BioMed Research International: Urology http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Fibrinogen Alpha Chain Precursor and Apolipoprotein A-I in Urine as Biomarkers for Noninvasive Diagnosis of Calcium Oxalate Nephrolithiasis: A Proteomics Study Wed, 23 Jul 2014 10:45:14 +0000 http://www.hindawi.com/journals/bmri/2014/415651/ Calcium oxalate nephrolithiasis is the most common urological disease, but noninvasive and convenient methods of diagnosis are rarely available. Objective. The present study aimed to identify potential urine biomarkers for noninvasive diagnosis of CaOx nephrolithiasis. Methodology. Urine samples from 72 patients with CaOx nephrolithiasis and 30 healthy controls were collected and proteomics analysis was performed using matrix-assisted laser desorption/ionization-time of flight-mass spectrometer (MALDI-TOF-MS). Results. Thirteen proteins/peptides displayed statistically significant differences. The peptides of m/z 1207.23 and 2773.86 were selected by the genetic algorithm (GA) to build a possible diagnostic model. The area under the curve of m/z 1207.23 and 2773.86 was 0.936 and 0.987, respectively. The diagnostic model in distinguishing patients and healthy subjects showed 100% sensitivity and specificity. The peak at m/z 2773.86 was identified as fibrinogen alpha chain (FGA) with the sequence G.EGDFLAEGGGVR.G, and the peak at m/z 2773.86 was identified as apolipoprotein A-I (apoA-I) with the sequence L.PVLESFKVSFLSALEEYTKKLNTQ. Conclusion. The study results strongly suggested that urinary FGA and apoA-I are highly sensitive and specific biomarkers for noninvasive diagnosis of CaOx nephrolithiasis. Wei Zhu, Min Liu, Guang-Chun Wang, Bo Peng, Yang Yan, Jian-Ping Che, Qing-Wei Ma, Xu-Dong Yao, and Jun-Hua Zheng Copyright © 2014 Wei Zhu et al. All rights reserved. Functional MRI in Prostate Cancer Detection Wed, 23 Jul 2014 10:41:11 +0000 http://www.hindawi.com/journals/bmri/2014/590638/ Multiparametric magnetic resonance imaging (MP-MRI) has emerged as a promising method for the detection of prostate cancer. The functional MRI components of the MP-MRI consist of the diffusion weighted MRI, dynamic contrast enhanced MRI, and magnetic resonance spectroscopic imaging. The purpose of this paper is to review the existing literature about the use of functional MRI in prostate cancer detection. Sandeep Sankineni, Murat Osman, and Peter L. Choyke Copyright © 2014 Sandeep Sankineni et al. All rights reserved. Treatment of Bilateral Varicocele and Other Scrotal Comorbidities Using a Single Scrotal Access: Our Experience on 34 Patients Wed, 23 Jul 2014 00:00:00 +0000 http://www.hindawi.com/journals/bmri/2014/403603/ Introduction. Varicocele is the main cause of infertility in male and the most correctable cause of it too. In this study, we present our experience on 34 patients affected by bilateral varicocele and other scrotal comorbidities treated underwent surgery with a scrotal access. Materials and Methods. 34 patients were enrolled with clinical palpable and infraclinical (ultrasonic doppler scanning) bilateral varicocele and other comorbidities like right hydrocele, left hydrocele, bilateral hydrocele, and epididymal cyst. They all underwent scrotal bilateral varicocelectomy under local anesthesia. Results and Discussion. At 6 months, no other complications were reported. No case of testicular atrophy was observed. None had recurrence of varicocele. All scrotal comorbidities were treated as well. Conclusion. Scrotal access with local anesthesia is a safe and useful technique to treat patients with bilateral varicocele and other scrotal comorbidities. F. Iacono, A. Ruffo, D. Prezioso, G. Romeo, E. Illiano, G. Di Lauro, L. Romis, and S. Sansalone Copyright © 2014 F. Iacono et al. All rights reserved. Alga Ecklonia bicyclis, Tribulus terrestris, and Glucosamine Oligosaccharide Improve Erectile Function, Sexual Quality of Life, and Ejaculation Function in Patients