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   2016| September-October  | Volume 18 | Issue 5  
    Online since August 11, 2016

 
 
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LETTERS TO THE EDITOR
Intracytoplasmic sperm injection outcomes in Chinese men with multiple morphological abnormalities of sperm flagella
Shen-Min Yang, Xiao-Yu Yang, Yang Ding, Hong Li, Wei Wang, Jia-Yin Liu, Duan-Gai Wen
September-October 2016, 18(5):809-811
DOI:10.4103/1008-682X.167722  PMID:26620459
  20,764 440 4
ORIGINAL ARTICLES
Circumcision with "no-flip Shang Ring" and "Dorsal Slit" methods for adult males: a single-centered, prospective, clinical study
Jun-Hao Lei, Liang-Ren Liu, Qiang Wei, Wen-Ben Xue, Tu-Run Song, Shi-Bing Yan, Lu Yang, Ping Han, Yu-Chun Zhu
September-October 2016, 18(5):798-802
DOI:10.4103/1008-682X.157544  PMID:26585694
This paper was aimed to compare the clinical effectiveness and safety of adult male circumcision using the Shang Ring (SR) with the no-flip technique compared with Dorsal Slit (DS) surgical method. A single-centered, prospective study was conducted at the West China Hospital, where patients were circumcised using the no-flip SR (n = 408) or the DS (n = 94) procedure. The adverse events (AEs) and satisfaction were recorded for both groups, and ring-removal time and percentage of delayed removals were recorded for the SR group. Finally, complete follow-up data were collected for 76.1% of patients (SR: n = 306; DS: n = 76). The average ring-removal time for the SR group was 17.62 ± 6.30 days. The operation time (P < 0.001), pain scores during the procedure (P < 0.001) and at 24 h postoperatively (P < 0.001), bleeding (P = 0.001), infection (P = 0.034), and satisfaction with penile appearance (P < 0.001) in the SR group were superior to those in the DS group. After two postoperative weeks, the percentage of patients with edema in the SR group (P = 0.029) was higher but no differences were found at 4 weeks (P = 0.185) between the two groups. In conclusions, the no-flip SR method was found to be superior to the DS method for its short operation time (<5 min), involving less pain, bleeding, infection, and resulting in a satisfactory appearance. However, the time for recovery from edema took longer, and patients may wear device for 2-3 weeks after the procedure.
  10,906 478 5
Patient satisfaction and penile morphology changes with postoperative penile rehabilitation 2 years after Coloplast Titan prosthesis
Michael B Pryor, Rafael Carrion, Run Wang, Gerard Henry
September-October 2016, 18(5):754-758
DOI:10.4103/1008-682X.163266  PMID:26459782
A common complaint after inflatable penile prosthesis surgery is reduced penile length. We previously reported how using the Coloplast Titan inflatable penile prosthesis with aggressive new length measurement technique (NLMT) coupled with postoperative IPP rehabilitation of the implant for 1-year helped to improve patient satisfaction and erectile penile measurements. This is a 2 years follow-up of a prospective, three-center, study of 40 patients who underwent Titan prosthesis placement, with new length measurement technique for erectile dysfunction. Patient instructions were to inflate daily for 6 months and then inflate maximally for 1-2 h daily for 6-24 months. Fifteen penile measurements were taken before and immediately after surgery and at follow-up visits. Measurement changes were improved at 24 months as compared to immediately postoperative and at 12 months. 67.8% of subjects were satisfied with their length at 2 years, and 77% had perceived penile length that was longer (30.8%) or the same (46.2%) as prior to the surgery. 64.3% and 17.9% of subjects had increased and unchanged satisfaction, respectively, with penile length as compared to prior to penile implant surgery. All but one subject (96.5%) was satisfied with the overall function of his implant. This study suggests using the Coloplast Titan with aggressive cylinder sizing, and a postoperative penile rehabilitation inflation protocol can optimize patient satisfaction and erectile penile measurements at 2 years postimplant.
