Prediction of clinically significant prostate cancer through urine metabolomic signatures: A large-scale validated study.

PURPOSE: Currently, there are no accurate markers for predicting potentially lethal prostate cancer (PC) before biopsy. This study aimed to develop urine tests to predict clinically significant PC (sPC) in men at risk. METHODS: Urine samples from 928 men, namely, 660 PC patients and 268 benign subjects, were analyzed by gas chromatography/quadrupole time-of-flight mass spectrophotometry (GC/Q-TOF MS) metabolomic profiling to construct four predictive models. Model I discriminated between PC and benign cases. Models II, III, and GS, respectively, predicted sPC in those classified as having favorable intermediate risk or higher, unfavorable intermediate risk or higher (according to the National Comprehensive Cancer Network risk groupings), and a Gleason sum (GS) of ≥ 7. Multivariable logistic regression was used to evaluate the area under the receiver operating characteristic curves (AUC). RESULTS: In Models I, II, III, and GS, the best AUCs (0.94, 0.85, 0.82, and 0.80, respectively; training cohort, N = 603) involved 26, 24, 26, and 22 metabolites, respectively. The addition of five clinical risk factors (serum prostate-specific antigen, patient age, previous negative biopsy, digital rectal examination, and family history) significantly improved the AUCs of the models (0.95, 0.92, 0.92, and 0.87, respectively). At 90% sensitivity, 48%, 47%, 50%, and 36% of unnecessary biopsies could be avoided. These models were successfully validated against an independent validation cohort (N = 325). Decision curve analysis showed a significant clinical net benefit with each combined model at low threshold probabilities. Models II and III were more robust and clinically relevant than Model GS. CONCLUSION: This urine test, which combines urine metabolic markers and clinical factors, may be used to predict sPC and thereby inform the necessity of biopsy in men with an elevated PC risk.

Sleep quality mediates the relationship between lower urinary tract symptoms and health-related quality of life in women with type-II diabetes.

AIM: To examine the mediating effect of sleep quality on the relationship between lower urinary tract symptoms and health-related quality of life in women with type-II diabetes. DESIGN: A cross-sectional study. METHODS: A study questionnaire comprising three valid instruments was used to obtain data about lower urinary tract symptoms, sleep quality and physical and mental component summary health-related quality of life between July 2017 and December 2018 (n = 343). Pearson's correlation coefficients were estimated initially to examine the relationships between the three variables. Multiple regression models were tested using a regression-based approach Hayes PROCESS macro for SPSS to examine the significance of proposed mediation effects. RESULTS: Most participants experienced at least one urinary symptom (n = 268, 78.1%). The total number of types of lower urinary tract symptoms experienced by participants was significantly inversely correlated with physical and mental component summary health-related quality of life, and sleep quality. Participants' sleep quality was significantly correlated with physical and mental component summary health-related quality of life. The relationships of lower urinary tract symptoms with physical and mental component summary health-related quality of life were, respectively, fully and partially mediated by sleep quality. CONCLUSION: Sleep quality played a mediating role on the relationship between lower urinary tract symptoms and health-related quality of life. Our findings could lead to improvements of diabetes care in nursing and healthcare practices. IMPACT: Understanding the role of sleep quality in the adverse effects of lower urinary tract symptoms on health-related quality of life contributes to the development and delivery of appropriate strategies to promote optimal health-related quality of life. We recommended including assessments of lower urinary tract symptoms, sleep and health-related quality of life in routine diabetes management. Nurses and healthcare professionals should concurrently reduce lower urinary tract symptoms and improve sleep to achieve this population's optimal health-related quality of life. PATIENTS OR PUBLIC CONTRIBUTION: We recruited a sample of older women with type-II diabetes at the endocrinology and metabolism outpatient departments of two hospitals. Study participants provided responses on the study questionnaires. The two hospitals provided needed supports (e.g., height/weight scales, suitable places for interview) during the data collection process.

Dual effect of chitosan activated platelet rich plasma (cPRP) improved erectile function after cavernous nerve injury.

