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Micro/Nano plastics (MNPs) pollutants are widespread in the environment, raising significant concerns about their biosafety. Emerging studies indicate that the urinary system is a primary accumulation site for MNPs, leading to severe tissue and functional damage. This review aims to summarize recent research on the potential hazards that MNPs may pose to the urinary system, highlighting the mechanisms of toxicity and the current state of knowledge. Studies have shown that MNPs enter the human body through drinking water, the food chain, inhalation, and skin contact. They may penetrate the bloodstream via the digestive, respiratory, and skin systems, subsequently dispersing to various organs, including the urinary system. The potential accumulation of MNPs in the urinary system might induce cellular oxidative stress, inflammation, apoptosis, autophagy, the "intestine-kidney axis", and other possible toxic mechanisms. These processes could disrupt kidney metabolic functions and promote tissue fibrosis, thereby potentially increasing the risk of urinary system diseases. Despite ongoing research, the understanding of MNPs' impact on the urinary system remains limited. Therefore, this review provides a comprehensive overview of MNPs' potential toxicity mechanisms in the urinary system, highlights key challenges, and outlines future research directions. It offers a theoretical basis for the development of effective protective measures and policies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Upper tract urothelial carcinomas (UTUCs) are rare entities that are usually diagnosed at advanced stages. Research on UTUC pathobiology and clinical management has been hampered by the lack of models accurately reflecting disease nature and diversity. In this study, a modified organoid culture system is used to generate a library of 25 patient-derived UTUC organoid lines retaining the histological architectures, marker gene expressions, genomic landscapes, and gene expression profiles of their parental tumors. The study demonstrates that the responses of UTUC organoids to anticancer drugs can be identified and the model supports the exploration of novel treatment strategies. This work proposes a modified protocol for generating patient-derived UTUC organoid lines that may help elucidate UTUC pathophysiology and assess the responses of these diseases to various drug therapies in personalized medicine., (© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Nowadays, caffeine is one of the most commonly consumed substances, which presents in many plants and products. It has both positive and negative effects on the human body, and its activity concerns a variety of systems including the central nervous system, immune system, digestive system, respiratory system, urinary tract, etc. These effects are dependent on quantity, the type of product in which caffeine is contained, and also on the individual differences among people (sex, age, diet etc.). The main aim of this review was to collect, present, and analyze the available information including the latest discoveries on the impact of caffeine on human health and the functioning of human body systems, taking into account the role of caffeine in individual disease entities. We present both the positive and negative sides of caffeine consumption and the healing properties of this purine alkaloid in diseases such as asthma, Parkinson's disease, and others, not forgetting about the negative effects of excess caffeine (e.g., in people with hypertension, children, adolescents, and the elderly). In summary, we can conclude, however, that caffeine has a multi-directional influence on various organs of the human body, and because of its anti-oxidative properties, it was, and still is, an interesting topic for research studies including those aimed at developing new therapeutic strategies.

This review paper deals with the influence of androgens (testosterone) on pelvic autonomic pathways in male mammals. The vast majority of the relevant information has been gained in experiments involving castration (testosterone deprivation) performed in male rats, and recently, in male pigs. In both species, testosterone significantly affects the biology of the pathway components, including the pelvic neurons. However, there are great differences between rats and pigs in this respect. The most significant alteration is that testosterone deprivation accomplished a few days after birth results some months later in the excessive loss (approximately 90%) of pelvic and urinary bladder trigone intramural neurons in the male pig, while no changes in the number of pelvic neurons are observed in male rats (rats do not have the intramural ganglia). In the castrated pigs, much greater numbers of pelvic neurons than in the non-castrated animals express CGRP, GAL, VIP (peptides known to have neuroprotective properties), and caspase 3, suggesting that neurons die due to apoptosis triggered by androgen deprivation. In contrast, only some morpho-electrophysiological changes affecting neurons following castration are found in male rats. Certain clinicopathological consequences of testosterone deprivation for the functioning of urogenital organs are also discussed.

Purpose: To evaluate the pharmacokinetic properties of UGN-101, a mitomycin-containing reverse thermal gel used as primary chemoablative treatment for low-grade upper tract urothelial carcinoma (UTUC), in a subset of patients participating in a phase 3 clinical trial., Methods: Pharmacokinetic parameters (C max , T max , AUC (0-6) , λz, t ½ , and AUC inf ) were evaluated in six participants (male or female, ≥ 18 years) with biopsy-proven, low-grade UTUC who received the first of 6 once-weekly instillations of UGN-101 to the renal pelvis and calyces via retrograde ureteral catheter. Plasma samples were collected prior to instillation and 30 min, 1, 2, 3, 4, 5, and 6 h post-instillation. Safety was assessed by laboratory evaluations, physical exam, and adverse event monitoring., Results: The mean age of the six participants was 69 years; most were male (5/6) and Caucasian (5/6). Mean (SD) C max was 6.24 (4.11) ng/mL and mean T max was 1.79 (1.89) hours after instillation. Mean apparent t ½ following instillation was 1.27 (0.63) hours. Mean total systemic exposure to mitomycin up to 6 h post-instillation was 20.30 (19.69) ng h/mL. At 6 h post-instillation, mitomycin plasma concentrations of 5/6 participants were < 2 ng/mL. There were no clinically important adverse events or changes in laboratory values in any participant after a single instillation of UGN-101., Conclusion: The reverse thermal gel formulation of UGN-101 is associated with higher concentration and extended dwell time of mitomycin in contact with the urothelium of the upper urinary tract while limiting systemic absorption of mitomycin., Registration: NCT02793128; registered June 8, 2016.

Background: In prostate cancer treatment, lower urinary tract symptoms significantly improve with luteinizing hormone-releasing hormone antagonists use compared with agonists. However, it is unclear whether luteinizing hormone-releasing hormone antagonists can decrease acute urinary tract toxicity during external beam radiotherapy. This study aimed to assess whether luteinizing hormone-releasing hormone antagonists used as neoadjuvant therapy reduced acute urinary tract toxicity during external beam radiotherapy compared with luteinizing hormone-releasing hormone agonists., Methods: The study included 78 patients who underwent intensity-modulated radiation therapy for intermediate- and high-risk prostate cancer between April 2013 and January 2020. Irradiation was initiated after 3-6 months of neoadjuvant therapy. Androgen deprivation therapy was given to the intermediate-risk group for 6 months and the high-risk group for 2-3 years. The European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group toxicity grading scale was used to evaluate the urinary tract system toxicity. Relevant clinical factors were used in matching patients based on propensity scores to enable comparison between the groups., Results: Each group had 27 matched patients. There was no reduction in urinary tract toxicity with the use of luteinizing hormone-releasing hormon antagonists (P = 0.624). For patients with an International Prostate Symptom Score of ≥11 at the start of treatment, 18 patients in each group were matched. Significantly lower scores were observed in the luteinizing hormone-releasing hormon antagonist group (P = 0.041)., Conclusions: Luteinizing hormone-releasing hormon antagonists may reduce acute urinary tract toxicity during prostate cancer external beam radiotherapy compared with luteinizing hormone-releasing hormon agonists, in particular in patients with moderate to severe symptoms at the start of treatment., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Introduction: We investigated which benign prostatic hyperplasia-related lower urinary parameters are related to upper urinary tract obstruction and whether transurethral prostatectomy could improve upper urinary tract obstruction., Materials and Methods: Patients with prostate size over 30 g and urodynamically proven bladder outlet obstruction were enrolled in this prospective observational study. Bladder wall thickness and prostate size were measured by ultrasonography. A urodynamic study with laboratory tests including serum creatinine, prostate-specific antigen, and urinalysis was performed. Finally, a diuretic scintigraphy using mercaptoacetyltriglycine was performed. Tests except the urodynamic evaluation were repeated after transurethral prostatectomy., Results: In total, 24 patients were enrolled, and 19 patients completed the present study. The mean values of age (yrs), prostate size (mL), bladder thickness (mm), bladder compliance ( Δ mL/ Δ pr), and the bladder outlet obstruction index were 68.42 ± 8.25, 72.29 ± 32.78, 4.42 ± 1.14, 50.17 ± 32.15, and 82.11 ± 34.68, respectively. The mean T 1/2 (min) was 17.51 ± 16.34 on the left side and 15.30 ± 11.96 on the right side. Statistical analysis showed that bladder compliance and bladder thickness were preoperatively related to upper urinary tract obstruction ( p = 0.001 and p = 0.007, respectively). Diuretic mercaptoacetyltriglycine scan in 19 patients showed improvement 6 months after prostate surgery. Clinically significant proteinuria was associated with upper urinary tract obstruction, and proteinuria was also improved after prostate surgery., Conclusion: Storage-phase bladder dysfunction could be a reliable urodynamic factor for the indication of upper urinary tract obstruction in patients with benign prostatic hyperplasia, and upper urinary tract obstruction with subsequent kidney damage could be improved by surgical decompression of benign prostatic obstruction., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Sung Yong Cho et al.)