  10,176 588 16
INVITED REVIEW
A sting in the tail: the N-terminal domain of the androgen receptor as a drug target
Amy E Monaghan, Iain J McEwan
September-October 2016, 18(5):687-694
DOI:10.4103/1008-682X.181081  PMID:27212126
The role of androgen receptor (AR) in the initiation and progression of prostate cancer (PCa) is well established. Competitive inhibition of the AR ligand-binding domain (LBD) has been the staple of antiandrogen therapies employed to combat the disease in recent years. However, their efficacy has often been limited by the emergence of resistance, mediated through point mutations, and receptor truncations. As a result, the prognosis for patients with malignant castrate resistant disease remains poor. The amino-terminal domain (NTD) of the AR has been shown to be critical for AR function. Its modular activation function (AF-1) is important for both gene regulation and participation in protein-protein interactions. However, due to the intrinsically disordered structure of the domain, its potential as a candidate for therapeutic intervention has been dismissed in the past. The recent emergence of the small molecule EPI-001 has provided evidence that AR-NTD can be targeted therapeutically, independent of the LBD. Targeting of AR-NTD has the potential to disrupt multiple intermolecular interactions between AR and its coregulatory binding partners, in addition to intramolecular cross-talk between the domains of the AR. Therapeutics targeting these protein-protein interactions or NTD directly should also have efficacy against emerging AR splice variants which may play a role in PCa progression. This review will discuss the role of intrinsic disorder in AR function and illustrate how emerging therapies might target NTD in PCa.
  6,679 1,042 20
REVIEW
Clinical and preclinical treatment of urologic diseases with phosphodiesterase isoenzymes 5 inhibitors: an update
Wen-Hao Zhang, Xin-Hua Zhang
September-October 2016, 18(5):723-731
DOI:10.4103/1008-682X.167721  PMID:26620458
Phosphodiesterase isoenzymes 5 inhibitors (PDE5-Is) are the first-line therapy for erectile dysfunction (ED). The constant discoveries of nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) cell-signaling pathway for smooth muscle (SM) control in other urogenital tracts (UGTs) make PDE5-Is promising pharmacologic agents against other benign urological diseases. This article reviews the literature and contains some previously unpublished data about characterizations and activities of PDE5 and its inhibitors in treating urological disorders. Scientific discoveries have improved our understanding of cell-signaling pathway in NO/cGMP-mediated SM relaxation in UGTs. Moreover, the clinical applications of PDE5-Is have been widely recognized. On-demand PDE5-Is are efficacious for most cases of ED, while daily-dosing and combination with testosterone are recommended for refractory cases. Soluble guanylate cyclase (sGC) stimulators also have promising role in the management of severe ED conditions. PDE5-Is are also the first rehabilitation strategy for postoperation or postradiotherapy ED for prostate cancer patients. PDE5-Is, especially combined with α-adrenoceptor antagonists, are very effective for benign prostatic hyperplasia (BPH) except on maximum urinary flow rate (Q max ) with tadalafil recently proved for BPH with/without ED. Furthermore, PDE5-Is are currently under various phases of clinical or preclinical researches with promising potential for other urinary and genital illnesses, such as priapism, premature ejaculation, urinary tract calculi, overactive bladder, Peyronie's disease, and female sexual dysfunction. Inhibition of PDE5 is expected to be an effective strategy in treating benign urological diseases. However, further clinical studies and basic researches investigating mechanisms of PDE5-Is in disorders of UGTs are required.
  6,893 806 8
ORIGINAL ARTICLES
Augmented reality assisted surgery: a urologic training tool
Ryan M Dickey, Neel Srikishen, Larry I Lipshultz, Philippe E Spiess, Rafael E Carrion, Tariq S Hakky
September-October 2016, 18(5):732-734
DOI:10.4103/1008-682X.166436  PMID:26620455
Augmented reality is widely used in aeronautics and is a developing concept within surgery. In this pilot study, we developed an application for use on Google Glass ® optical head-mounted display to train urology residents in how to place an inflatable penile prosthesis. We use the phrase Augmented Reality Assisted Surgery to describe this novel application of augmented reality in the setting of surgery. The application demonstrates the steps of the surgical procedure of inflatable penile prosthesis placement. It also contains software that allows for detection of interest points using a camera feed from the optical head-mounted display to enable faculty to interact with residents during placement of the penile prosthesis. Urology trainees and faculty who volunteered to take part in the study were given time to experience the technology in the operative or perioperative setting and asked to complete a feedback survey. From 30 total participants using a 10-point scale, educational usefulness was rated 8.6, ease of navigation was rated 7.6, likelihood to use was rated 7.4, and distraction in operating room was rated 4.9. When stratified between trainees and faculty, trainees found the technology more educationally useful, and less distracting. Overall, 81% of the participants want this technology in their residency program, and 93% see this technology in the operating room in the future. Further development of this technology is warranted before full release, and further studies are necessary to better characterize the effectiveness of Augmented Reality Assisted Surgery in urologic surgical training.