with Moderate Mild-Moderate Erectile Dysfunction: A Prospective, Randomized, Placebo-Controlled, Single-Blinded Study Sun, 20 Jul 2014 07:21:46 +0000 http://www.hindawi.com/journals/bmri/2014/121396/ We aimed to evaluate the efficacy of oral therapy with alga Ecklonia bicyclis, Tribulus terrestris, and glucosamine oligosaccharide (Tradamix TX1000) in patients with erectile dysfunction (ED) at 3 months of follow-up. From January 2013 to September 2013, 177 patients diagnosed with mild-moderate ED (IIEF-EF < 26) were enrolled in this multicenter, single-blinded, placebo-controlled study and randomized in Group A (Tradamix, ) and Group B (placebo, ). Penile color Doppler ultrasound measures, IIEF-15 questionnaire, male sexual health questionnaire-ejaculation disorder (MSHQ-EjD), and sexual quality of life (SQoL-M) were collected. We observed significant changes of the IIEF-15 in Group A (mean difference: 11.54; ) at 3 months versus Group B (). PSV (), IIEF-intercourse satisfaction (), IIEF-orgasmic function (mean ), IIEF-sexual desire (), IIEF-overall satisfaction (), MSHQ-EjD (mean difference: 1.21; ), and SQoL-M (mean difference: 10.2; ) were significantly changed in Group A versus baseline and Group B. Patients with moderate arterial dysfunction showed significant increase of PSV (), IIEF-EF (), MSHQ-EjD (), and SQoL-M () in Group A. Therapy with Tradamix improves erectile and ejaculation function and sexual quality of life in patients with mild-moderate ED and in particular for those with moderate arterial dysfunction. Salvatore Sansalone, Rosario Leonardi, Gabriele Antonini, Antonio Vitarelli, Giuseppe Vespasiani, Dragoslav Basic, Giuseppe Morgia, Sebastiano Cimino, and Giorgio Ivan Russo Copyright © 2014 Salvatore Sansalone et al. All rights reserved. Acute In Vivo Response to an Alternative Implant for Urogynecology Thu, 17 Jul 2014 14:54:32 +0000 http://www.hindawi.com/journals/bmri/2014/853610/ Purpose. To investigate in vivo the acute host response to an alternative implant designed for the treatment of stress urinary incontinence (SUI) and pelvic organ prolapse (POP). Methods. A biodegradable scaffold was produced from poly-L-lactic acid (PLA) using the electrospinning technique. Human and rat adipose-derived stem cells (ADSCs) were isolated and characterized by fluorescence-activated cell sorting and differentiation assays. PLA scaffolds were seeded and cultured for 2 weeks with human or rat ADSCs. Scaffolds with and without human or rat ADSCs were implanted subcutaneously on the abdominal wall of rats. After 3 and 7 days, 6 animals from each group were sacrificed. Sections from each sample were analyzed by Haematoxylin and Eosin staining, Sirius red staining, and immunohistochemistry for CD68, PECAM-1, and collagen I and III. Results. Animals responded to the scaffolds with an acute macrophage response. After 7 days of implantation, there was extensive host cell penetration, new blood vessel formation, and new collagen deposition throughout the full thickness of the samples without obvious differences between cell-containing and cell-free scaffolds. Conclusions. The acute in vivo response to an alternative implant (both with and without cells) for the treatment of SUI and POP showed good acute integration into the host tissues. Sabiniano Roman Regueros, Maarten Albersen, Stefano Manodoro, Silvia Zia, Nadir I. Osman, Anthony J. Bullock, Christopher R. Chapple, Jan Deprest, and Sheila MacNeil Copyright © 2014 Sabiniano Roman Regueros et al. All rights reserved. Multiparametric MRI in Biopsy Guidance for Prostate Cancer: Fusion-Guided Sun, 13 Jul 2014 07:06:32 +0000 http://www.hindawi.com/journals/bmri/2014/439171/ Prostate cancer (PCa) is the most common solid-organ malignancy among American men and the second most deadly. Current guidelines recommend a 12-core systematic biopsy following the finding of an elevated serum prostate-specific antigen (PSA). However, this strategy fails