BACKGROUND: The intracavernosal (IC) injection of chitosan activated platelet rich plasma (cPRP) has shown to improve the erectile dysfunction in cavernous nerve injury rat model. However, the action target of PRP in improving neurogenic erectile dysfunction remains unclear. We aimed to determine the effect of cPRP action at early stage that further mediates its effect on erectile function (EF) recovery in the bilateral cavernous nerve crushing (BCNC) injury rat model. METHODS: Fifty-four rats were randomly divided into two equal groups: intracavernosal ( IC) injection of saline after BCNC (group 1) and IC injection of cPRP after BCNC (group 2). Five animals in each group were euthanized at 3, 7 and 14 day (d) post-injection, and the tissues were harvested to conduct transmission electron microscopy and histological assays. Six animals in each group were used to determine the recovery of EF at 14 and 28 d post-injury. RESULTS: IC injections of cPRP increased all EF parameters at 28 d and 14 d post-injury (p < 0.05). cPRP injections simultaneously prevented the loss of neuronal nitric oxide synthase-positive neurons (p < 0.05) and nerve fibers (p < 0.05) in the major pelvic ganglion and cavernous nerve (CN), respectively, compared with saline injections. This simultaneous accelerated the regeneration of myelinated axons of the CN, reduced apoptosis, and enhanced the proliferation of the corporal smooth muscle cells at an earlier stage. CONCLUSION: These results suggest that the application of cPRP was beneficial to restore EF via neuroprotective and tissue-protective effects at early stage.

Therapeutic efficacy and cognitive adverse events of overactive bladder medication in patients with central nervous system Disorders-A cohort study.

PURPOSE: This cohort study evaluates therapeutic efficacy and adverse events (AEs) of various overactive bladder (OAB) medications for patients with central nervous system (CNS) disorders. METHODS: Patients with OAB and CNS disorders were prospectively enrolled. They were randomly allocated to 3 different treatment subgroups: (1) mirabegron 50 mg once daily (2) solifenacin 5 mg per day, and (3) combined solifenacin 5 mg and mirabegron 50 mg once daily. Efficacy and safety questionnaires and objective parameters were compared among the subgroups, and subgroups between baseline and 3 and 6 months after treatment. AEs, including cognitive dysfunction, were assessed using the Mini-Mental State Examination (MMSE). RESULTS: 102 patients (mean age, 71.8 ± 8.7 years) were enrolled, including 35, 36, and 31 patients received mirabegron monotherapy, solifenacin monotherapy, and combination therapy, respectively. OAB symptoms scores all significantly improved 3 months after treatment in different subgroup. However, PVR increased and VE decreased significantly after treatment in patients receiving solifenacin monotherapy and combination therapy. Dry mouth and constipation were the most common AEs, especially in the solifenacin and combination subgroups. Mild incidence of AEs was noted in patients receiving mirabegron monotherapy. No significant change in MMSE was noted among the subgroups after treatment. CONCLUSION: OAB medication had good therapeutic efficacy in patients who had OAB with CNS disorders, especially in cerebrovascular accident and parkinsonism. No OAB medication or their combination affected cognitive function, whereas minimal AEs were noted with mirabegron. Mirabegron could be recommended as the first choice for managing OAB in these patients.

Intracavernous Injection of Platelet-Rich Plasma Therapy Enhances Erectile Function and Decreases the Mortality Rate in Streptozotocin-Induced Diabetic Rats.

Erectile dysfunction (ED) is an agonizing complication of diabetes mellitus (DM) and it is challenging to treat ED in DM patients. Platelet-rich plasma (PRP) is a unique therapeutic strategy comprising intrinsic growth factors. An attempt was made to explore the potentiality of the PRP treatment in DM-induced ED rats in various groups (control, DM-non-ED, DM-ED, and DM-ED treated with PRP). Streptozotocin (STZ) was used to induce DM in rats. The blood glucose levels of the DM rats were maintained at >300 mg/dl. In the 18-week experiment, survival rate, body weight, intracavernous pressure (ICP) variations, and arterial blood pressure were analyzed. The tissue restoration results were validated by histological, immunofluorescence, and transmission electron microscopic analysis. PRP treatment of DM-ED rats significantly increased all parameters of erectile function compared to pre-treatment of PRP and DM-ED treated with vehicle. The histological results revealed that PRP treatment substantially enhanced the regeneration of myelinated nerves and decreased the atrophy of corporal smooth muscle. Notably, the PRP treatment immensely enhanced the survival rate in post-surgery DM-ED rats. These results indicated certain benefits of PRP treatment in delaying damage and preventing post-surgery complications in DM patients. Hence, PRP treatment is a novel multifactorial strategy for DM-ED patients.

Development of the Interstitial Cystitis Self-Help and Medical Resources Scale (ICSR) for Women with Interstitial Cystitis.