Renal interstitial fibrosis (RIF) is currently recognized as a crucial mechanism of the pathogenesis of chronic kidney disease (CKD). Kangxianling (KXL, anti-fibrin) is a traditional Chinese medicine that has been proven to significantly reduce the levels of ECM deposition and inhibit renal fibrosis. To characterize the mechanisms and drug targets of KXL, we established a RIF rat model and treated the rats with KXL and losartan. Histological analyses validated the establishment of the RIF model and the treatment effect of KXL. Multiple levels of transcriptomic datasets were generated using lncRNA, mRNA and microRNA sequencing of kidney tissues. Functional annotations and pathway analyses were performed to unravel the therapeutic mechanisms. A multi-level transcriptomic regulatory network was built to illustrate the core factors in fibrosis pathogenesis and therapeutic regulation. KXL and losartan significantly reduced the progression of RIF, and a better therapeutic effect was shown with higher concentrations of KXL. According to the cluster analysis results of the RNA-seq data, the normal control (NC) and high concentration of KXL (HK) treatment groups were the closest in terms of differentially expressed genes. The WNT, TGF-β and MAPK pathways were enriched and dominated the pathogenesis and therapy of RIF. miR-15b, miR-21, and miR-6216 were upregulated and miR-107 was downregulated in the fibrosis model. These small RNAs were shown to play critical roles in the regulation of the above fibrosis-related genes and could be inhibited by KXL treatment. Finally, based on the lncRNA datasets, we constructed a mRNA-lncRNA-miRNA coexpression ceRNA network, which identified key regulatory factors in the pathogenesis of kidney fibrosis and therapeutic mechanisms of KXL. Our work revealed the potential mechanism of the Chinese medicine Kangxianling in inhibiting renal interstitial fibrosis and supported the clinical use of KXL in the treatment of kidney fibrosis.

Several urinary disorders, including overactive bladder, urinary incontinence, and interstitial cystitis, are often characterized by negative urine cultures. The application of metagenomics (i.e., 16S rRNA microbial profiling or whole-genome shotgun sequencing) to urine samples has enabled the identification of previously undetected bacteria, contributing to the discovery and characterization of the urinary microbiome. The most frequent species isolated are Lactobacillus (15%), Corynebacterium (14.2%), Streptococcus (11.9%), Actinomyces (6.9%), and Staphylococcus (6.9%). Although several studies are emerging in this context, the role of urinary microbiota in the pathogenesis of infections and in tumor carcinogenesis remains unclear. Furthermore, data on the activity of gut microbiota in modulating sensitivity to immune checkpoint inhibitors in advanced cancer patients suggest that the influence of urinary microbiota on tumor response to anticancer therapy should also be investigated. Moreover, its possible relationship with tumor mutational burden, which is in turn correlated with response to immunotherapy, should be the focus of future studies. Of note, the effect of antibiotics on this complex scenario seems to deserve careful consideration.

The urinary tract toxicity is one of the major reasons for investigational drugs not coming into the market and even marketed drugs being restricted or withdrawn. The objective of this investigation is to develop an easily interpretable and practically applicable in silico prediction model of chemical-induced urinary tract toxicity by using naïve Bayes classifier. The genetic algorithm was used to select important molecular descriptors related to urinary tract toxicity, and the ECFP-6 fingerprint descriptors were applied to the urinary tract toxic/non-toxic fragments production. The established naïve Bayes classifier (NB-2) produced 87.3% overall accuracy of fivefold cross-validation for the training set and 84.2% for the external test set, which can be employed for the chemical-induced urinary tract toxicity assessment. Furthermore, six important molecular descriptors (e.g., number of N atoms, AlogP, molecular weight, number of H acceptors, number of H donors and molecular fractional polar surface area) and toxic and non-toxic fragments were obtained, which would help medicinal chemists interpret the mechanisms of urinary tract toxicity, and even provide theoretical guidance for hit and lead optimization.

Renal fibrosis is the common final outcome of nearly all progressive chronic kidney diseases (CKD) that eventually develop into end-stage renal failure, which threatens the lives of patients. Currently, there are no effective drugs for the treatment of renal fibrosis. However, studies have shown that certain plant natural products have a fibrosis-alleviating effect. Thus, we have screened a large number of natural products for their ability to protect against renal fibrosis and found that bisdemethoxycurcumin has a good therapeutic effect in renal fibrosis according to the data obtained in a mouse model of unilateral ureteral obstruction (UUO). The results indicate that bisdemethoxycurcumin can efficiently attenuate renal fibrosis induced by UUO. Additional studies of the bisdemethoxycurcumin mechanism of action in the treatment of renal fibrosis demonstrated that the therapeutic effect of bisdemethoxycurcumin is mediated by the specific induction of fibroblast apoptosis at a concentration of 20 μM. bisdemethoxycurcumin can efficiently protect against renal fibrosis both in vitro and in vivo. This discovery will provide new ideas for renal fibrosis treatment in clinics and a new direction for the development of effective drug therapy of renal fibrosis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The close anatomical relationship of the urogenital system is a significant, and sometimes limiting, factor in oncogynecology. Reducing adverse effects (treatment-associated toxicity) is an integral part of cancer treatment. Radical surgery, as well as oncological therapy, which represent milestones in the treatment of such malignancies, may require tailoring the extension of the intervention in order to preserve other non-gynecological structures. Despite the progress in minimally invasive surgery, and evolution of radiotherapy and systemic therapy, treatment-related complications remain; indeed, their increasing prevalence in women raises questions about quality of life., Aim: Here, we highlight the modalities used to treat gynecological cancer and discuss the most common urological adverse effects related to these interventions. Knowledge of side effects, as well as methods of prevention, is fundamental if we are to preserve quality of life., Conclusion: reatment of gynecological cancer is based on cooperation between members of the multidisciplinary team. From this point-of-view, combination of two radical modalities (mainly surgery and radiotherapy) remains problematic. However, the patients prognosis, and plans for other possible oncological therapies, play an essential role in management of urological adverse effects related to cancer treatment. Key words: gynecologic neoplasms - complication - urinary tract - quality of life This work was supported by project PROGES Q40. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 27. 9. 2018 Accepted: 21. 10. 2018.

