGF at baseline for the patients and controls, and used the Overactive Bladder Awareness Tool (OAB-V8) to evaluate urinary symptoms. All patients received a treatment of solifenacin 5 mg for 6 weeks. The responders to treatment served as group 1 and nonresponders received solifenacin 10 mg for an additional 6 weeks. Responders and nonresponders to the 10-mg treatment were defined as groups 2 and 3 respectively. NGF was measured after each treatment using the ELISA method and normalized by the urinary creatinine levels (NGF/Cr). RESULTS: There were 21, 22 and 16 patients in groups 1, 2, and 3 respectively. At baseline, the NGF and NGF/Cr levels were higher in groups 1, 2, and 3 compared with the controls. After the solifenacin 5 mg treatment, the NGF and NGF/Cr levels of group 1 individuals decreased to those of the control level. After increasing the dosage of solifenacin to 10 mg in group 2, the NGF and NGF/Cr levels decreased to normal levels. In group 3 (patients who did not responded to any treatment), these levels remained unchanged. CONCLUSIONS: Our results suggest that urinary NGF could be a potential biomarker for monitoring the treatment of symptoms in OAB patients who are treated with solifenacin.

Intravesical Migration of Missed Intrauterine Device Associated with Stone Formation: A Case Report and Review of the Literature.

Intrauterine device is the most widely used method of reversible contraception. It may cause various complications including perforation of uterus. In this case, 44-year-old woman was presented with lower urinary tract symptoms after six years of insertion. Patient has no remarkable physical or laboratory finding but abdominal ultrasound revealed a 27 mm hyperechogenicity, suggestive of foreign body or calculus on the posterior bladder wall which was removed endoscopically. This case highlights the need of immediate and periodic evaluation of women with intrauterine device to avoid missing serious complications.

Comparison of transobturator tape surgery using commercial and hand made slings in women with stress urinary incontinence.

PURPOSE: To compare the complications and success rates of hand-made sling with commercial sling used in transobturator tape (TOT) surgery. MATERIALS AND METHODS: From 2008 to 2010, hand-made slings were used in TOT surgery, whereas commercial slings were used from 2010 to 2013 in our clinic. Overall 102 patients were included in the study. Patients were categorized into 2 groups: group 1 had hand-made (polypropylene monofilament) slings, while group 2 had commercial slings (polypropylene monofilament). We retrospectively reviewed 1-year follow-up results of the whole cohort. Ages, body mass indexes, menopausal status, operation time, cost of sling, success of operation and complications were recorded. All these data were compared between the 2 groups. RESULTS: There were 41 patients (54.29 ± 9.88 years) in group 1 and 61 patients (52.82 ± 9.85 years) in group 2. Menopausal status and body mass index (28.1 vs. 29.2 kg/m² respectively) were similar for both groups. Previous history of incontinence or pelvic organ prolapse surgery (P = .046), mean duration of the procedure (P = .001), and vaginal extrusion rate (P = .016) were significantly lower in group 2. The cost of the sling was higher in group 2 than in group 1. There was no significant difference in success of operation between the groups (P = .319). CONCLUSION: According to our results, hand-made mesh is a viable option in TOT surgery with similar efficacy, but surgeons should be careful in terms of vaginal extrusion.

Angioleiomyoma of the scrotal wall.

Angioleiomyoma of the scrotum is a rare benign lesion which can mimic a paratesticular tumor. Any solid mass within the scrotum is considered malignant until proven otherwise. Here, we present a case of an angioleiomyoma of the scrotum in a 33-year-old male who presented with painful scrotal mass. Scrotal ultrasonography demonstrated a solid mass in the scrotum, and surgical excision was carried out. Pathologic examination revealed that the tumor was angioleiomyoma.

A new technique--"lipocorticoplasty"--for the closure of partial nephrectomy defects and its comparison with the standard technique.