Background and Objectives: Women with interstitial cystitis (IC) suffer from spontaneous serious bladder pain symptoms without immediate resolution. Women with IC may lack knowledge of how to help themselves. Therefore, a measurement of IC self-help and medical-resource-seeking for women with IC is needed. Materials and Methods: This study recruited 100 women with IC from a teaching hospital in Northern Taiwan. The reliability and validity of the Interstitial Cystitis Self-Help and Medical Resources Scale (ICSR) were assessed using expert validity, confirmatory factor analysis (CFA) to test the construct validity, composite reliability to evaluate the internal consistency, and item analysis to test the discrimination validity of each item. Results: The results showed that the ICSR had accurate goodness-of-fit indices and the component reliability ranged from 0.42 to 0.83, indicating good reliability and validity. Conclusions: The ICSR is recommended for screening the self-help and medical-resource-seeking abilities of women with IC to aid in diagnosing IC and providing more precise medical treatments.

N-methyl-d-aspartate receptor hyperfunction contributes to d-serine-mediated renal insufficiency.

Glutamate N-methyl-d-aspartate receptor (NMDAR) hyperfunction is known to contribute to acute renal failure due to ischemia-reperfusion and endotoxemia. d-Serine is a coagonist for NMDAR activation, but whether NMDARs play a role in d-serine-mediated nephrotoxicity remains unclear. Here, we demonstrate that NMDAR blockade ameliorated d-serine-induced renal injury. In NMDAR-expressing LLC-PK1 cells, which were used as a proximal tubule model, d-serine but not l-serine induced cytotoxicity in a dose-dependent manner, which was abrogated by the selective NMDAR blockers MK-801 and AP-5. Time-dependent oxidative stress, evidenced by gradually increased superoxide and H2O2 production, was associated with d-serine-mediated cytotoxicity; these reactive oxygen species could be alleviated not only after NMDAR inhibition but also by NADPH oxidase (NOX) inhibition. Activation of protein kinase C (PKC)-δ and PKC-ζ is a downstream signal for NMDAR-mediated NOX activation because PKC inhibition diminishes the NOX activity that is induced by d-serine. Renal injury was further confirmed in male Wistar rats that intraperitoneally received d-serine but not l-serine. Peak changes in glucosuria, proteinuria, and urinary excretion of lactate dehydrogenase and malondialdehyde were found after 24 h of treatment. Persistent tubular damage was observed after 7 days of treatment. Cotreatment with the NMDAR blocker MK-801 for 24 h abolished d-serine-induced functional insufficiency and tubular damage. MK-801 attenuated renal superoxide formation by lowering NOX activity and protein upregulation of NOX4 but not NOX2. These results reveal that NMDAR hyperfunction underlies d-serine-induced renal injury via the effects of NOX4 on triggering oxidative stress.NEW & NOTEWORTHY Ionotropic N-methyl-d-aspartate receptors (NMDARs) are not only present in the nervous system but also expressed in the kidney. Overstimulation of renal NMDARs leads to oxidative stress via the signal pathway of calcium/protein kinase C/NADPH oxidase in d-serine-mediated tubular cell damage. Intervention of NMDAR blockade may prevent acute renal injury caused by d-serine.

CXCL5 Cytokine Is a Major Factor in Platelet-Rich Plasma's Preservation of Erectile Function in Rats After Bilateral Cavernous Nerve Injury.

BACKGROUND: The neuro-protective and tissue-protective properties of platelet-rich plasma (PRP) have been demonstrated through treating bilateral cavernous nerve (CN) injury in rats, although the underlying mechanisms have not been fully clarified. AIM: To determine factors released from PRP and explore their role in mediating preservation of erectile function (EF) in a rat model of CN injury. METHODS: Male Sprague-Dawley rats (aged 10 weeks) were used in this study. 6 rats were used to obtain blood for PRP and whole plasma preparation. We probed samples using a cytokine antibody array and performed enzyme-linked immunosorbent assay (ELISA). We determined the expression patterns of C-X-C motif chemokine ligand 5 (CXCL5) and receptors in the major pelvic ganglion (MPG) and corpus cavernosum via immunostaining. 32 rats were divided into 4 groups based on the type of injection received: (i) sham, (ii) vehicle, (iii) 400 µL of PRP, and (iv) 30 ng/kg of CXCL5. Groups 2-4 were subjected to bilateral CN crush (BCNC) injury. 4 weeks later, EF was assessed by CN electrostimulation, and CNs and penile tissue were collected for histological analysis. OUTCOME: Cytokine antibody array, ELISA, erectile response, and immunofluorescence staining readings. RESULTS: The PRP contained high levels of CXCL5. MPG neurons expressed CXCL5 and CXCR2. PRP intracavernous injection stabilized CXCR2 and increased CXCL5 expression in the MPG after BCNC, thus enhancing neuroprotection. CXCL5 injection improved BCNC-induced erectile dysfunction by preventing smooth muscle atrophy. CLINICAL IMPLICATIONS: The therapeutic efficacy of PRP in CN injury-induced erectile dysfunction may arise from the synergy among multiple biomolecules. Our study serves as a basis for future studies on PRP formulation to provide safe and effective medications for the maintenance of EF after radical prostatectomy in patients with prostate cancer. STRENGTHS & LIMITATIONS: A strength of our study is that our model was able to isolate the role of cytokines, specifically CXCL5, as part of the mechanism responsible for PRP's protective properties. However, the rat cytokine array provided limited experimental targets. The rats used were not at the age corresponding to prostate cancer patients in clinical settings. Our study did not explore CXCL5 blocking in the PRP group. Finally, the main protein quantification results by western blotting were hampered because of small tissue samples. CONCLUSIONS: This study provides evidence for the role of CXCL5 and CXCR2 as mediators of PRP effects in the preservation of EF after CN injury. Wu YN, Liao CH, Chen KC, et al. CXCL5 Cytokine Is a Major Factor in Platelet-Rich Plasma's Preservation of Erectile Function in Rats After Bilateral Cavernous Nerve Injury. J Sex Med 2021;18:698-710.