to detect an unacceptably high percentage of clinically significant cancers, leading researchers to develop new, innovative methods to improve the effectiveness of prostate biopsies. Multiparametric-MRI (MP-MRI) has emerged as a promising instrument in identifying suspicious regions within the prostate that require special attention on subsequent biopsy. Fusion platforms, which incorporate the MP-MRI into the biopsy itself and provide active targets within real-time imaging, have shown encouraging results in improving the detection rate of significant cancer. Broader applications of this technology, including MRI-guided focal therapy for prostate cancer, are in early phase trials. Jason T. Rothwax, Arvin K. George, Bradford J. Wood, and Peter A. Pinto Copyright © 2014 Jason T. Rothwax et al. All rights reserved. Stem Cell Based Gene Therapy in Prostate Cancer Thu, 10 Jul 2014 11:25:18 +0000 http://www.hindawi.com/journals/bmri/2014/549136/ Current prostate cancer treatment, especially hormone refractory cancer, may create profound iatrogenic outcomes because of the adverse effects of cytotoxic agents. Suicide gene therapy has been investigated for the substitute modality for current chemotherapy because it enables the treatment targeting the cancer cells. However the classic suicide gene therapy has several profound side effects, including immune-compromised due to viral vector. Recently, stem cells have been regarded as a new upgraded cellular vehicle or vector because of its homing effects. Suicide gene therapy using genetically engineered mesenchymal stem cells or neural stem cells has the advantage of being safe, because prodrug administration not only eliminates tumor cells but consequently kills the more resistant therapeutic stem cells as well. The attractiveness of prodrug cancer gene therapy by stem cells targeted to tumors lies in activating the prodrug directly within the tumor mass, thus avoiding systemic toxicity. Therapeutic achievements using stem cells in prostate cancer include the cytosine deaminase/5-fluorocytosine prodrug system, herpes simplex virus thymidine kinase/ganciclovir, carboxyl esterase/CPT11, and interferon-beta. The aim of this study is to review the stem cell therapy in prostate cancer including its proven mechanisms and also limitations. Jae Heon Kim, Hong Jun Lee, and Yun Seob Song Copyright © 2014 Jae Heon Kim et al. All rights reserved. Immunocontraceptives: New Approaches to Fertility Control Thu, 10 Jul 2014 06:27:29 +0000 http://www.hindawi.com/journals/bmri/2014/868196/ The rapidly increasing global population has bowed the attention of family planning and associated reproductive health programmes in the direction of providing a safe and reliable method which can be used to limit family size. The world population is estimated to exceed a phenomenal 10 billion by the year 2050 A.D., thus presenting a real jeopardy of overpopulation with severe implications for the future. Despite the availability of contraceptive methods, there are over one million elective abortions globally each year due to unintended pregnancies, having devastating impact on reproductive health of women worldwide. This highlights the need for the development of newer and improved contraceptive methods. A novel contraceptive approach that is gaining substantial attention is “immunocontraception” targeting gamete production, gamete outcome, or gamete function. Amongst these, use of sperm antigens (gamete function) seems to be an exciting and feasible approach. However, the variability of immune response and time lag to attain titer among vaccinated individuals after active immunization has highlighted the potential relevance of preformed antibodies in this league. This review is an attempt to analyze the current status and progress of immunocontraceptive approaches with respect to their establishment as a future fertility control agent. Kiranjeet Kaur and Vijay Prabha Copyright © 