Purpose: Coconut water has long been touted for its medicinal qualities including natural hydration. We sought to determine whether its consumption would induce changes to urinary lithogenic factors beyond changes in urine volume., Materials and Methods: After Institutional Review Board approval, volunteers with no prior history of nephrolithiasis were recruited. Each participant was randomized initially to either the coconut water or the water phase of the study. Participants kept meticulous food and fluid intake logs during the first phase of the study and were asked to replicate that diet for the second phase. For each phase the participant consumed 2L of either Taste of Nirvana® pure coconut water or tap water daily for four days. Participants were not restricted to consume additional fluid of their choice during their assigned study phase. During days 3 and 4 of each phase the participant collected a 24-hour urine specimen. Coconut water citrate and malate content were measured and were used along with the beverage pH to calculate the total alkali content of the coconut water. Supersaturation levels were calculated using Equil2. Nonparametric paired analysis using the Wilcoxon test was performed for statistical analysis., Results: There were 4 adult male and 4 adult female participants. Each individual's 24-hour urine collection had a creatinine excretion within 20% of the mean for each subject's four samples corroborating that all samples were collected properly. The two samples from each phase for each individual were averaged. The coconut water itself was also analyzed and it was calculated to have a total alkali content of 13.8 mEq/L. Consumption of coconut water significantly increased urinary citrate (29%, p=0.02), urinary potassium (130%, p=0.01), and urinary chloride (37%, p=0.03), without affecting urine pH (p=0.16) or volume beyond that of tap water (p=1.00)., Conclusions: Coconut water consumption increases urinary potassium, chloride, and citrate in nonstone forming individuals.

Urinary tract infections (UTIs) caused by Escherichia coli (E. coli) are the most common types of infections in women. The antibiotic resistance of E. coli is increasing rapidly, causing physicians to hesitate when selecting oral antibiotics. In this review, our objective is to ensure that clinicians understand the current seriousness of antibiotic-resistant E. coli , the mechanisms by which resistance is selected for, and methods that can be used to prevent antibiotic resistance.

Background/aim: Smoking is a risk factor for carcinogenesis and progression of urothelial cancer (UC). Green tea polyphenol inhibits these malignant behaviors and suppresses human antigen R (HuR) expression, which is associated with malignant aggressiveness. This study aimed to clarify the anti-cancer effects of green tea based on the smoking status of UC patients., Patients and Methods: Three hundred and sixty (260 with bladder cancer, BC and 100 with upper tract UC) patients were divided into three groups based on consumption of green tea: low (<1 cup/day, n=119), middle (1-4 cup/day, n=160), and high (>5 cup/day, n=81). HuR immunoreactivity was evaluated immunohistochemically in formalin-fixed specimens., Results: In never smokers, multivariate analysis showed that the frequency of green tea consumption was a significant predictor (middle: hazard ratio, HR, 0.36, p=0.002; high: HR, 0.20, p=0.003) of urinary tract recurrence. A high consumption of green tea was associated with low rates of urinary tract recurrence and up-grading in UC patients. In BC, high consumption was associated with a lower risk of up-grading (p=0.011) and up-staging (p=0.041) in recurrent cancer. HuR expression in the high-consumption group was lower (p=0.019) than that in other groups. These significant findings were not detected in ever smokers., Conclusion: High consumption of green tea suppressed urinary tract recurrence and the risks of up-grading and up-staging by recurrence in never smokers. Our results suggested that HuR expression played important roles in such mechanisms., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background and Purpose: The EMBRACE study is a prospective multi-institutional study on MRI guided adaptive brachytherapy (IGABT) in locally advanced cervix cancer (LACC). This analysis describes early to late urinary morbidity assessed by physicians and patients (PRO)., Material and Methods: A total of 1176 patients were analysed. Median follow up (FU) was 27 (1-83) months. Morbidity (CTCAE v.3) and PRO (EORTC QLQ-C30&CX24) was prospectively assessed at baseline (BL), and during FU., Results: The most frequent symptoms were frequency/urgency, incontinence, and cystitis with grade 2-4 prevalence rates of 4.3%, 5.0% and 1.7% and grade 1-4 prevalence rates of 24.5%, 16.1% and 5.8% at 3-years. The most frequent PRO endpoints were "urinary frequency" and "leaking of urine". Prevalence of "Quite a bit" or "very much" bother fluctuated from 14.0% to 21.5% for "frequency", while "leaking of urine" increased from 4.6% at BL to 9.3% at 3-years. Actuarial 3-year incidence of grade 3-4 urinary morbidity was 5.3% with most events being urinary frequency, incontinence and ureteral strictures. Grade 3-4 fistula, bleeding, spasm and cystitis were all <1.0% at 3/5-years. No grade 5 toxicity occurred., Conclusion: Urinary grade 3-4 morbidity with IGABT was limited. Urinary morbidity grade 2-4 comprises mainly frequency/urgency, incontinence and cystitis and has considerable prevalence in PRO. Various urinary morbidity endpoints have different patterns of manifestation and time course., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: To review the incidence of healthcare-associated infections/urinary tract infection (UTI), risk factors, microorganisms isolated and antibiotic resistances in patients who underwent lower urinary tract endoscopic surgery (LUTES) in a tertiary care hospital., Methods: A prospective observational study was carried out including 1,498 patients who undergo LUTES. Patients with and without UTI after surgery were compared. We analysed infection incidence, risk factors, microorganisms isolated and antibiotic resistances., Results: Postoperative UTI incidence was 4.7%. Risk factors found: higher American Society of Anesthesiologists classification (OR 2.82; 95% CI 1.8-4.5; p < 0.00), immunosuppression (OR 2.89; 95% CI 1.2-7.2; p = 0.01), indwelling urinary catheter prior admission (OR 2.6; 95% CI 1.6-4.2; p < 0.00) and postoperative catheterization longer than 2 days (OR 1.74; 95% CI 1.7-4.3; p < 0.00). Transurethral resection of the bladder (TURB) had the highest infection rates (5.5%). Microorganisms isolated were Pseudomonas aeruginosa (23.5%), Escherichia coli (17.6%), Klebsiella pneumoniae and Enterococcus spp (11.8%). Resistance rates for flourquinolones varied between 28 and 80%, and Carbapenem-resistant Enterobacteriaceae rose up 20%., Conclusions: Low percentage of UTI after endoscopic surgery was registered. TURB was the procedure with highest infection rate. Pseudomonas aeruginosa stands out as the most frequently isolated microorganism. Patient comorbidities, previous urinary catheter and postoperative catheter were identified as risk factors., (© 2018 S. Karger AG, Basel.)