Adipose-Derived Stem Cells and Their Derived Microvesicles Ameliorate Detrusor Overactivity Secondary to Bilateral Partial Iliac Arterial Occlusion-Induced Bladder Ischemia.

(1) Background: We established a new bladder ischemia rat model through bilateral partial iliac arterial occlusion (BPAO) and investigated the therapeutic effect of adipose-derived stem cells (ADSCs) and ADSC-derived microvesicles (MVs); (2) Methods: The study included four groups: (1) sham, (2) BPAO, (3) BPAO + ADSCs, and (4) BPAO + ADSC-derived MVs. Female Wistar rats with BPAO were injected with ADSCs or ADSC-derived MVs through the femoral artery. Doppler flowmetry and real-time laser speckle contrast imaging were performed to quantify blood flow in the common iliac arteries and bladder microcirculation. A 24-h behavior study and transcystometrogram were conducted after 2 weeks. Bladder histology, immunostaining, and lipid peroxidation assay were performed. The expressions of P2X2, P2X3, M2, and M3 receptors and nerve growth factor (NGF) were evaluated; (3) Results: BPAO significantly reduced bladder microcirculation, intercontraction interval (ICI), and bladder volume and increased the amplitude of nonvoiding contraction, neutrophil infiltration, and malondialdehyde and NGF levels. ADSCs and ADSC-derived MVs significantly ameliorated these effects. The results of Western blot showed that the BPAO group exhibited the highest expression of M3 and P2X2 receptors. ADSCs significantly attenuated the expressions of M2 and P2X2 receptors. ADSC-derived MVs significantly attenuated the expressions of M3 and P2X2 receptors; (4) Conclusions: ADSCs and ADSC-derived MVs ameliorated the adverse effects of BPAO including bladder overactivity, bladder ischemia, and oxidative stress. Inflammation, muscarinic signaling, purinergic signaling, and NGF might be involved in the therapeutic mechanism.

B6 Mouse Strain: The Best Fit for LPS-Induced Interstitial Cystitis Model.

Interstitial cystitis (IC) is a chronic inflammatory disease characterized by bladder pain and increased urinary frequency. Although the C57BL/6J (B6) and FVB/NJ (FVB) mouse strains are commonly used as animal models for studies involving the urinary system, few reports have compared their lower urinary tract anatomy, despite the importance of such data. Our study aimed to characterize bladder function changes in FVB and B6 mouse strains with lipopolysaccharide (LPS)-induced IC, to understand mouse model-based bladder research. The bladder function parameters were measured by cystometrogram. Histological assay was examined by hematoxylin and eosin stain, Masson's trichrome stain, and immunofluorescence staining. Results indicated that the two strains in the control group exhibited different bladder structures and functions, with significant anatomical differences, including a larger bladder size in the FVB than in the B6 strain. Furthermore, cystometry tests revealed differences in bladder function pressure. LPS-treated B6 mice presented significant changes in peak pressure, with decreased intercontraction intervals; these results were similar to symptoms of IC in humans. Each strain displayed distinct characteristics, emphasizing the care required in choosing the appropriate strain for bladder-model studies. The results suggested that the B6 mouse strain is more suitable for IC models.

TRPV1 Hyperfunction Involved in Uremic Toxin Indoxyl Sulfate-Mediated Renal Tubular Damage.