OBJECTIVE: We describe a new technique that can easily be used as a tension-free practical alternative in closing the renal defects resulting after open partial nephrectomy (PN). METHODS: A new technique (called "lipocorticoplasty") where "wrapped fatty tissue" was placed in the tumor crater to close the renal defects that occur following PN is reported in 10 consecutive patients who underwent PN between May 2006 and January 2009 (Group I). Patients were compared with equal number of consecutive patients who underwent standard open PN before January 2009 (Group II) in terms of operative time, bleeding, tumor size, drain removal time, postoperative length of stay (PLOS), complications, and functional and oncological follow-up. Postoperative follow-up included physical examination, laboratory tests, and radiological screening at 3-month intervals for the first year, at 6-month intervals for the second year, and annually thereafter. RESULTS: Mean tumor size (35.2 vs. 33.8 mm), operative time (156 vs. 165 min), bleeding (650 vs. 765 cc), drain removal time (2.8 vs. 2.5 POD), and PLOS (4.4 vs. 4.2 POD) were not statistically different between Group I and Group II, respectively. No intraoperative complications occurred. Postoperatively, transient complications without any permanent sequela were observed in 3 (1 in Group I and 2 in Group II) patients. Mean follow-up time was 16.1 months (7-26) in Group I and 19.1 months (8-36) in Group II. None of the patients had local or systemic recurrence at follow-up. CONCLUSION: Our new technique provides obvious benefits in local hemostasis, simplifies parenchymal suturing, obviates the need for coaptation of the edges of the tumor bed defect under tension, and minimizes nephron loss due to kinking and tearing of renal parenchyma in the closure of the renal defects following open renal tumor excision.

Protective effects of pentoxifylline on cigarette smoking-induced renal tissue damage in rats.

In this study, we investigated the protective effect of pentoxifilline (PTX) on smoking-induced damage in rat kidney tissues. Twenty-seven male Wistar rats were used in the study. Animals were divided into three equal groups as follows: Group 1: control group with only normal saline (NS; 0.9% NaCl) injection for 8 weeks; Group 2: cigarette smoking and NS injection for 8 weeks; and Group 3: cigarette smoking and PTX injection for 8 weeks. The rats were sacrificed after 8 weeks and their kidneys were excised for histopathological analysis. Serial paraffin sections (5 µm) of the kidneys were cut and stained with hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS). The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) method was used to assess apoptosis. Glomerular diameters, glomerular cell number and proximal tubule cell numbers were compared between the groups. Our results showed that PTX treatment prevented negative effects of smoking in rat kidneys. There was a statistically significant difference in all assessed parameters between Group 2 and other groups (p < 0.05). In conclusion, our study shows that PTX treatment is effective in preventing the negative effects of cigarette smoking on kidneys by inhibiting cell damage with its antioxidant properties.

Effects of lumbar lordosis and pelvic inlet orientation on the outcome of the transobturator tape sling operation in women.

PURPOSE: To determine the association between changes in lumbar lordosis (LL) and/or pelvic inlet (PI) orientation and the outcome of a transobturator tape (TOT) sling procedure. METHODS: The study population consisted of 70 patients who underwent the TOT sling procedure for stress urinary incontinence, and were evaluated by a stress test at the sixth month after the surgery. The women were defined as continent on the absence of both subjective complaint of leakage and objective leakage as a result of the test. Cases that failed, even though improvement may have been observed, were considered incontinent. With the use of a standardized protocol, lateral lumbosacral spine/pelvic X-rays were taken with the participants standing in their usual upright posture with hands kept at chest level. From these X-rays, the angle of LL and PI were measured. RESULTS: Of the 70 cases, 42 were continent and 28 were incontinent according to the evaluation done during the sixth month after the TOT procedure. There were no significant differences with respect to age, body mass index, gravidity, vaginal parity, pelvic organ prolapse and comorbid diseases between the continent and incontinent groups. The mean angle of PI in the continent group (34°, range 20-50) was significantly lower than in the incontinent group (37°, range 28-60) (p = 0.012). There was no significant difference in the median angle of LL (32°, range 15-50 in continent group, 34.5°, range 21-56 in incontinent group, p = 0.13) between the two groups. CONCLUSIONS: Women with continence after the TOT sling procedure have lower angle of PI than women with incontinence.

Effects of anesthetics on cystometric parameters in female rats.