Introduction: In recent years, prolonged ketamine abuse has been reported to cause urinary tract damage. However, there is little information on the pathological effects of ketamine from oral administration. We aimed to study the effects of oral ketamine on the urinary tract and the reversibility of these changes after cessation of ketamine intake., Methods: Rats were fed with illicit (a concoction of street ketamine) ketamine in doses of 100 (N=12), or 300 mg/kg (N=12) for four weeks. Half of the rats were sacrificed after the 4-week feeding for necropsy. The remaining rats were taken off ketamine for 8 weeks to allow for any potential recovery of pathological changes before being sacrificed for necropsy. Histopathological examination was performed on the kidney and urinary bladder., Results: Submucosal bladder inflammation was seen in 67% of the rats fed with 300 mg/kg illicit ketamine. No bladder inflammation was observed in the control and 100 mg/kg illicit ketamine groups. Renal changes, such as interstitial nephritis and papillary necrosis, were observed in rats given illicit ketamine. After ketamine cessation, no inflammation was observed in the bladder of all rats. However, renal inflammation remained in 60% of the rats given illicit ketamine. No dose-effect relationship was established between oral ketamine and changes in the kidneys., Conclusion: Oral ketamine caused pathological changes in the urinary tract, similar to that described in exposure to parenteral ketamine. The changes in the urinary bladder were reversible after short-term exposure.

Aim: This review article is a collaborative report based upon the Authors' presentations and Group discussion on the role of testosterone (T) in the male and female lower urinary tract (LUT) which took place at the 6th International Consultation on Incontinence Research Society's (ICI-RS) annual meeting, in Bristol, UK (September 8-10, 2015)., Methods: It comprises overviews and opinions on both the current state of knowledge of the role of T in LUT function and dysfunction in both sexes., Results: Results from animal studies suggest that T treatment may be beneficial for disorders of the LUT in women including urinary incontinence and pelvic organ prolapse. The need for clinical studies to evaluate the effect of T treatment in peri- and post-menopausal women, taking into account the type of applied androgen, the application form, timing and dosage, is especially emphasized. In males, findings on the impact of T on the male external urethral sphincter underscores that there is still much to learn about its role in male LUT physiology. The important topic of the use of T therapy in the treatment of enuresis in the young, both sexes, is also discussed. The importance of understanding the steroidogenic pathways linking T with estradiol is discussed as being of paramount importance in researching the unique actions of T in the LUT., Conclusion: The overall conclusion is that further research into the role of T in LUT function and dysfunction across genders and age groups (young to old) is extremely important. Neurourol. Urodynam. 36:859-862, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Estrogen supplementation is a key component of numerous mouse research models but can adversely affect the urinary system. The goal of this study was to develop a clinical scoring system and identify biomarkers of occult urinary tract lesions prior to the development of systemic illness in mice. Ovariectomized or sham-surgery SCID mice were implanted subcutaneously with a placebo pellet or one containing sustained-release estradiol (0.18 mg 60-d release 17β-estradiol). Mice were assessed twice weekly for 4 to 6 wk by using a clinical scoring system that included body condition, general activity, posture, hair coat, hydration, abdominal distension, urine staining of coat and skin, and ability to urinate. Samples were collected weekly for urinalysis, BUN, creatinine, and serum estradiol levels. Terminal samples were analyzed for histopathologic lesions. Compared with placebo controls, estradiolsupplemented mice had higher serum estradiol levels at weeks 2 and 3; significant differences in total clinical scores by the 3-wk time point; and in body condition, general activity, posture, hair coat, and urine staining scores by the 6-wk terminal time point. Urinary tract lesions included hydronephrosis, pyelonephritis, cystitis, and urolithiasis. All mice with urolithiasis had crystalluria, and 5 of the 6 mice with pyelonephritis or hydroureter had dilute urine (that is, specific gravity less than 1.030). However, these findings were not specific to mice with lesions. A total clinical score of 3.5 (maximum, 24) identified estradiol-supplemented mice with 83% specificity and 50% sensitivity, but no single clinical parameter, biomarker, or the total clinical score accurately predicted occult urinary tract lesions. Considering the lesions we observed, prudence is warranted when using pelleted sustained-release estradiol in mice, and important parameters to monitor for animal health include urine staining, body condition score, urine sediment, and urine specific gravity.

The clinical syndromes comprising urinary tract infection (UTI) continue to exert significant impact on millions of patients worldwide, most of whom are otherwise healthy women. Antibiotic therapy for acute cystitis does not prevent recurrences, which plague up to one fourth of women after an initial UTI. Rising antimicrobial resistance among uropathogenic bacteria further complicates therapeutic decisions, necessitating new approaches based on fundamental biological investigation. In this review, we highlight contemporary advances in the field of UTI pathogenesis and how these might inform both our clinical perspective and future scientific priorities., Competing Interests: D.A.H. serves on the Board of Directors of BioVersys AG, Basel, Switzerland., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Lower urinary tract (LUT) symptoms (LUTS), including frequency, urgency, incomplete voiding, and slow stream, are common in both men and women with advancing age. The most common cause for LUTS in aging men is benign prostatic hyperplasia. Some studies have also revealed an inverse association of serum testosterone levels with LUTS; however, the underlying mechanisms by which gonadal hormones affect the LUT have not been clarified. In the present study, we examined the effect of orchiectomy and testosterone replacement on LUT function in adult male Sprague-Dawley rats. Six weeks after bilateral orchiectomy or sham operations and 3 wk after injection of long-acting testosterone undecanoate (100 mg/kg im), transvesical cystometry and external urethral sphincter electromyogram (EUS EMG) recordings were performed under urethane anesthesia. The micturition reflex was elicited in both sham and orchiectomized animals. In orchiectomized rats, volume threshold for inducing micturition decreased by 47.6%; however, contraction amplitude, duration, and voiding efficiency were similar in sham and orchiectomized rats. The active period during EUS EMG bursting was lengthened during micturition in orchiectomized animals. Testosterone treatment, which normalized plasma testosterone levels, reversed these changes but also increased the duration of EUS EMG bursting. Orchiectomy also reduced mean voiding flow rate estimated from the duration of EUS EMG bursting, an effect that was not reversed by testosterone. The results indicate that orchiectomy affects both the active and passive properties of the bladder and urethra, and that many, but not all, of the changes can be reversed by testosterone., (Copyright © 2016 the American Physiological Society.)

Hydronephrosis is a commonly found disease state characterized by the dilation of renal calices and pelvis, resulting in the loss of kidney function in the severest cases. A generally accepted etiology of hydronephrosis involves the obstruction of urine flow along the urinary tract. In the recent years, we have developed a mouse model of hydronephrosis induced by lactational exposure to dioxin and demonstrated a lack of anatomical obstruction in this model. We also showed that prostaglandin E 2 synthesis system plays a critical role in the onset of hydronephrosis. In the present study, we found that neonatal hydronephrosis was not likely to be associated with functional obstruction (impaired peristalsis) but was found to be associated with polyuria and low urine osmolality with the downregulation of proteins involved in the urine concentrating process. The administration of an antidiuretic hormone analog to the dioxin-exposed pups not only suppressed the increased urine output but also decreased the incidence and severity of hydronephrosis. In contrast to the case in pups, administration of dioxin to adult mice failed to induce polyuria and upregulation of prostaglandin E 2 synthesis system, and the adult mice were resistant to develop hydronephrosis. These findings suggest the possibility that polyuria could induce hydronephrosis in the absence of anatomical or functional obstruction of the ureter. It is concluded that the present animal model provides a unique example of polyuria-associated type of hydronephrosis, suggesting a need to redefine this disease state., (Copyright © 2016 the American Physiological Society.)