Indoxyl sulfate (IS) is accumulated during severe renal insufficiency and known for its nephrotoxic properties. Transient receptor potential vanilloid 1 (TRPV1) is present in the kidney and acts as a renal sensor. However, the mechanism underlying IS-mediated renal tubular damage in view of TRPV1 is lacking. Here, we demonstrated that TRPV1 was expressed in tubular cells of Lilly Laboratories cell-porcine kidney 1 (LLC-PK1) and Madin-Darby canine kidney cells (MDCK). IS treatment in both cells exhibited tubular damage with increased LDH release and reduced cell viability in dose- and time-dependent manners. MDCK, however, was more vulnerable to IS. We, therefore, investigated MDCK cells to explore a more detailed mechanism. Interestingly, IS-induced tubular damage was markedly attenuated in the presence of selective TRPV1 blockers. IS showed no effect on TRPV1 expression but significantly increased arachidonate 12-lipoxygenase (ALOX12) protein, mRNA expression, and 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE) amounts in a dose-dependent manner, indicating that the ALOX12/12(S)-HETE pathway induced TRPV1 hyperfunction in IS-mediated tubulotoxicity. Blockade of ALOX12 by cinnamyl-3,4-dihydroxy-α-cyanocinnamate or baicalein attenuated the effects of IS. Since aryl hydrocarbon receptor (AhR) activation after IS binding is crucial in mediating cell death, here, we found that the AhR blockade not only ameliorated tubular damage but also attenuated ALOX12 expression and 12(S)-HETE production caused by IS. The uremic toxic adsorbent AST-120, however, showed little effect on ALOX12 and 12(S)-HETE, as well as IS-induced cell damage. These results clearly indicated that IS activated AhR and then upregulated ALOX12, and this induced endovanilloid 12(S)-HETE synthesis and contributed to TRPV1 hyperfunction in IS-treated tubular cells. Further study on TRPV1 may attenuate kidney susceptibility to the functional loss of end-stage kidney disease via IS.

Mirabegron escalation to 50 mg further improves daily urgency and urgency urinary incontinence in Asian patients with overactive bladder.

PURPOSE: To investigate the efficacy and safety of mirabegron dose escalation from 25 to 50 mg in Asian patients with overactive bladder (OAB). METHODS: A total of 242 patients (mean age: 67 years) with OAB were randomized to two groups: M25 (mirabegron 25 mg daily for 12 weeks) and M50 (mirabegron 25 mg daily for 4 weeks + 50 mg daily for 8 weeks). The primary endpoint was the percentage of patients without urgency or with a reduction of ≥2 in daily urgency episodes after treatment. Secondary endpoints included OAB symptom scores and other voiding parameters. Chi-squared and Wilcoxon signed-rank tests were used for data comparison. RESULTS: All OAB symptom scores in both groups improved significantly at 4 and 12 weeks. Both groups showed similar numbers of patients who reached the primary endpoint after treatment (M25: 64.6%, 42/65; M50: 64.9%, 50/77; p = 0.554). Patients in the M50 group with residual daily urgency or urgency urinary incontinence (UUI) episodes after 4 weeks of mirabegron 25 mg had a significantly higher rate of reduction in daily urgency episodes (60.9% vs. 34.5%, p = 0.034) and daily UUI episodes (87.5% vs. 37.5%, p = 0.021). Adverse event (AE) rates were similar between the groups. CONCLUSION: Mirabegron 25 mg for 12 weeks and mirabegron dose escalation from 25 to 50 mg exerted similar therapeutic effects. However, the dose escalation further improved the daily urgency and UUI episodes in patients with residual urgency or UUI after the initial treatment with mirabegron 25 mg.

Impact of novel techniques on minimally invasive adrenal surgery: trends and outcomes from a contemporary international large series in urology.