  6,121 774 29
Proteomic analysis of mature and immature ejaculated spermatozoa from fertile men
Zhihong Cui, Rakesh Sharma, Ashok Agarwal
September-October 2016, 18(5):735-746
DOI:10.4103/1008-682X.164924  PMID:26510506
Dysfunctional spermatozoa maturation is the main reason for the decrease in sperm motility and morphology in infertile men. Ejaculated spermatozoa from healthy fertile men were separated into four fractions using three-layer density gradient. Proteins were extracted and bands were digested on a LTQ-Orbitrap Elite hybrid mass spectrometer system. Functional annotations of proteins were obtained using bioinformatics tools and pathway databases. Western blotting was performed to verify the expression levels of the proteins of interest. 1469 proteins were identified in four fractions of spermatozoa. The number of detected proteins decreased according to the maturation level of spermatozoa. During spermatozoa maturation, proteins involved in gamete generation, cell motility, energy metabolism and oxidative phosphorylation processes showed increasing expression levels and those involved in protein biosynthesis, protein transport, protein ubiquitination, and response to oxidative stress processes showed decreasing expression levels. We validated four proteins (HSP 70 1A, clusterin, tektin 2 and tektin 3) by Western blotting. The study shows protein markers that may provide insight into the ejaculated spermatozoa proteins in different stages of sperm maturation that may be altered or modified in infertile men.
  4,972 731 20
INVITED REVIEW
Prostate-associated gene 4 (PAGE4), an intrinsically disordered cancer/testis antigen, is a novel therapeutic target for prostate cancer
Prakash Kulkarni, A Keith Dunker, Keith Weninger, John Orban
September-October 2016, 18(5):695-703
DOI:10.4103/1008-682X.181818  PMID:27270343
Prostate-associated gene 4 (PAGE4) is a remarkably prostate-specific Cancer/Testis Antigen that is highly upregulated in the human fetal prostate and its diseased states but not in the adult normal gland. PAGE4 is an intrinsically disordered protein (IDP) that functions as a stress-response protein to suppress reactive oxygen species as well as prevent DNA damage. In addition, PAGE4 is also a transcriptional regulator that potentiates transactivation by the oncogene c-Jun. c-Jun forms the AP-1 complex by heterodimerizing with members of the Fos family and plays an important role in the development and pathology of the prostate gland, underscoring the importance of the PAGE4/c-Jun interaction. HIPK1, also a component of the stress-response pathway, phosphorylates PAGE4 at T51 which is critical for its transcriptional activity. Phosphorylation induces conformational and dynamic switching in the PAGE4 ensemble leading to a new cellular function. Finally, bioinformatics evidence suggests that the PAGE4 mRNA could be alternatively spliced resulting in four potential isoforms of the polypeptide alluding to the possibility of a range of conformational ensembles with latent functions. Considered together, the data suggest that PAGE4 may represent the first molecular link between stress and prostate cancer (PCa). Thus, pharmacologically targeting PAGE4 may be a novel opportunity for treating and managing patients with PCa, especially patients with low-risk disease.
  4,973 562 11
INVITED ORIGINAL ARTICLE
Unfoldomics of prostate cancer: on the abundance and roles of intrinsically disordered proteins in prostate cancer
Kevin S Landau, Insung Na, Ryan O Schenck, Vladimir N Uversky
September-October 2016, 18(5):662-672
DOI:10.4103/1008-682X.184999  PMID:27453073
Prostatic diseases such as prostate cancer and benign prostatic hyperplasia are highly prevalent among men. The number of studies focused on the abundance and roles of intrinsically disordered proteins in prostate cancer is rather limited. The goal of this study is to analyze the prevalence and degree of disorder in proteins that were previously associated with the prostate cancer pathogenesis and to compare these proteins to the entire human proteome. The analysis of these datasets provides means for drawing conclusions on the roles of disordered proteins in this common male disease. We also hope that the results of our analysis can potentially lead to future experimental studies of these proteins to find novel pathways associated with this disease.
