The Association of eNOS G894T Gene Polymorphism with Responsiveness to a
Selective α1-blocker in Men with BPH Related Lower Urinary Tract Symptoms
Yung-Chin Lee1,2, Yung-Shun Juan 1,2,3, Chia-Chu Liu 1,2,4, Bo-Ying Bao 5,6,7, Chii-Jye Wang 1,2,,
Wen-Jeng Wu1,2, Chun-Nung Huang1,2, and Shu-Pin Huang 1,2,8 1Department of Urology, 2Department of Urology, Faculty of Medicine,
Kaohsiung Medical University, 3Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, 4Department of Health, Executive Yuan, Pingtung Hospital, Pingtung, 5Department of Pharmacy, 6Sex Hormone Research Center, China, Medical University Hospital, 7Department of Nursing, Asia University, Taichung and 8Graduate Institute of Medicine,
College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
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 (Qmax) 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 Qmax(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.
男性學論文獎 臨床組 第二名
Asian Journal of Andrology 2016 18, 1-4 doi: 10.4103/1008-682X.167718
Healthcare Utilization and Costs in Patients with Benign
Prostatic Hyperplasia : A Population-based Study
Shiu-Dong Chung1-3*, Ya-Mei Tzeng4*, Herng-Ching Lin3, Chao-Yuan Huang5,6 1Division of Urology, Department of Surgery, Far Eastern Memorial Hospital,
New Taipei City, Taiwan 2School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan 3
Sleep Research Center, Taipei Medical University Hospital, Taipei, Taiwan 4Graduate Institute of Life Science, National Defense Medical Center, Taipei, Taiwan 5Department of Urology, National Taiwan University Hospital,College of Medicine National Taiwan University, Taipei, Taiwan 6School of Public Health, Taipei Medical University, Taipei, Taiwan
*These two authors contributed equally to this work
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.
Dietary Resistant Maltodextrin Ameliorates Testicular Function and
Spermatogenesis in Streptozotocin-nicotinamide-induced Diabetic Rats
Chin-Yu Liu1, Yu-Juei Hsu2,Yi-Wen Eve Chien3, Tai-Lung Cha4 and Chih-Wei Tsao4 1Department of Nutritional Science, Fu Jen Catholic University, New Taipei City, Taiwan 2Division of Nephrology, Department of Medicine, Tri-Service General Hospital,
National Defense Medical Center, Taipei, Taiwan 3School of Nutrition and Health Sciences, Taipei Medical University, Taipei, Taiwan 4Division of Urology, Department of Surgery, Tri-Service General Hospital,
National Defense Medical Center, Taipei, Taiwan
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.
江萬煊教授傑出研究論文獎
Scientific Reports,6:33040, doi: 10.1038
Neuroprotective Effect of Docosahexaenoic Acid Nanoemulsion on Erectile Function in a Rat Model of Bilateral Cavernous Nerve Injury
Chun-Hou Liao1,2,3*, Yi-No Wu3,4,*, Bin-Huei Chen4,5, Ying-Hung Lin4,
Hsiu-O Ho6 & Han-Sun Chiang1,2,3,4 1Division of Urology, Department of Surgery, Cardinal Tien Hospital, New Taipei City, Taiwan 2
School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan 3
PhD Program in Nutrition & Food Science, Fu Jen Catholic University, New Taipei City, Taiwan
4
Graduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University,
New Taipei City, Taiwan 5
Department of Food Science, Fu Jen Catholic University, New Taipei City, Taiwan 6
School of Pharmacy, Taipei Medical University, Taipei, Taiwan
*These authors contributed equally to this work
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.
臺灣楓城泌尿學會男性學論文獎
Oncotarget, Advance Publication 2016
Long-term Administration of Ketamine Induces Erectile Dysfunction by
Decreasing Neuronal Nitric Oxide Synthase on Cavernous Nerve and
Increasing Corporal Smooth Muscle Cell Apoptosis in Rats
Hung-Sheng Shang1,2*, Yi-No Wu3*, Chun-Hou Liao4,5, Tzong-Shi Chiueh2,
Yuh-Feng Lin1,7,8, Han-Sun Chiang3,4,6 1Graduate Institute of Clinical of Medicine, College of Medicine,
Taipei Medical University, New Taipei City, Taiwan 2Division of Clinical Pathology, Department of Pathology, Tri-Service General Hospital,
National Defense Medical Center, Taipei, Taiwan 3Graduate Institute of Basic Medicine, Fu Jen Catholic University, New Taipei City, Taiwan 4Division of Urology, Department of Surgery, Cardinal Tien Hospital, Taipei City, Taiwan 5College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan 6Department of Urology, Taipei Medical University Hospital, Taipei, Taiwan 7Division of Nephrology, Department of Medicine,
Shuang Ho Hospital, School of Medicine, College of Medicine,
Taipei Medical University, New Taipei City, Taiwan 8Division of Nephrology, Department of Medicine, Tri-Service General Hospital,
National Defense Medical Center, Taipei, Taiwan
*These authors have contributed equally to this work
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.