2014 Kiranjeet Kaur and Vijay Prabha. All rights reserved. A Comparative Performance Analysis of Total PSA, Percentage Free PSA, PSA Velocity, and PSA Density versus the Detection of Primary Circulating Prostate Cells in Predicting Initial Prostate Biopsy Findings in Chilean Men Tue, 01 Jul 2014 00:00:00 +0000 http://www.hindawi.com/journals/bmri/2014/676572/ Introduction. PSA parameters have been used in an attempt to improve the diagnostic yield of prostate screening tests; the detection of primary malignant circulating prostate cells (CPCs) may improve the diagnostic yield of screening and therefore avoid unnecessary biopsies. Patients and Methods. Prospective study of all men undergoing initial prostate biopsy due to an elevated total serum PSA. Free percent PSA, PSA velocity, and PSA density were determined. Primary CPCs were detected using standard immunocytochemistry. A positive test for CPCs was defined as one cell PSA (+) P504S (+) in an 8 ml blood sample. Positive predictive and negative predictive values, specificity, and sensitivity were calculated for each test as well as the number of biopsies avoided and cancers missed. Results. 303 men participated in the study of whom 113/303 (37.3%) men had prostate cancer. Of the three PSA based parameters, free percent PSA was superior, sensitivity 70.8%, and specificity 67.4%. Primary CPCs detection had a sensitivity of 88.5% and a specificity of 88.4% avoiding 181 (59.7%) biopsies, detecting 93/95 (98%) of clinically significant cancers, and missing 13 (11.5%) low grade, small volume tumors. Conclusions. The use of primary CPCs as a sequential test could decrease the number of initial prostate biopsies missing those cancers which are treated by active observation. Nigel P. Murray, Eduardo Reyes, Nelson Orellana, Cynthia Fuentealba, and Ricardo Dueñas Copyright © 2014 Nigel P. Murray et al. All rights reserved. Enhanced Efficacy of Bleomycin in Bladder Cancer Cells by Photochemical Internalization Mon, 30 Jun 2014 06:56:31 +0000 http://www.hindawi.com/journals/bmri/2014/921296/ Bleomycin is a cytotoxic chemotherapeutic agent widely used in cancer treatment. However, its efficacy in different cancers is low, possibly due to limited cellular internalization. In this study, a novel approach known as photochemical internalization (PCI) was explored to enhance bleomycin delivery in bladder cancer cells (human T24 and rat AY-27), as bladder cancer is a potential indication for use of PCI with bleomycin. The PCI technique was mediated by the amphiphilic photosensitizer disulfonated tetraphenyl chlorin (TPCS2a) and blue light (435 nm). Two additional strategies were explored to further enhance the cytotoxicity of bleomycin; a novel peptide drug ATX-101 which is known to impair DNA damage responses, and the protease inhibitor E-64 which may reduce bleomycin degradation by inhibition of bleomycin hydrolase. Our results demonstrate that the PCI technique enhances the bleomycin effect under appropriate conditions, and importantly we show that PCI-bleomycin treatment leads to increased levels of DNA damage supporting that the observed effect is due to increased bleomycin uptake. Impairing the DNA damage responses by ATX-101 further enhances the efficacy of the PCI-bleomycin treatment, while inhibiting the bleomycin hydrolase does not. Yan Baglo, Lars Hagen, Anders Høgset, Finn Drabløs, Marit Otterlei, and Odrun A. Gederaas Copyright © 2014 Yan Baglo et al. All rights reserved. Role of the Adjacent Stroma Cells in Prostate Cancer Development and Progression: Synergy between TGF-β and IGF Signaling Wed, 25 Jun 2014 11:06:39 +0000 http://www.hindawi.com/journals/bmri/2014/502093/ This review postulates the role of transforming growth factor-beta (TGF-β) and insulin-like growth factor (IGF-I/IGF-II) signaling in stromal cells during prostate carcinogenesis and progression. It is known that stromal cells have a reciprocal relationship to the adjacent