OBJECTIVE: To evaluate contemporary international trends in the implementation of minimally invasive adrenalectomy and to assess contemporary outcomes of different minimally invasive techniques performed at urologic centers worldwide. METHODS: A retrospective multinational multicenter study of patients who underwent minimally invasive adrenalectomy from 2008 to 2013 at 14 urology institutions worldwide was included in the analysis. Cases were categorized based on the minimally invasive adrenalectomy technique: conventional laparoscopy (CL), robot-assisted laparoscopy (RAL), laparoendoscopic single-site surgery (LESS), and mini-laparoscopy (ML). The rates of the four treatment modalities were determined according to the year of surgery, and a regression analysis was performed for trends in all surgical modalities. RESULTS: Overall, a total of 737 adrenalectomies were performed across participating institutions and included in this analysis: 337 CL (46 % of cases), 57 ML (8 %), 263 LESS (36 %), and 80 RA (11 %). Overall, 204 (28 %) operations were performed with a retroperitoneal approach. The overall number of adrenalectomies increased from 2008 to 2013 (p = 0.05). A transperitoneal approach was preferred in all but the ML group (p < 0.001). European centers mostly adopted CL and ML techniques, whereas those from Asia and South America reported the highest rate in LESS procedures, and RAL was adopted to larger extent in the USA. LESS had the fastest increase in utilization at 6 %/year. The rate of RAL procedures increased at slower rates (2.2 %/year), similar to ML (1.7 %/year). Limitations of this study are the retrospective design and the lack of a cost analysis. CONCLUSIONS: Several minimally invasive surgical techniques for the management of adrenal masses are successfully implemented in urology institutions worldwide. CL and LESS seem to represent the most commonly adopted techniques, whereas ML and RAL are growing at a slower rate. All the MIS techniques can be safely and effectively performed for a variety of adrenal disease.

Different number of intravesical onabotulinumtoxinA injections for patients with refractory detrusor overactivity do not affect treatment outcome: A prospective randomized comparative study.

AIMS: To examine the therapeutic effects and safety of different numbers of intravesical onabotulinumtoxinA (BoNT-A) injection for patients with detrusor overactivity (DO) refractory to antimuscarinics. METHODS: Patients with DO, at least one daily episode of urgency or urgency incontinence refractory to previous antimuscarinics were randomly assigned to receive 10, 20, or 40 intravesical BoNT-A injections 100 U in 10 mL in the bladder body. Treatment results were assessed with global response assessment GRA, OAB symptom score OAB-SS, urgency severity scale USS, patient perception of bladder condition PPBC, voiding diary, and urodynamic parameters. The primary endpoint was the comparison of the rates of successful treatment, which was defined as GRA ≥ 1 after treatment, between the groups. The secondary endpoints were the comparisons of the changes in the voiding diary, urodynamic parameters, individual AEs between the groups. RESULTS: Sixty-seven patients were randomized into three groups. Patients with GRA ≥ 1 at 1, 3, and 6 months after treatment were comparable between the groups. The average OAB-SS and USS and PPBC scores decreased whereas the average postvoid residual urine volume increased in all three groups. Changes in urodynamic and voiding diary parameters were also comparable between the groups. There were no significant differences in the rates of AEs and urinary tract infection after treatment. CONCLUSIONS: Different numbers of intravesical BoNT-A injections produced similar therapeutic and adverse effects. We therefore believe that 1 ml BoNT-A injections (10 U) at 10 sites are adequate to achieve an optimal therapeutic effect in OAB patients. Neurourol. Urodynam. 35:717-723, 2016. © 2015 Wiley Periodicals, Inc.

Optimizing a Male Reproductive Aging Mouse Model by D-Galactose Injection.

The d-galactose (d-gal)-injected animal model, which is typically established by administering consecutive subcutaneous d-gal injections to animals for approximately six or eight weeks, has been frequently used for aging research. In addition, this animal model has been demonstrated to accelerate aging in the brain, kidneys, liver and blood cells. However, studies on aging in male reproductive organs that have used this animal model remain few. Therefore, the current study aimed to optimize a model of male reproductive aging by administering d-gal injections to male mice and to determine the possible mechanism expediting senescence processes during spermatogenesis. In this study, C57Bl/6 mice were randomized into five groups (each containing 8-10 mice according to the daily intraperitoneal injection of vehicle control or 100 or 200 mg/kg dosages of d-gal for a period of six or eight weeks). First, mice subjected to d-gal injections for six or eight weeks demonstrated considerably decreased superoxide dismutase activity in the serum and testis lysates compared to those in the control group. The lipid peroxidation in testis also increased in the d-gal-injected groups. Furthermore, the d-gal-injected groups exhibited a decreased ratio of testis weight/body weight and sperm count compared to the control group. The percentages of both immotile sperm and abnormal sperm increased considerably in the d-gal-injected groups compared to those of the control group. To determine the genes influenced by the d-gal injection during murine spermatogenesis, a c-DNA microarray was conducted to compare testicular RNA samples between the treated groups and the control group. The d-gal-injected groups exhibited RNA transcripts of nine spermatogenesis-related genes (Cycl2, Hk1, Pltp, Utp3, Cabyr, Zpbp2, Speer2, Csnka2ip and Katnb1) that were up- or down-regulated by at least two-fold compared to the control group. Several of these genes are critical for forming sperm-head morphologies or maintaining nuclear integration (e.g., cylicin, basic protein of sperm head cytoskeleton 2 (Cylc2), casein kinase 2, alpha prime interacting protein (Csnka2ip) and katanin p80 (WD40-containing) subunit B1 (Katnb1)). These results indicate that d-gal-injected mice are suitable for investigating male reproductive aging.