AIM: The purpose of this study was to evaluate the effect of ketamine, propofol, midazolam and ether on cystometric parameters in rats. METHODS: Thirty adult female Wistar rats were divided into four groups according to the agent used for the anesthesia; group 1: ether inhalation, group 2: midazolam, group 3: propofol and group 4: ketamine. After surgical implantation of catheter, cystometry was performed in awake rats followed by same procedure under anesthesia. Immediately following awake cystometry, six rats were anesthetized with midazolam (25 mg/kg) intraperitoneally (i.p.), seven rats were anesthetized with propofol (20 mg/kg) i.p., and 11 rats were anesthetized with ketamine (15 mg/kg) i.p. In other six rats, ether inhalation anesthesia was used after awake cystometry. Cystometric parameters such as resting bladder pressure, micturition pressure and the period between micturition were analyzed with Wilcoxon signed-rank test for statistical analysis. RESULTS: There was no statistically significant effect of ether and midazolam on cystometric parameters, compared to awake rats. Propofol was found to change all measured cystometric parameters without statistically significant difference. The period between micturition was clearly prolonged by propofol but it was also not statistically significant. Ketamine was found to be very depressant on micturition. CONCLUSION: The results suggest that ether and midazolam are preferable to ketamine for anesthetized cystometry studies. The results were questionable for propofol, and further studies are needed to make it clear.

Effect of memantine on overactive detrusor in rats with spinal cord injury.

The aim of this study was to determine the effect of memantine on overactive detrusor (OAD) 15 days after spinal cord injury (SCI) in rats. Twenty-eight adult Wistar rats were used in this study. Fourteen animals served as normal controls, while 14 underwent spinal cord transection (clip compression technique) at the 10th thoracic vertebra. Fifteen days after SCI, all animals underwent urodynamic testing to confirm OAD. Memantine (16 mg/kg) was injected intraperitoneally into rats with SCI and OAD. Parameters measured included voiding volume, micturition pressure, resting bladder pressure, the period between micturitions and the maximum pressure of the OAD during the filling period. Results have showed that OAD developed in 8/14 animals (57.1%). OAD was resolved in 5/8 (62.5%) of these animals after memantine administration. Resting bladder pressure was significantly different in dependent groups (p < 0.05). Micturition pressure increased after SCI but decreased in rats with SCI after memantine injection. However, the period between micturitions was prolonged in both SCI and memantine groups, compared with normal rats. These results show that memantine could be useful for treating neurogenic OAD after SCI by modulating the micturition reflex pathway. Memantine may also provide an alternative treatment option for OAD in the future.

The effect of asymptomatic urethral caruncle on micturition in women with urinary incontinence.

PURPOSE: The aim of this study was to evaluate the effect of asymptomatic urethral caruncle (UC) on micturition in women suffering from urinary incontinence. MATERIALS AND METHODS: A total of 232 patients participated in the study. UC was diagnosed in 50 of 232 patients with urinary incontinence during a physical examination in our clinic. All cases were divided into 2 groups: UC combined with urinary incontinence (group 1) and urinary incontinence only (group 2). Urodynamic evaluations were performed according to the International Continence Society standards. RESULTS: Both groups were similar in terms of voiding diary, pad test and residual urine volume. Urodynamic studies revealed no significant difference between group 1 and 2 (infravesical obstruction: 6% vs. 4.4%; overactive detrusor: 44% vs. 42.9% respectively). The rates of severe IPSS (37.8% vs. 20.9%) and severe cystocele (20.9% vs. 13.8%) were numerically higher in group 1 with no statistically significant difference. CONCLUSIONS: Our results suggest that there is no effect of asymptomatic UC on lower urinary tract symptoms in women with urinary incontinence. Therefore, treating asymptomatic UC is unnecessary in these patients. However, during incontinence surgery, it is the surgeon's decision whether to treat asymptomatic UC.

First report of overactive detrusor in association with hypospadias detected by urodynamic screening.

AIMS: The purpose of this study was to determine urodynamic features in hypospadic patients. METHODS: Thirty-seven patients with hypospadias (distal: 31, proximal: 6) underwent preoperative urodynamic study according to International Continence Society (ICS) recommendations. Statistical analysis were done for comparison between urethral obstruction and non-obstruction in patients with detrusor overactivity (DO) plus the relationship of DO with localization of hipospadias. RESULTS: Nearly 45.9% of the patients showed overactive detrusor. Urethral obstruction was found in 60.8% of the patients. The rate of DO was higher in proximal hipospadias, and urethral obstruction than distal type, and non-obstructed patients (P > 0.005). The means overall cystometric capacity, maximum voiding detrusor pressure and maximal urinary flow measured were 132.6 +/- 111.14 ml (range 21-610), 72 +/- 53 cmH2O (range 12-181), and 7.9 +/- 7.1 ml/sec (range 2-30 ml/sec), respectively. CONCLUSIONS: To the best of our knowledge, this is the first study ever to show that overactive detrusor is an accompanying entity in the hypospadic patients.