  4,476 571 5
INVITED REVIEW
Phenotypic plasticity in prostate cancer: role of intrinsically disordered proteins
Steven M Mooney, Mohit Kumar Jolly, Herbert Levine, Prakash Kulkarni
September-October 2016, 18(5):704-710
DOI:10.4103/1008-682X.183570  PMID:27427552
A striking characteristic of cancer cells is their remarkable phenotypic plasticity, which is the ability to switch states or phenotypes in response to environmental fluctuations. Phenotypic changes such as a partial or complete epithelial to mesenchymal transition (EMT) that play important roles in their survival and proliferation, and development of resistance to therapeutic treatments, are widely believed to arise due to somatic mutations in the genome. However, there is a growing concern that such a deterministic view is not entirely consistent with multiple lines of evidence, which indicate that stochasticity may also play an important role in driving phenotypic plasticity. Here, we discuss how stochasticity in protein interaction networks (PINs) may play a key role in determining phenotypic plasticity in prostate cancer (PCa). Specifically, we point out that the key players driving transitions among different phenotypes (epithelial, mesenchymal, and hybrid epithelial/mesenchymal), including ZEB1, SNAI1, OVOL1, and OVOL2, are intrinsically disordered proteins (IDPs) and discuss how plasticity at the molecular level may contribute to stochasticity in phenotypic switching by rewiring PINs. We conclude by suggesting that targeting IDPs implicated in EMT in PCa may be a new strategy to gain additional insights and develop novel treatments for this disease, which is the most common form of cancer in adult men.
  4,311 651 39
Plastins regulate ectoplasmic specialization via its actin bundling activity on microfilaments in the rat testis
Nan Li, Chris KC Wong, C Yan Cheng
September-October 2016, 18(5):716-722
DOI:10.4103/1008-682X.166583  PMID:26608945
Plastins are a family of actin binding proteins (ABPs) known to cross-link actin microfilaments in mammalian cells, creating actin microfilament bundles necessary to confer cell polarity and cell shape. Plastins also support cell movement in response to changes in environment, involved in cell/tissue growth and development. They also confer plasticity to cells and tissues in response to infection or other pathological conditions (e.g., inflammation). In the testis, the cell-cell anchoring junction unique to the testis that is found at the Sertoli cell-cell interface at the blood-testis barrier (BTB) and at the Sertoli-spermatid (e.g., 8-19 spermatids in the rat testis) is the basal and the apical ectoplasmic specialization (ES), respectively. The ES is an F-actin-rich anchoring junction constituted most notably by actin microfilament bundles. A recent report using RNAi that specifically knocks down plastin 3 has yielded some insightful information regarding the mechanism by which plastin 3 regulates the status of actin microfilament bundles at the ES via its intrinsic actin filament bundling activity. Herein, we provide a brief review on the role of plastins in the testis in light of this report, which together with recent findings in the field, we propose a likely model by which plastins regulate ES function during the epithelial cycle of spermatogenesis via their intrinsic activity on actin microfilament organization in the rat testis.
  4,426 520 5
ORIGINAL ARTICLES
Identification of late-onset hypogonadism in middle-aged and elderly men from a community of China
Zhi-Yong Liu, Ren-Yuan Zhou, Xin Lu, Qin-Song Zeng, Hui-Qing Wang, Zheng Li, Ying-Hao Sun
September-October 2016, 18(5):747-753
DOI:10.4103/1008-682X.160883  PMID:26354142
In this study, we investigated the essential criteria for late-onset hypogonadism (LOH) syndrome based on the presence of symptoms associated with low testosterone levels in Han Chinese men. Blood tests for total testosterone (TT) and sex hormone-binding globulin (SHBG) were performed, and the aging male symptoms (AMS) questionnaire was conducted in a randomly selected cohort composed of 944 Chinese men aged 40 to 79 years from nine urban communities. Three sexual symptoms (decreased ability/frequency of sexual activity, decreased number of morning erections, and decreased libido) were confirmed to be related to the total and free testosterone levels. The thresholds for TT were approximately 12.55 nmol l−1 for a decreased ability/frequency to perform sex, 12.55 nmol l−1 for decreased frequency of morning erections, and 14.35 nmol l−1 for decreased sexual desire. The calculated free testosterone (CFT) thresholds for these three sexual symptoms were 281.14, 264.90, and 287.21 pmol l−1 , respectively. TT <13.21 nmol l−1 (OR = 1.4, 95%CI: 1.0-1.9, P = 0.037) or CFT <268.89 pmol l−1 (OR = 1.5, 95%CI: 1.1-20, P = 0.020) was associated with an increase in the aforementioned three sexual symptoms. The prevalence of LOH was 9.1% under the criteria, including all three sexual symptoms with TT levels <13.21 nmol l−1 and CFT levels <268.89 pmol l−1 . Our results may improve the diagnostic accuracy of LOH in older men.
