Abstract

Objective: To prospectively investigate the association of endothelial nitric oxide synthase (eNOS) G894T gene polymorphism with responsiveness to a selective α1-blocker in men with benign prostatic hyperplasia related lower urinary tract symptoms (BPH/LUTS), as nitric oxide has recently gained increasing recognition as an important neurotransmitter of functions in the lower urinary tract.

Patients and Methods: In all, 136 men with BPH/LUTSwere recruited from urology outpatient clinics in a university hospital. Oral therapy with doxazosin gastrointestinal therapeutic system (CITS) 4 mg once-daily was given for 12 weeks. The drug efficacy was assessed by the changes from baseline in the total International Prostate Symptom Score (IPSS), maximum urinary flow rate (Q_max) and post-void residual urine volume (PVR) at 12 weeks of treatment. The'responders'to doxazosin GITS were defined as those who had a total IPSS decrease of >4 points from baseline.eNOS G894T polymorphisms were determined using the polymerase chain reaction-restriction fragment length polymorphism method.

Results: Patients had statistically significant improvements in total IPSS, quality of life score and Q_max(P < 0.01) after a 12-week period of treatment. Using multiple logistic regression analysis adjusted for age and IPSS, our results showed that being a eNOS 894T allele carrier was an independent risk factor for being a drug non-responder (p=0.03, odds ratio 4.19). Moreover, a decreased responder rate (p=0.0l), as well as the lower improvements in IPSS (p=0.02) and Qmax (p=0.03), were significantly associated with increment in the T allele number.

Conclusions: The presence of the eNOS 894T allele had a significantly negative impact on responsiveness to a selective α₁-blocker in BPH/LUT treatment, suggesting that eNOS G894T gene polymorphisms may be a genetic susceptibility factor for α₁-blocker efficacy in men with BPH/LUTS.

This study aimed to investigate differences in healthcare service utilization between patients with and those without benign prostatic hyperplasia (BPH) using Taiwan’s National Health Insurance population-based database.

A total of 7413 patients with BPH and 7413 age-matched patients without BPH were included. The outcome variable was 1-year utilization of healthcare services including the number of outpatient visits, inpatient days, and the costs of outpatient and inpatient treatments. In addition, we separated healthcare services into urology services and nonurology services for analysis.

We found that as to the utilization of outpatient urological services, patients with BPH had more outpatient services (7.84 vs 0.52, P<0.001), higher outpatient costs (US$372 vs US$34, P<0.001), a longer length of inpatient stay (0.55 vs 0.11, P<0.001), higher in-patients costs (US$149 vs US$32, P<0.001), and higher total costs (US$521 vs US$67, P<0.001) than the comparison group. As for nonurological services, patients with BPH also had more outpatient services (49.11 vs 24.79, P<0.001), higher outpatient costs (US$1794 vs US$1014, P<0.001), a longer length of in-patient stay (3.72 vs 2.04, P<0.001), higher inpatient costs (US$874 vs US$486, P<0.001), and higher total costs (US$2668 vs US$1500, P<0.001) compared to comparison patients. We also found that the average total cost was about 2-fold greater for patients with BPH than comparison patients.

We concluded that patients with BPH had higher healthcare utilization than comparison patients without BPH.

Abstract

This study investigated the effect of resistant maltodextrin (RMD) on reproduction in streptozotocin (STZ)-nicotinamide induced type 2 diabetic male rats. Forty male rats were induced with diabetes by a single intraperitoneal injection of STZ (50mg/kg^-1) and nicotinamide (100mg/kg^-1). Five groups were analyzed in total: normal, diabetic rats without RMD, diabetic rats with RMD 1.2g per 100g diet (1×), with RMD 2.4g per 100g (2×), and with RMD 6.0g per 100g (5×). The groups of diabetic rats with the RMD supplement, compared to those without supplement, showed improved plasma glucose control, attenuated insulin resistance and recovery of testosterone level & spermatogenesis stage. The STZ-nicotinamide induced diabetes mellitus (DM) caused a significant reduction in serum testosterone, testis androgen receptor (AR), steroidogenic acute regulatory protein (StAR) and 3 β-hydroxysteroid dehydrogenase (3 β-HSD) protein, but a statistical recovery in each of these was observed in the 5× group. TUNEL-positive cells were observed in the diabetic without RMD group and RMD treatment reduced apoptotic germ cells. The expression of Bax/Bcl2 was induced in the diabetic group and also significantly reduced in the 5× group. Dietary RMD may improve metabolic control in STZ-nicotinamide induced diabetic rats and attenuate hyperglycemia-related impaired male reproduction and testicular function.

There is an unmet need for treatment of erectile dysfunction resulting from radical prostatectomy and cavernous nerve (CN) injury. Given the neuroprotective properties of docosahexaenoic acid (DHA), we investigated its effect on penile functional and structural recovery in a rat model of bilateral cavernous nerve injury. Rats were subject to CN injury and received intraperitoneal administration of either vehicle or a DHA nanoemulsion (nano-DHA) at 10, 50, or 250 ug/kg. Functional testing and histological analyses were performed at 28 days post-injury. The maximum intracavernosal pressure (ICP) and other measures of erectile function were significantly higher in the nano-DHA groups than in the vehicle group (p < 0.05). The ratio of area of expression of neuronal nitric oxide synthase (nNOS)/β-III tubulin, numbers of axon and smooth muscle cell content were significantly higher in the 50 ug/kg nano-DHA group than in the vehicle group (p < 0.05). A qualitative increase in the smooth muscle cells/ collagen ratio and decrease in apoptosis was observed in the nano-DHA groups relative to the vehicle group: however, these differences were not statistically significant. Our data demonstrate that nano-DHA, particularly the 50 ug/kg regimen, improves erectile function after bilateral CN injury in rats by neuroprotection and other anti-fibrotic and anti-apoptotic mechanisms.

We investigated and evaluated the mechanisms of erectile dysfunction (ED) in a rat model of long-term ketamine administration.

Adult male Sprague-Dawley rats (n=32) were divided into four groups: namely the control group receiving daily intraperitoneal injection of saline, 1-month, 2-month and 3-month groups receiving daily intraperitoneal injection of ketamine (100 mg/kg/day) for 1, 2 and 3 month respectively. After treatment, animals underwent an erectile response protocol to assess intracavernosal pressure (ICP). Smooth muscle content was evaluated. Neuronal nitric oxide synthase (nNos), inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) expression were assessed using immunostaining assay. Ketamine-induced apoptosis was analyzed using TUNEL assay.

Long-term ketamine administration caused significantly decreased erectile responses as measured by ICP. Smooth muscle content was significantly decreased in the ketamine-treated rats for 3 months. In the erectile tissue, ketamine administration significantly reduced nNOS expression and increased iNOS content compared with controls, whereas eNOS expression was not altered. Ketamine induced apoptosis in corpus cavernosum.

The present study demonstrates that long-term ketamine administration led to erectile dysfunction in rat. The molecular mechanisms of ketamine-induced ED involved the increased apoptosis and up-regulated iNOS expression incorporating with loss of corporal smooth muscle content and reduced nNOS expression in cavernous nerve.