Diagnosis of tuberculosis requires bacteriological confirmation. The sputum is the material most frequently used for this purpose. In the case of extra-pulmonary tuberculosis, it is necessary to obtain other materials, such as urine, pleural fluid, pericardial effusion, ascites, cerebrospinal fluid, sample of tissue, etc. However, compared with sputum, these materials are much less likely to successfully culture mycobacteria. We described a case of a young woman with suspected pulmonary tuberculosis, however confirmation of the disease was obtained from urine culture. Despite hemoptysis and radiological changes typical for tuberculosis, the cultures of mycobacteria from respiratory tract were negative. The patient did not report any symptoms from urinary tract, and urinalysis was normal, ultrasound however revealed changes in the left kidney which were typical for tuberculosis. The mycobacterial culture of urine was positive. Antimycobacterial drugs were applied with a good effect.

The herbicide itself and the degradation products are highly toxic on biological systems. The aim of this study is to investigate the potential toxic effects of trifluralin (TRF) on the urinary system of male rats and to investigate the protective effects of resveratrol (RSV) in TRF-induced urinary system damage. A total of 35 male Wistar rats were randomly divided into: (1) control group, (2) sham group, (3) low dose TRF group (0.8 g/kg/day), (4) high dose TRF group (2 g/kg/day) and (5) high dose TRF + RSV group 10 mg/kg/day. RSV was administered for 21 days by intragastric gavage at a dose of 10 mg/kg/day after induction of TRF. Kidney, ureter and urinary bladder tissue was examined using light microscopy and ultrastructurally. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling was performed to detect apoptosis. Superoxide dismutase (SOD), glutathion peroxidase (GPx) and malondialdehyde (MDA) levels were also evaluated biochemically for oxidative stress parameters. Histological evaluation showed that TRF increases apoptosis and oxidative stress, causes histological tissue damages and biochemical changes in the kidneys but does not cause any damage to the ureter and bladder. Treatment with RSV significantly attenuated tissue damage in the urinary system of rats. Apopitotic cells were significantly decreased in the treatment group. Additionally, treatment with RSV decreased SOD and GPx levels and increased MDA levels in the kidney tissue of animals subjected to TRF. These results show that RSV can significantly minimize histological damage and biochemical differences in treating TRF-induced kidney injury in rats., (© The Author(s) 2013.)

Ketamine is a short-acting anaesthetic agent that has gained popularity as a 'club drug' due to its hallucinogenic effects. Substance abuse should be considered in young adult patients who present with severe debilitating symptoms such as lower urinary tract symptoms, even though the use of controlled substances is rare in Singapore. Although the natural history of disease varies from person to person, a relationship between symptom severity and frequency/dosage of abuse has been established. It is important to be aware of this condition and have a high degree of clinical suspicion to enable early diagnosis and immediate initiation of multidisciplinary and holistic treatment. A delayed diagnosis can lead to irreversible pathological changes and increased morbidity among ketamine abusers.

The emergence of multidrug-resistant (MDR) uropathogens is making the treatment of urinary tract infections (UTIs) more challenging. We sought to evaluate the accuracy of empiric therapy for MDR UTIs and the utility of prior culture data in improving the accuracy of the therapy chosen. The electronic health records from three U.S. Department of Veterans Affairs facilities were retrospectively reviewed for the treatments used for MDR UTIs over 4 years. An MDR UTI was defined as an infection caused by a uropathogen resistant to three or more classes of drugs and identified by a clinician to require therapy. Previous data on culture results, antimicrobial use, and outcomes were captured from records from inpatient and outpatient settings. Among 126 patient episodes of MDR UTIs, the choices of empiric therapy against the index pathogen were accurate in 66 (52%) episodes. For the 95 patient episodes for which prior microbiologic data were available, when empiric therapy was concordant with the prior microbiologic data, the rate of accuracy of the treatment against the uropathogen improved from 32% to 76% (odds ratio, 6.9; 95% confidence interval, 2.7 to 17.1; P < 0.001). Genitourinary tract (GU)-directed agents (nitrofurantoin or sulfa agents) were equally as likely as broad-spectrum agents to be accurate (P = 0.3). Choosing an agent concordant with previous microbiologic data significantly increased the chance of accuracy of therapy for MDR UTIs, even if the previous uropathogen was a different species. Also, GU-directed or broad-spectrum therapy choices were equally likely to be accurate. The accuracy of empiric therapy could be improved by the use of these simple rules., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Impaired blood flow in lower urinary tract (LUT) tissues is a pathophysiological cause of LUT symptoms. We investigated the effects of the phosphodiesterase 5 (PDE5) inhibitor tadalafil on the sustained decrease in bladder blood flow (BBF) and time-dependent changes in BBF and prostate blood flow (PBF) resulting from ischemia/reperfusion in two rat models. In a rat model of bladder overdistension/emptying (O/E), the bladder was overdistended by saline infusion and emptied after 2h. Tadalafil was administered intraduodenally immediately after emptying. In a rat model of clamping/release (C/R), the abdominal aorta was clamped for 2h after a single oral dose of tadalafil and then the clamp was released. BBF in O/E and C/R rats and PBF in C/R rats were measured by laser Doppler flow imaging. BBF decreased on overdistension and partially recovered after emptying. A progressive decrease in BBF was observed after O/E, and this was prevented by tadalafil treatment. Both BBF and PBF decreased during clamping of the abdominal aorta and partially recovered after clamp removal. Oral pretreatment with tadalafil partially or completely prevented the decreases in BBF and PBF not only after clamp removal but also during clamping. PDE5 mRNA was highly expressed in the bladder and the supporting vasculature. Tadalafil inhibited the O/E-induced decrease in BBF and the C/R-induced time-dependent decreases in BBF and PBF. PDE5 inhibition by tadalafil may improve both BBF and PBF., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Context: Urothelial carcinoma in situ (CIS) has a high propensity for progression. It is usually reported within the heterogeneous context of non-muscle-invasive bladder cancer (NMIBC) but warrants special consideration., Objective: To review the contemporary literature on the diagnosis and management of CIS., Evidence Acquisition: A systematic search using broad terms to capture the diagnosis and treatment of CIS was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analysis criteria. Full-text original articles, reviews, and editorials from 1966 to 2014 in English were included. References from selected articles, relevant guidelines, and conference abstracts were searched. Abstracts were excluded., Evidence Synthesis: A total of 1887 articles were identified, of which 120 were used in this review. Most reports were retrospective and heterogeneous in caseload. There is a lack of standardised classification of CIS. Many studies consider CIS in the context of NMIBC without a clear separation of the subset with CIS. Recent prospective phase 2 and 3 studies have improved the evidence base., Conclusions: We are beginning to understand that CIS has a spectrum of biologic potential. Bacillus Calmette-Guérin immunotherapy appears superior to other intravesical agents and may alter the natural history of CIS. New imaging modalities, agents, and treatment strategies have emerged in recent years with the aim of better identification of CIS, more bladder-preserving treatments, and prevention of surgical overtreatment., Patient Summary: Improvements in imaging techniques combined with new bladder-preserving treatments will continue to have an impact on the outcomes of bladder carcinoma in situ., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: To assess the efficacy and safety of LY500307, a selective estrogen receptor beta agonist, on lower urinary tract symptoms (LUTS) in patients with enlarged prostate secondary to BPH., Methods: In a randomized, double-blind, placebo-controlled, parallel phase 2, efficacy and safety study, eligible patients with moderate to severe LUTS and prostatic enlargement (⩾30 ml) were randomized to placebo or LY500307 at 1, 3, 10 and 25 mg once daily for 24 weeks. Primary efficacy end point was change in total International Prostate Symptoms Score (IPSS) after 24 weeks. Secondary end points included changes in total prostate volume (TPV) that served as a proof of concept end point, as well as IPSS quality of life, maximum peak urine flow rate (Qmax) and PSA and safety (adverse events, laboratory test)., Results: A total of 414 patients were randomized when the study was terminated because of insufficient TPV reduction, based on a priori defined interim analysis. The IPSS mean change from baseline to end point was -3.4±6.8 in the placebo group and -1.3±6.6, -2.6±7.0, -3.7±6.7 and -4.4±5.7 in the 1, 3, 10 and 25 mg LY500307-treated groups, respectively (P>0.05). Similarly, no treatment effect was observed for any of the secondary efficacy measures. Incidence of adverse events was comparable between treatment groups, and no clinically meaningful changes in laboratory tests were observed., Conclusions: LY500307 was well tolerated in BPH patients with LUTS at doses up to 25 mg once daily for 24 weeks. The study was terminated early because of inadequate efficacy.