5α-Reductase inhibitor is less effective in men with small prostate volume and low serum prostatic specific antigen level.

BACKGROUND/PURPOSE: Large total prostate volumes (TPVs) or high serum prostate-specific antigen (PSA) levels indicate high-risk clinical progression of benign prostatic hyperplasia. This prospective study investigated the treatment outcome of combined 5α-reductase inhibitor and α-blocker in patients with and without large TPVs or high PSA levels. METHODS: Men aged ≥ 45 years with International Prostate Symptom scores (IPSS) ≥ 8, TPV ≥ 20 mL, and maximum flow rate ≤ 15 mL/s received a combination therapy (dutasteride plus doxaben) for 2 years. Patients with baseline PSA ≥ 4 ng/mL underwent prostatic biopsy for excluding malignancy. The changes in the parameters from baseline to 24 months after combination therapy were compared in those with and without TPV ≥ 40 mL or PSA levels ≥ 1.5 ng/mL. RESULTS: A total of 285 patients (mean age 72 ± 9 years) completed the study. Combination therapy resulted in significant continuous improvement in IPSS, quality of life index, maximum flow rate, and postvoid residual (all p < 0.0001) regardless of baseline TPV or PSA levels. However, only patients with baseline TPV ≥ 40 mL had significant improvements in IPSS-storage subscore, voided volume, reduction in TPV, transitional zone index, and PSA levels. In addition, patients with baseline TPV < 40 mL and PSA < 1.5 ng/mL had neither a reduction in TPV nor a decrease in serum PSA level. CONCLUSION: A high TPV indicates more outlet resistance, whereas elevated serum PSA level reflects glandular proliferation. Thus, patients with TPV<40 mL and low PSA levels has less benefit from 5α-reductase inhibitor therapy. The therapeutic effect of combined treatment may arise mainly from the α-blocker in these patients.

Body mass index and age are predictors for symptom improvement after high-power laser vaporization for benign prostatic hyperplasia.

BACKGROUND/PURPOSE: To evaluate the effectiveness and safety of high-power 120W Greenlight HPS laser (HPS) and compare the results to transurethral resection of the prostate (TURP), and define a subgroup of patients who had better symptom score improvement after HPS. METHODS: One hundred and twenty-five patients who underwent surgery for benign prostatic hyperplasia (BPH) (61 HPS and 64 TURP) were retrospectively followed. Improvements of International Prostate Symptom Score (IPSS), quality of life score (QoL), maximum flow rate (Qmax) and post-void residual (PVR) were assessed at 4 weeks after the procedures. Potential covariates including age, body mass index (BMI), prostate volume (PV) and serum prostate-specific antigen (PSA) were defined and further subgroup analyses were utilized. RESULTS: The HPS group had a significantly higher education level, annual household income and larger prostate size. Compared with TURP, HPS resulted in comparable IPSS, QoL, Qmax and PVR improvements, but shorter hospitalization duration, serum hemoglobin loss and blood transfusion rate. Subgroup analyses showed that men in the HPS group were younger (age<76 years), had higher BMI (≥24kg/m(2)) and greater adjusted IPSS and QoL improvements than men in the TURP group. CONCLUSION: HPS offered adequate effectiveness for symptomatic BPH versus TURP and was advantageous with regard to operative safety. Patients who are younger and have higher BMI may achieve better improvements with HPS than with TURP. Further long-term follow-up study is warranted.

Diabetes mellitus does not affect the efficacy and safety of intravesical onabotulinumtoxinA injection in patients with refractory detrusor overactivity.