  4,338 483 11
INVITED REVIEW
Steroid hormone receptors and prostate cancer: role of structural dynamics in therapeutic targeting
Raj Kumar
September-October 2016, 18(5):682-686
DOI:10.4103/1008-682X.183380  PMID:27364545
Steroid hormone receptors (SHRs) act in cell type- and gene-specific manner through interactions with coregulatory proteins to regulate numerous physiological and pathological processes at the level of gene regulation. Binding of steroid receptor modulator (SRM) ligand leads to allosteric changes in SHR to exert positive or negative effects on the expression of target genes. Due, in part, to the fact that current SRMs generally target ligand binding domain (LBD)/AF2 and neglect intrinsically disordered (ID) N-terminal domain (NTD)/AF1, clinically relevant SRMs lack selectivity and are also prone to the development of resistance over time. Therefore, to maximize the efficacy of SHR-based therapeutics, the possibility of developing unique modulators that act to control AF1 activity must be considered. Recent studies targeting androgen receptor's (AR's) ID AF1 domain for the castration-resistant prostate cancer has provided the possibility of therapeutically targeting ID NTD/AF1 surfaces by allosteric modulations to achieve desired effects. In this review article, we discuss how inter- and intra- molecular allosteric regulations controlled by AR's structural flexibility and dynamics particularly the ID NTD/AF1 is an emerging area of investigation, which could be exploited for drug development and therapeutic targeting of prostate cancer.
  4,029 635 10
ORIGINAL ARTICLES
Genetic effects on serum testosterone and sex hormone-binding globulin in men: a Korean twin and family study
Joohon Sung, Yun-Mi Song
September-October 2016, 18(5):786-790
DOI:10.4103/1008-682X.164923  PMID:26486061
We conducted a community-based cross-sectional study to evaluate the role of genetics in determining the individual difference in total testosterone and sex hormone-binding globulin levels. Study participants comprised 730 Korean men consisting of 142 pairs of monozygotic twins, 191 pairs of siblings, and 259 father-offspring pairs from 270 families who participated in the Healthy Twin study. Serum concentration of total testosterone and sex hormone-binding globulin were measured by chemiluminescence immunoassay, and free testosterone and bioavailable testosterone were calculated using Vermeulen's method. Quantitative genetic analysis based on a variance decomposition model showed that the heritability of total testosterone, free testosterone, bioavailable testosterone, and sex hormone-binding globulin were 0.56, 0.45, 0.44, and 0.69, respectively after accounting for age and body mass index. Proportions of variance explained by age and body mass index varied across different traits, from 8% for total testosterone to 31% for sex hormone-binding globulin. Bivariate analysis showed a high degree of additive genetic correlation (ρG = 0.67) and a moderate degree of individual-specific environmental correlation (ρE = 0.42) between total testosterone and sex hormone-binding globulin. The findings confirmed the important role of genetics in determining the individually different levels of testosterone and sex hormone-binding globulin during adulthood in Korean men as found in non-Asian populations, which may suggest that common biologic control for determining testosterone level directly or indirectly through binding protein are largely shared among different populations.
  4,144 518 10
INVITED REVIEW
Molecular signaling involving intrinsically disordered proteins in prostate cancer
Anna Russo, Sara La Manna, Ettore Novellino, Anna Maria Malfitano, Daniela Marasco
September-October 2016, 18(5):673-681
DOI:10.4103/1008-682X.181817  PMID:27212129
Investigations on cellular protein interaction networks (PINs) reveal that proteins that constitute hubs in a PIN are notably enriched in Intrinsically Disordered Proteins (IDPs) compared to proteins that constitute edges, highlighting the role of IDPs in signaling pathways. Most IDPs rapidly undergo disorder-to-order transitions upon binding to their biological targets to perform their function. Conformational dynamics enables IDPs to be versatile and to interact with a broad range of interactors under normal physiological conditions where their expression is tightly modulated. IDPs are involved in many cellular processes such as cellular signaling, transcriptional regulation, and splicing; thus, their high-specificity/low-affinity interactions play crucial roles in many human diseases including cancer. Prostate cancer (PCa) is one of the leading causes of cancer-related mortality in men worldwide. Therefore, identifying molecular mechanisms of the oncogenic signaling pathways that are involved in prostate carcinogenesis is crucial. In this review, we focus on the aspects of cellular pathways leading to PCa in which IDPs exert a primary role.