Sepsis is one of the oldest and most elusive syndromes in medicine. With the confirmation of germ theory by Semmelweis, Pasteur, and others, sepsis was considered as a systemic infection by a pathogenic organism. Although the germ is probably the beginning of the syndrome and one of the major enemies to be identified and fought, sepsis is something wider and more elusive. In this chapter clinically relevant themes of sepsis will be approached to provide an insight of everyday clinical practice for healthcare workers often not directly involved in the patient's management.

This review highlights the recent clinical research that supports the therapeutic utility of ketamine as a multifaceted drug. After long-term use as a dissociative anesthetic, it has re-emerged as a useful agent for ameliorating pain, asthmaticus, and depression. In addition, it is also a substance of abuse. Chronic ketamine abuse over prolonged periods (weeks, months, and years) can produce toxicity to the gastrointestinal and urinary tract. In this review, we described the recent progress on its clinical uses and abuses., (© 2014 John Wiley & Sons Ltd.)

Purpose: (18)F-Fluoroethylcholine ((18)F-FECh) is excreted via the urinary system with high activity accumulation in the urinary bladder. Furosemide and oral hydration can be administered concomitantly to reduce urinary activity to provide better detectability of retroperitoneal and pelvic lesions. Currently it is unknown if there is any effect of furosemide on (18)F-FECh uptake in organs, tissues and tumour lesions and the extent to which image quality along the urinary tract may be improved by furosemide., Methods: We retrospectively analysed 217 (18)F-FECh PET/CT examinations from 213 patients with known prostate cancer (PCa), performed either with oral hydration (109) or furosemide 20 mg together with oral hydration (108). Maximum (18)F-FECh uptake in different organs, tissues, lymph nodes and osseous metastases was quantified in terms of standardized uptake value (SUV) in a volume of interest and compared between the two groups. To characterize the impact of furosemide on lesion detectability a three-point rating scale was used to assess the presence of focal activity spots in the ureters and of perivesicular artefacts., Results: Patient characteristics and distribution of tumour lesions were well balanced between the two groups. Overall, SUVmax values from normal organs were increased after furosemide compared to the values in patients scanned without furosemide. Significant changes were observed in the salivary glands, liver, spleen, pancreas, kidneys, gluteus muscle and perirenal fat. SUVmax values were significantly decreased after furosemide in lymph node metastases (SUVmax 4.81 ± 2.68 vs. 6.48 ± 4.22, p = 0.0006), but not in osseous metastases. Evaluation of image quality along the urinary tract revealed significantly better depiction of the perivesicular space and significantly less focal tracer accumulation in the ureters in patients receiving furosemide, but the number of detected lymph nodes was not significantly different., Conclusion: Furosemide administration reduced choline uptake in tumour lesions, especially significant in pelvic lymph node metastases. Although furosemide administration improved image quality, optimal image quality may also be obtained by adequate hydration without the risk of diminishing choline uptake in PCa lesions. Therefore a controlled hydration protocol seems more appropriate than administration of furosemide.

Urea transport (UT) proteins of the UT-A class are expressed in epithelial cells in kidney tubules, where they are required for the formation of a concentrated urine by countercurrent multiplication. Here, using a recently developed high-throughput assay to identify UT-A inhibitors, a screen of 50,000 synthetic small molecules identified UT-A inhibitors of aryl-thiazole, γ-sultambenzosulfonamide, aminocarbonitrile butene, and 4-isoxazolamide chemical classes. Structure-activity analysis identified compounds that inhibited UT-A selectively by a noncompetitive mechanism with IC50 down to ∼1 μM. Molecular modeling identified putative inhibitor binding sites on rat UT-A. To test compound efficacy in rats, formulations and administration procedures were established to give therapeutic inhibitor concentrations in blood and urine. We found that intravenous administration of an indole thiazole or a γ-sultambenzosulfonamide at 20 mg/kg increased urine output by 3-5-fold and reduced urine osmolality by ∼2-fold compared to vehicle control rats, even under conditions of maximum antidiuresis produced by 1-deamino-8-D-arginine vasopressin (DDAVP). The diuresis was reversible and showed urea > salt excretion. The results provide proof of concept for the diuretic action of UT-A-selective inhibitors. UT-A inhibitors are first in their class salt-sparing diuretics with potential clinical indications in volume-overload edemas and high-vasopressin-associated hyponatremias., (© FASEB.)

We present an overview of the current pharmacological treatment of urinary incontinence (UI) in women, according to the latest evidence available. After a brief description of the lower urinary tract receptors and mediators (detrusor, bladder neck, and urethra), the potential sites of pharmacological manipulation in the treatment of UI are discussed. Each class of drug used to treat UI has been evaluated, taking into account published rate of effectiveness, different doses, and way of administration. The prevalence of the most common adverse effects and overall compliance had also been pointed out, with cost evaluation after 1 month of treatment for each class of drug. Moreover, we describe those newer agents whose efficacy and safety need to be further investigated. We stress the importance of a better understanding of the causes and pathophysiology of UI to ensure newer and safer treatments for such a debilitating condition.

In this study, we propose a novel statistical framework for detecting progressive changes in molecular traits as response to a pathogenic stimulus. In particular, we propose to employ Bayesian hierarchical models to analyse changes in mean level, variance and correlation of metabolic traits in relation to covariates. To illustrate our approach we investigate changes in urinary metabolic traits in response to cadmium exposure, a toxic environmental pollutant. With the application of the proposed approach, previously unreported variations in the metabolism of urinary metabolites in relation to urinary cadmium were identified. Our analysis highlights the potential effect of urinary cadmium on the variance and correlation of a number of metabolites involved in the metabolism of choline as well as changes in urinary alanine. The results illustrate the potential of the proposed approach to investigate the gradual effect of pathogenic stimulus in molecular traits.