AIMS: To investigate the efficacy and safety of intravesical onabotulinumtoxinA injection in patients with diabetes mellitus (DM) and refractory detrusor overactivity (DO). METHODS: Forty-eight type 2 DM patients with refractory DO received intravesical 100 U onabotulinumtoxinA injection. Another 48 age-matched patients were randomly selected from a non-diabetic group as controls. Video-urodynamic studies were performed at baseline and were repeated 3 months after treatment. The treatment outcomes were graded on the basis of changes in the Patient's Perception of Bladder Condition (PPBC) and a PPBC decrease of 2 or more points was considered successful. Treatment-related adverse events including acute urinary retention, large post-voiding residual (PVR) volumes, straining to void, urinary tract infection, hematuria, and general weakness were recorded. RESULTS: The mean ages of the diabetic and non-diabetic patients were 73.1 ± 8.8 and 72.0 ± 9.3 (P = 0.552), respectively. The changes of urodynamic parameters were comparable between the two groups. Similar successful results were noted at the 6-month follow-up (DM, 56% vs. non-DM, 61%, P = 0.128). Diabetic patients had a significantly greater incidence of large PVR volumes (DM, 60.4% vs. non-DM, 33.3%; P = 0.007) and general weakness (DM, 10.4% vs. non-DM, 0%; P = 0.03) after treatment. Baseline urodynamic parameters in diabetic patients did not predict the occurrence of adverse events. No major complication was noted in either group. CONCLUSIONS: Intravesical onabotulinumtoxinA injection is a safe and effective treatment for DM patients with refractory DO. Patients with DM should be informed of the increased risk of large PVR before initiation of treatment.

Chlorogenic Acid Intravesical Therapy Changes Acute Voiding Behavior of Systemic Lipopolysaccharide Inflammation-Induced Cystitis Bladder in Mice.

This study explores the potential efficacy of chlorogenic acid (CGA) in mitigating lipopolysaccharide (LPS)-induced cystitis in a mice model. C57BL/6J mice were divided into four groups: normal control (NC), LPS, LPS + low CGA, and LPS + high CGA. Evaluation methods included cystometrogram (CMG), histopathological, western blot, and immunohistological analysis. In the LPS group, CMG revealed abnormal voiding behavior with increased micturition pressure, voided volume (VV), and decreased voided frequency. Low CGA treatment in LPS mice demonstrated improved micturition pressure and inter-contraction intervals (ICI). However, high CGA treatment exhibited prolonged ICI and increased VV, suggesting potential adverse effects. Histological analysis of LPS-treated mice displayed bladder inflammation and interstitial edema. Low CGA treatment reduced interstitial edema and bladder inflammation, confirmed by Masson's trichrome staining. Western blotting revealed increased cytokeratin 20 (K20) expression in the low CGA group, indicating structural abnormalities in the bladder umbrella layer after LPS administration. In conclusion, low CGA treatment positively impacted voiding behavior and decreased bladder edema and inflammation in the LPS-induced cystitis mice model, suggesting its potential as a supplement for inflammation cystitis prevention. However, high CGA treatment exhibited adverse effects, emphasizing the importance of dosage considerations in therapeutic applications.

Predicting Clinically Significant Prostate Cancer Using Urine Metabolomics via Liquid Chromatography Mass Spectrometry.

PURPOSE: Biomarkers predicting clinically significant prostate cancer (sPC) before biopsy are currently lacking. This study aimed to develop a non-invasive urine test to predict sPC in at-risk men using urinary metabolomic profiles. MATERIALS AND METHODS: Urine samples from 934 at-risk subjects and 268 treatment-naïve PC patients were subjected to liquid chromatography/mass spectrophotometry (LC-MS)-based metabolomics profiling using both C18 and hydrophilic interaction liquid chromatography (HILIC) column analyses. Four models were constructed (training cohort [n=647]) and validated (validation cohort [n=344]) for different purposes. Model I differentiates PC from benign cases. Models II, III, and a Gleason score model (model GS) predict sPC that is defined as National Comprehensive Cancer Network (NCCN)-categorized favorable-intermediate risk group or higher (Model II), unfavorable-intermediate risk group or higher (Model III), and GS ≥7 PC (model GS), respectively. The metabolomic panels and predicting models were constructed using logistic regression and Akaike information criterion. RESULTS: The best metabolomic panels from the HILIC column include 25, 27, 28 and 26 metabolites in Models I, II, III, and GS, respectively, with area under the curve (AUC) values ranging between 0.82 and 0.91 in the training cohort and between 0.77 and 0.86 in the validation cohort. The combination of the metabolomic panels and five baseline clinical factors that include serum prostate-specific antigen, age, family history of PC, previously negative biopsy, and abnormal digital rectal examination results significantly increased AUCs (range 0.88-0.91). At 90% sensitivity (validation cohort), 33%, 34%, 41%, and 36% of unnecessary biopsies were avoided in Models I, II, III, and GS, respectively. The above results were successfully validated using LC-MS with the C18 column. CONCLUSIONS: Urinary metabolomic profiles with baseline clinical factors may accurately predict sPC in men with elevated risk before biopsy.