  4,035 553 6
ORIGINAL ARTICLES
The prognostic value of lymphovascular invasion in radical prostatectomy: a systematic review and meta-analysis
Yi Huang, Hai Huang, Xiu-Wu Pan, Dan-Feng Xu, Xin-Gang Cui, Jie Chen, Yi Hong, Yi Gao, Lei Yin, Jian-Qing Ye, Lin Li
September-October 2016, 18(5):780-785
DOI:10.4103/1008-682X.156636  PMID:26459779
To systematically evaluate the prognostic value of lymphovascular invasion (LVI) in radical prostatectomy (RP) by a meta-analysis based on the published literature. To identify relevant studies, PubMed, Cochrane Library, and Web of Science database were searched from 1966 to May 2014. Finally, 25 studies (9503 patients) were included. LVI was found in 12.2% (1156/9503) of the RP specimens. LVI was found to be correlated with higher pathological tumor stages (greater than pT3 stage) (risk ratio [RR] 1.90, 95% confidence interval [CI] 1.73-2.08, P< 0.00001), higher Gleason scores (greater than GS = 7) (RR 1.30, 95% CI 1.23-1.38, P< 0.00001), positive pathological node (pN) status (RR 5.67, 95% CI 3.14-10.24, P< 0.00001), extracapsular extension (RR 1.72, 95% CI 1.46-2.02, P< 0.00001), and seminal vesicle involvement (RR 3.36, 95% CI 2.41-4.70, P< 0.00001). The pooled hazard ratio (HR) was statistically significant for Biochemical Recurrence-Free (BCR-free) probability (HR 2.05, 95% CI 1.64-2.56; Z = 6.30, P< 0.00001). Sensitivity analysis showed that the pooled HR and 95% CI were not significantly altered by the omission of any single study. Begg's Funnel plots showed no significant publication bias (P = 0.112). In conclusion, LVI exhibited a detrimental effect on the BCR-Free probability and clinicopathological features in RP specimens, and may prove to be an independent prognostic factor of BCR.
  4,110 466 12
An analysis of treatment preferences and sexual quality of life outcomes in female partners of Chinese men with erectile dysfunction
Hong-Jun Li, Wen-Jun Bai, Yu-Tian Dai, Wen-Ping Xu, Chia-Ning Wang, Han-Zhong Li
September-October 2016, 18(5):773-779
DOI:10.4103/1008-682X.159719  PMID:26459780
The impact of erectile dysfunction is distressing to both males and their female partners, but less attention has been paid to identify female partners' preferred treatment and sexual quality of life outcomes. The present analysis explores female partners' treatment preference for erectile dysfunction in Chinese Men. This was a phase 4, randomized, open-label, multicenter, crossover study in Chinese men with erectile dysfunction who were naïve to phosphodiesterase type 5 inhibitor treatments. Eligible patients were randomized to sequential 20-mg tadalafil/100-mg sildenafil or 100-mg sildenafil/20-mg tadalafil for 8 weeks each. Of 418 patients, female partners of 64 patients agreed to enter the study; of 64 patients who entered the study with female partners, 63 were randomized, and 62 completed the study. Baseline demographics and disease characteristics were comparable between treatment groups. Significantly more couples preferred tadalafil compared with sildenafil overall (75.4% vs 24.6%; P < 0.001), and irrespective of erectile dysfunction severity at baseline (P ≤ 0.005). Significant improvements in sexual quality of life scores were reported at endpoint (Visit 8) in male patients and female partners in both tadalafil and sildenafil treatment groups (P < 0.001). Significantly higher mean changes from baseline were observed for male patients in the tadalafil group compared with the sildenafil group for the erectile function (P = 0.013) and overall satisfaction (P = 0.019) International Index for Erectile Function domains and the spontaneity domain (P < 0.001) of the Psychological and Interpersonal Relationship Scale. No major safety concerns were reported during the study. Though both treatments were effective, safe, and tolerable, more couples preferred tadalafil compared with sildenafil.