Background: Nephrogenic diabetes insipidus (NDI) is characterized by the kidney's inability to concentrate urine, which causes intense polyuria that may lead to urinary tract dilation. We report the morphological findings of the urinary tract in ten boys with NDI specifically addressing the presence and changes of urinary tract dilation during treatment., Diagnosis/treatment: Patients were diagnosed at a median age of 1.6 years (range, 0.16-6.33 years) and treated with a low osmotic diet, hydrochlorothiazide-amiloride and indomethacin, which decreased the diuresis from a median of 10.5 ml/kg/h to 4.4 ml/kg/h (p < 0.001). Three patients showed normal renal ultrasound before treatment until last control, while the remaining seven showed urinary tract dilation. In this second group, dilation was reduced with treatment in four patients and disappeared in the remaining three. Children without dilation or in whom the dilation disappeared were diagnosed and treated earlier than those with persistent dilation (median 1.66 versus 4.45 years, respectively). After a median of 10.4 (range, 2.3-20.3) years of follow-up, no patients showed urological complications., Conclusions: Medical treatment of the disease improved the dilation in all cases, preventing its potential complications. Regardless of the good outcome of our patients, periodic urologic follow-up is recommended in NDI patients.

Renal pacemakers set the origin and frequency of the smooth muscle contractions that propel wastes from the kidney to the bladder. Although congenital defects impairing this peristalsis are a leading cause of pediatric renal failure, the mechanisms underlying renal pacemaker activity remain unknown. Using ratiometric optical mapping and video microscopy, we discovered that hyperpolarization-activated cation (HCN) channel block with the specific anatagonist ZD7288 (30 μm; IC50) abolished the pacemaker depolarizations that initiate murine upper urinary tract peristalsis. Optical mapping and immunohistochemistry indicate that pacemaker potentials are generated by cells expressing HCN isoform-3, and that HCN3(+) cells are coupled to definitive smooth muscle via gap junctions. Furthermore, we demonstrate that HCN3(+) cells coexpress T-type Ca(2+) (TTC) channels and that TTC channel inhibition with R(-)efonidipine or NNC55-0396 decreased contractile frequency in a dose-dependent manner. Collectively, these data demonstrate that HCN3(+)/TTC(+) cells are the pacemakers that set the origin and rate of upper urinary tract peristalsis. These results reveal a conserved mechanism controlling autorhythmicity in 2 distinct muscle types, as HCN and TTC channels also mediate cardiac pacemaker activity. Moreover, these findings have translational applications, including the development of novel diagnostics to detect fetal urinary tract motility defects prior to renal damage.-Hurtado, R., Bub, G., Herzlinger, D. A molecular signature of tissues with pacemaker activity in the heart and upper urinary tract involves coexpressed hyperpolarization-activated cation and T-type Ca(2+) channels.

Unlabelled: Urease is a virulence factor for the Gram-positive urinary tract pathogen Staphylococcus saprophyticus. The susceptibility of this enzyme to chemical inhibition was determined using soluble extracts of Staph. saprophyticus strain ATCC 15305. Acetohydroxamic acid (Ki = 8.2 μg ml(-1) = 0.106 mmol l(-1) ) and DL-phenylalanine hydroxamic acid (Ki = 21 μg ml(-1) = 0.116 mmol l(-1) ) inhibited urease activity competitively. The phosphorodiamidate fluorofamide also caused competitive inhibition (Ki = 0.12 μg ml(-1) = 0.553 μmol l(-1) = 0.000553 mmol l(-1) ), but the imidazole omeprazole had no effect. Two flavonoids found in green tea extract [(+)-catechin hydrate (Ki = 357 μg ml(-1) = 1.23 mmol l(-1) ) and (-)-epigallocatechin gallate (Ki = 210 μg ml(-1) = 0.460 mmol l(-1) )] gave mixed inhibition. Acetohydroxamic acid, DL-phenylalanine hydroxamic acid, fluorofamide, (+)-catechin hydrate and (-)-epigallocatechin gallate also inhibited urease activity in whole cells of strains ATCC 15305, ATCC 35552 and ATCC 49907 grown in a rich medium or an artificial urine medium. Addition of acetohydroxamic acid or fluorofamide to cultures of Staph. saprophyticus in an artificial urine medium delayed the increase in pH that normally occurs during growth. These results suggest that urease inhibitors may be useful for treating urinary tract infections caused by Staph. saprophyticus., Significance and Impact of the Study: The enzyme urease is a virulence factor for the Gram-positive urinary tract pathogen Staphylococcus saprophyticus. We have shown that urease activity in cell-free extracts and whole bacterial cells is susceptible to inhibition by hydroxamates, phosphorodiamidates and flavonoids, but not by imidazoles. Acetohydroxamic acid and fluorofamide in particular can temporarily delay the increase in pH that occurs when Staph. saprophyticus is grown in an artificial urine medium. These results suggest that urease inhibitors may be useful as chemotherapeutic agents for the treatment of urinary tract infections caused by this micro-organism., (© 2013 The Society for Applied Microbiology.)

Objective: We aimed to evaluate whether changes in urinary and sexual function can influence health-related quality of life., Patients and Methods: Out of 54 recruited patients, 36 were enrolled, and data for 30 participants with erectile dysfunction were available. At baseline and after 1 and 2 months, each participant completed the International Index of Erectile Function (IIEF-15), the International Prostate Symptom Score (IPSS) and the Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36). Uroflowmetry, post-voiding residual volume and the nocturnal penile tumescence (NPT) test were performed at baseline and at the study's conclusion., Results: Compared with baseline, the IPSS, IIEF-15, peak urinary flow rate, NPT parameters and mental component of the SF-36 exhibited significant improvement at the study's conclusion. Among the symptomatic parameters, the changes in the storage and erectile function parameters contributed significantly to the change in the mental component score on the SF-36 (p = 0.007, R(2) = 0.502)., Conclusions: The daily administration of low-dose mirodenafil (50 mg) produced improvements in urinary and erectile function with or without sexual stimulation. Furthermore, this therapy enhanced the mental component of health-related quality of life by improving storage and erectile symptoms., (© 2014 S. Karger AG, Basel.)

We conducted a retrospective analysis of acute bacterial prostatitis (ABP) secondary to manipulation to document clinical features, management and microbiology based on the route of prior manipulation, which can be divided into two subgroups: transrectal and transurethral procedure. The medical records of 158 cases compatible with a confirmed diagnosis of ABP secondary to manipulation from 7 urological centers between 2001 and 2012 were reviewed. When subcategorized according to route of prior manipulation of the lower urinary tract, there were distinct differences between transrectal and transurethral manipulation group with regard to clinical and microbiological features. Escherichia coli was the most common causative bacterium in both groups, but Pseudomonas spp. were much more dominant pathogens in the group by transurethral manipulation than transrectal manipulation group. The susceptibilities to second-, third- and fourth-generation cephalosporins, amikacin, carbapenem and aztreonam were shown to be very low in the transurethral manipulation group. Therefore, it will take account the difference in antibiotic selection in the patients with ABP secondary to manipulation according to the manipulation route., (Copyright © 2013. Published by Elsevier Ltd.)

The female genital and lower urinary tracts share a common embryological origin, arising from the urogenital sinus and both are sensitive to the effects of the female sex steroid hormones throughout life. Estrogen is known to have an important role in the function of the lower urinary tract and estrogen and progesterone receptors have been demonstrated in the vagina, urethra, bladder and pelvic floor musculature. In addition estrogen deficiency occurring following the menopause is known to cause atrophic change and may be associated with lower urinary tract symptoms such as frequency, urgency, nocturia, urgency incontinence and recurrent infection. These may also co-exist with symptoms of urogenital atrophy such as dyspareunia, itching, vaginal burning and dryness. Epidemiological studies have implicated estrogen deficiency in the aetiology of lower urinary tract symptoms with 70% of women relating the onset of urinary incontinence to their final menstrual period. Whilst for many years systemic and vaginal estrogen therapy was felt to be beneficial in the treatment of lower urinary and genital tract symptoms this evidence has recently been challenged by large epidemiological studies investigating the use of systemic hormone replacement therapy as primary and secondary prevention of cardiovascular disease and osteoporosis. The aim of this paper is to examine the effect of the sex hormones, estrogen and progesterone, on the lower urinary tract and to review the current evidence regarding the role of systemic and vaginal estrogens in the management of lower urinary tract symptoms and urogenital atrophy.