  3,969 492 8
The calcium-sensing receptor participates in testicular damage in streptozotocin-induced diabetic rats
Wei-Yuan Kong, Li-Quan Tong, Hai-Jun Zhang, Yong-Gang Cao, Gong-Chen Wang, Jin-Zhi Zhu, Feng Zhang, Xue-Ying Sun, Tie-Hui Zhang, Lin-Lin Zhang
September-October 2016, 18(5):803-808
DOI:10.4103/1008-682X.160885  PMID:26387585
Male infertility caused by testicular damage is one of the complications of diabetes mellitus. The calcium-sensing receptor (CaSR) is expressed in testicular tissues and plays a pivotal role in calcium homeostasis by activating cellular signaling pathways, but its role in testicular damage induced by diabetes remains unclear. A diabetic model was established by a single intraperitoneal injection of streptozotocin (STZ, 40 mg kg−1 ) in Wistar rats. Animals then received GdCl 3 (an agonist of CaSR, 8.67 mg kg−1 ), NPS-2390 (an antagonist of CaSR, 0.20 g kg−1 ), or a combination of both 2 months after STZ injection. Diabetic rats had significantly lower testes weights and serum levels of testosterone compared to healthy rats, indicating testicular damage and dysfunction in STZ-induced diabetic rats. Compared with healthy controls, the testicular tissues of diabetic rats overexpressed the CaSR protein and had higher levels of malondialdehyde (MDA), lower superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity, and higher numbers of apoptotic germ cells. The testicular tissues from diabetic rats also expressed lower levels of Bcl-2 and higher levels of Bax and cleaved caspase-3 in addition to higher phosphorylation rates of c-Jun NH 2 -terminal protein kinase (JNK), p38, and extracellular signaling-regulated kinase (ERK) 1/2. The above parameters could be further increased or aggravated by the administration of GdCl 3 , but could be attenuated by injection of NPS-2390. In conclusion, the present results indicate that CaSR activation participates in diabetes-induced testicular damage, implying CaSR may be a potential target for protective strategies against diabetes-induced testicular damage and could help to prevent infertility in diabetic men.
  3,924 478 9
Microsurgical vasoepididymostomy for patients with infectious obstructive azoospermia: cause, outcome, and associated factors
Xiang-Feng Chen, Bin Chen, Wei Liu, Yan-Ping Huang, Hong-Xiang Wang, Yi-Ran Huang, Ping Ping
September-October 2016, 18(5):759-762
DOI:10.4103/1008-682X.175095  PMID:26924282
Azoospermia is of great importance to male infertility. Obstructive azoospermia (OA) due to infection is the most prevalent form of OA in China and has been less studied. We aim to observe the treatment outcome of microsurgical vasoepididymostomy (VE) and also to identify the factors relative to the result after reconstructive surgery. Two hundred and eight men presenting with OA due to infection during the study period from July 2010 to July 2013 were prospectively evaluated. Clinical examination, semen analysis, serum follicle stimulating hormone (FSH), and scrotal ultrasound were done before surgical exploration. Among the 198 men who were selected for surgical procedures, 159 candidates underwent microsurgical VE with sperm detected in the epididymal fluid. As for the other 39 cases, reconstruction was not feasible. The average age was 28.5 ± 3.9 years (range 22-38), with average follow-up being 16.5 ± 5.9 months (range 4-28). According to the 150 cases being followed after VE procedures, the total patency rate was 72% (108/150). During follow-up, 38.7% (58/150) natural pregnancies occurred, with overall live birth rate being 32.7% (49/150). Our data suggested that microsurgical VE is an effective therapy for postinfectious epididymal OA. Individualized counseling with prognosis based on etiology should be offered to patients to select optical therapy.
  3,890 494 6
Suppression of spermatogenesis by testosterone undecanoate-loaded injectable in situ-forming implants in adult male rats
Xiao-Wei Zhang, Chong Zhang, Wei Zhang, Dan Yang, Shu Meng, Ping Wang, Jing Guo, Dan-Hua Liu
September-October 2016, 18(5):791-797
DOI:10.4103/1008-682X.160886  PMID:26459781
We have investigated the feasibility of administration of testosterone undecanoate (TU)-loaded injectable in situ-forming implant (ISFI) for contraception in adult male Sprague-Dawley rats. Male rats were treated with vehicle, TU-loaded ISFIs (540, 270 and 135 mg TU kg−1 ) or TU injections (45 mg TU kg−1 every 30 days) for 120 days. Fertility tests served for determining infertility or restoration of fertility in treated rats. Serum testosterone concentration, epididymal sperm count, motility, morphology, and histology of the testis were monitored. The TU-loaded ISFIs increased serum testosterone levels in rats steadily without fluctuation over 3 months. One month after TU administration, the epididymal sperm count decreased significantly in all experimental groups. After 3 months, the animals treated with 270 and 135 mg kg−1 TU-loaded ISFIs were 100% infertile, and no implantation sites were produced in the mated females. However, some of males treated with 540 mg kg−1 ISFI or TU injections were still fertile but numbers of implantation sites were also significantly lower than control values. TU-loaded ISFI at an appropriate dose has potential as a long-acting male contraceptive drug that suppresses spermatogenesis consistently over a period of 3 months.
  3,963 384 2
Acquired premature ejaculation and male accessory gland infection: relevance of ultrasound examination
Sandro La Vignera, Rosita A Condorelli, Enzo Vicari, Vincenzo Favilla, Giuseppe Morgia, Aldo E Calogero
September-October 2016, 18(5):769-772
DOI:10.4103/1008-682X.155539  PMID:26387584
We have previously demonstrated a high frequency of premature ejaculation (PE) among patients with male accessory gland infection (MAGI). The aim of this study was to evaluate the ultrasound (US) features of patients with MAGI and acquired premature ejaculation (APE) associated (MAGI-APEpos). US evaluation of 50 MAGI-APEpos patients compared to 50 patients with MAGI without PE (MAGI-PEneg) which represent the control group. The diagnosis of APE was made through the evaluation of Intravaginal ejaculation latency time (IELT) and confirmed with the questionnaire PEDT (Premature Ejaculation Diagnostic Tool). The main outcome measure was represented by the frequency of US criteria suggestive of P (prostatitis), V (vesiculitis), and E (epididymitis) in MAGI-APEpos and MAGI-PEneg patients. MAGI-APEpos patients showed a total number of US criteria significantly higher compared to MAGI-PEneg patients. MAGI-APEpos showed a higher frequency of US criteria of V and E (complicated forms of MAGI). Finally, in MAGI-APEpos group, it was found a positive relationship between the anteroposterior diameter (APD) of the caudal tract of the epididymis and the APD of the seminal vesicles, as well as between both diameters and the PEDT score. MAGI-APEpos patients have a peculiar US characterization compared to MAGI-PEneg patients. According to these results, US evaluation of the epididymal and of the prostato vesicular tract should be considered in the practical clinical approach of patients with MAGI and APE. In particular, it could be a support for a possible pathophysiological interpretation of this clinical problem in these patients.
  3,799 504 8
Demethylation treatment restores erectile function in a rat model of hyperhomocysteinemia
Zheng Zhang, Lei-Lei Zhu, He-Song Jiang, Hai Chen, Yun Chen, Yu-Tian Dai
September-October 2016, 18(5):763-768
DOI:10.4103/1008-682X.163271  PMID:26585696
Methylation modification is an important cellular mechanism of gene expression regulation. Dimethylarginine dimethylaminohydrolase-2 (DDAH-2) protein is a pivotal molecular for endothelium function. To explore the effects of 5-aza-deoxycytidine (5-aza), a demethylation agent, in hyperhomocysteinemia (hhcy)-related erectile dysfunction (ED) rats, 5-aza (1 mg kg−1 ) was administrated to Sprague-Dawley hhcy-rats induced by supplemented methionine chow diet. Erectile function, nitric oxide-cyclic guanosine monophosphate (NO-cGMP) levels, expression of DDAH-2 protein and promoter methylation status of DDAH-2 were studied in the corpora cavernosa. We found that supplemented methionine diet induced a high homocysteine level after 6 weeks of treatment. DDAH-2 protein was down-regulated in the corpora cavernosa while the administration of 5-aza up-regulated DDAH-2 expression and restored erectile function. The methionine-fed rats showed high methylation levels of DDAH-2 promoter region while the group treated with 5-aza demonstrated lower-methylation levels when compared to the methionine-fed group. Besides, the administration of 5-aza improved NO and cGMP levels in methionine-fed rats. Therefore, the methylation mechanism involves in ED pathogenesis, and demethylation offers a potential new strategy for ED treatment.
  3,805 427 6
INVITED EDITORIAL
Intrinsically disordered proteins and prostate cancer: pouring new wine in an old bottle
Prakash Kulkarni
September-October 2016, 18(5):659-661
DOI:10.4103/1008-682X.184272  PMID:27427556
  3,535 664 4
INVITED RESEARCH HIGHLIGHT
Plasma miRNA expression profile in the diagnosis of late-onset hypogonadism
Nicholas Russell, Mathis Grossmann
September-October 2016, 18(5):713-715
DOI:10.4103/1008-682X.182819  PMID:27364544
  3,174 379 3
RESEARCH HIGHLIGHT
Cancer/testis antigens and obligate participation in multiple hallmarks of cancer: an update
Steven M Mooney, Krithika Rajagopalan, Govindan Rangarajan, Prakash Kulkarni
September-October 2016, 18(5):711-712
DOI:10.4103/1008-682X.174858  PMID:26908068
  3,088 407 4
LETTERS TO THE EDITOR
Commentary on "morphological characteristics and initial genetic study of multiple morphological anomalies of the flagella in China"
Charles Coutton, Christophe Arnoult, Pierre F Ray
September-October 2016, 18(5):812-812
DOI:10.4103/1008-682X.164195  PMID:26585697
  2,743 336 6
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