Based on a consistent bulk of experimental and epidemiologic works, we proposed that abnormal metabolism and/or dietary deprivation of essential polyunsaturated fatty acids by inducing a chronic and subclinical essential fatty acid deficiency (EFAD) in urothelial cell membranes may enhance the risk for urinary tract tumor (UTT) development. This threat may be enhanced by the unusual fact that the fatty-acid profile of the normal urothelium is similar to that reported in EFAD. The risk for UTT may be worsened when coexisting with a low-grade chronic inflammation (LGCI) state induced by urolithiasis or disbalance management of peroxides, free radical molecules, and their quenchers. There is cumulative evidence linking the LGCI of the urinary tract mucosa, calculi, and UTT, due to the long-standing release of promitotic, promutagen, and pro-inflammatory antiapoptotic cytokines in these conditions. The dual role played by pro- and anti-inflammatory eicosanoids and bioactive lipids, cytokines, and the disbalance of lipid peroxidation is discussed, concluding that the moderate, long-standing consumption or dietary supplementation of ω-3 PUFAs may improve the chances of avoiding UTT development., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To investigated the effect and mechanism of Fangjihuangqi Tang (FHT) on lower urinary tract dysfunction induced by benign prostatic hyperplasia (BPH) in rats., Methods: Male rats were randomly divided into seven groups: normal, model, finasteride (0.5 mg/ kg), terazosin (0.5 mg/kg), and FHT (10, 5, 2.5 g/kg). Rats were administered testosterone (0.5 mg sc) for 6 weeks after orchiectomy, excluding the normal group. All rats were intragastrically administered assigned drugs for 4 weeks from the third week. Urodynamics were assessed in rats under anesthesia. Serum dihydrotestosterone (DHT) and prostatic acid phosphatase (PAP) were measured. The prostate index (PI), bladder index (BI), and pathological detection were evaluated., Results: In the model group, the PI, BI, serum DHT, serum PAP, threshold pressure (TP), micturition pressure (MP), and residual urine volume (RV) were significantly higher. Moreover, inter-micturition duration (IMD) was significantly lower and the prostatic and bladder showed obvious pathological changes. The IMD was significantly higher, while BI, TP, MP, and RV were significantly lower and bladder pathological changes were alleviated in the FHT (10, 5 g/kg), finasteride, and terazosin groups. The PI, DHT, and PAP were significantly lower in the finasteride group, but they did not change significantly in the FHT (10, 5, 2.5 g/kg) and terazosin groups., Conclusion: FHT could relieve symptoms of lower urinary tract dysfunction in BPH rats but with no apparent effect on reducing the volume of the enlarged prostate itself.

This review summarizes the most recent scientific literature and regulations regarding analytical chemistry, toxicology, epidemiology, exposure, and risk assessment of melamine in infant formula. For analyses, enzyme-linked immunosorbent assay, high-performance liquid chromatography, capillary electrophoresis, gas chromatography coupled with mass spectrometry and liquid chromatography coupled with tandem mass spectrometry have commonly been used. Organization of proficiency test programs provided good evidence to facilitate granting laboratories accreditation and to ascertain the measurement reliability of melamine methods. Metabolic studies demonstrated that melamine is predominantly restricted to blood or extracellular fluid and is not extensively distributed to organs and tissues. Studies of human renal histopathology and clinical diagnoses indicated that melamine-related obstructive nephropathy derives from melamine precipitation in the lower urinary tract, with stones that are thought to be melamine-uric acid complexes. Epidemiologic studies showed that the occurrence of melamine-related urolithiasis is related to both the concentration of melamine in ingested milk products and the duration of ingestion. Long-term follow-up cohort studies should be continued to further investigate the epidemic and chronic hazard of melamine-induced nephrotoxicity. The World Health Organization set a tolerable daily intake of 0.2 mg/kg bw/day to be applied to "the whole population including infants". Other authorities and research institutes have set/proposed lower values., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

To date, benign diseases of the male and female lower urinary and genital tract, such as erectile dysfunction, bladder overactivity, lower urinary tract symptomatology secondary to benign prostatic hyperplasia and symptoms of female sexual dysfunction (including arousal and orgasmic disorders), can be therapeutically approached by influencing the function of the smooth musculature of the respective tissues. The use of isoenzyme-selective phosphodiesterase (PDE) inhibitors is considered a great opportunity to treat various diseases of the human urogenital tract. PDE inhibitors, in particular the PDE5 (cyclic GMP PDE) inhibitors avanafil, lodenafil, sildenafil, tadalafil, udenafil and vardenafil, are regarded as efficacious, having a fast onset of drug action and an improved effect-to-adverse event ratio, combining a high response rate with the advantage of an on-demand intake. The purpose of this review is to summarize recent as well as potential future indications, namely, erectile dysfunction, Peyronie's disease, overactive bladder, urinary stone disease, lower urinary tract symptomatology secondary to benign prostatic hyperplasia and premature ejaculation, for the use of PDE inhibitors in clinical urology.

Objectives: To investigate the effect of phosphodiesterase type 5 inhibitor on urinary continence recovery after bilateral nerve-sparing radical prostatectomy., Methods: We analyzed data of 393 open bilateral nerve-sparing radical prostatectomies carried out between 2005 and 2010. Patients who recovered urinary continence within the first month after catheter removal (n = 52) were excluded. This resulted in 341 evaluable patients. Urinary continence recovery was defined as being completely pad free over a period of 24 h. Patients were stratified according to postoperative daily (n = 58; 17%), on-demand (n = 112; 32.8%) and no (n = 171; 50.1%) phosphodiesterase type 5 inhibitor use. The effect of phosphodiesterase type 5 inhibitor use on urinary continence was assessed using the Kaplan-Meier method. Uni- and multivariable Cox regression analyses were used to test the association between phosphodiesterase type 5 inhibitor and urinary continence recovery after adjusting for cofounders., Results: At a mean follow up of 36.4 months after surgery (median: 33), 288 patients (84.5%) recovered urinary continence after bilateral nerve-sparing radical prostatectomy. Patients who did not use phosphodiesterase type 5 inhibitor after surgery had lower rates of urinary continence recovery at 1- and 2-year follow up as compared with patients taking phosphodiesterase type 5 inhibitor (67.1 vs 86.7% and 76 vs 94.4%, respectively; P < 0.001). After adjusting for all confounders, multivariable analysis showed that phosphodiesterase type 5 inhibitor use, either on demand or daily, had a positive impact on urinary continence recovery (P = 0.03)., Conclusions: Patients taking phosphodiesterase type 5 inhibitor have higher urinary continence recovery rates as compared with patients left untreated after bilateral nerve-sparing radical prostatectomy. An improvement in sphincteric and pelvic floor blood supply might be responsible for this beneficial effect associated with the use of phosphodiesterase type 5 inhibitor., (© 2012 The Japanese Urological Association.)