epithelial cells in the maintenance of structural and functional integrity of the prostate. An interaction between TGF-β and IGF signaling occupies a central part in this stromal-epithelial interaction. An increase in TGF-β and IGF signaling will set off the imbalance of this relationship and will lead to cancer development. A continuous input from TGF-β and IGF in the tumor microenvironment will result in cancer progression. Understanding of these events can help prevention, diagnosis, and therapy of prostate cancer. Chung Lee, Zhenyu Jia, Farah Rahmatpanah, Qiang Zhang, Xiaolin Zi, Michael McClelland, and Dan Mercola Copyright © 2014 Chung Lee et al. All rights reserved. Clinical Significance of Serum Soluble T Cell Regulatory Molecules in Clear Cell Renal Cell Carcinoma Wed, 25 Jun 2014 10:55:04 +0000 http://www.hindawi.com/journals/bmri/2014/396064/ To clarify the role of serum soluble T cell regulatory molecules in clear cell renal cell carcinoma (CCRCC), we measured the serum levels of soluble interleukin-2 receptor (sIL-2R), soluble B7-H3 (sB7-H3), and soluble cytotoxic T lymphocyte associated antigen-4 (sCTLA-4) in 70 CCRCC patients and 35 healthy controls. We investigated correlations between the serum levels of these soluble T cell regulatory molecules and the pathological grade, clinical stage, and prognosis of CCRCC. We also assessed the relations among each of these soluble molecules. As a result, the serum level of sIL-2R was significantly higher in CCRCC patients than in healthy controls (). In addition, elevation of serum sIL-2R was significantly correlated with the clinical stage (), and the survival of patients with high sIL-2R levels was shorter than that of patients with low sIL-2R levels (). Furthermore, the serum level of sB7-H3 was also significantly correlated with the clinical stage (), while the sIL-2R and sB7-H3 levels showed a positive correlation with each other (, ). These results indicate that the serum level of sIL-2R reflects tumor progression in CCRCC patients. In addition, the possibility was suggested that the IL-2/IL-2R and B7-H3 pathways may be involved in the progression of CCRCC. Akinori Masuda, Kyoko Arai, Daisaku Nishihara, Tomoya Mizuno, Hideo Yuki, Tsunehito Kambara, Hironori Betsunoh, Hideyuki Abe, Masahiro Yashi, Yoshitatsu Fukabori, Ken-Ichiro Yoshida, and Takao Kamai Copyright © 2014 Akinori Masuda et al. All rights reserved. Extremely Low Frequency Magnetic Fields Induce Spermatogenic Germ Cell Apoptosis: Possible Mechanism Sun, 15 Jun 2014 08:15:48 +0000 http://www.hindawi.com/journals/bmri/2014/567183/ The energy generated by an extremely low frequency electromagnetic field (ELF-EMF) is too weak to directly induce genotoxicity. However, it is reported that an extremely low frequency magnetic field (ELF-MF) is related to DNA strand breakage and apoptosis. The testes that conduct spermatogenesis through a dynamic cellular process involving meiosis and mitosis seem vulnerable to external stress such as heat, MF exposure, and chemical or physical agents. Nevertheless the results regarding adverse effects of ELF-EMF on human or animal reproductive functions are inconclusive. According to the guideline of the International Commission on Non-Ionizing Radiation Protection (ICNIRP; 2010) for limiting exposure to time-varying MF (1 Hz to 100 kHz), overall conclusion of epidemiologic studies has not consistently shown an association between human adverse reproductive outcomes and maternal or paternal exposure to low frequency fields. In animal studies there is no compelling evidence of causal relationship between prenatal development and ELF-MF exposure. However there is increasing evidence that EL-EMF exposure is involved with germ cell apoptosis in testes. Biophysical mechanism by which ELF-MF induces germ cell apoptosis has not been established. This review proposes the possible mechanism of germ cell apoptosis in testes induced by ELF-MF. Sang-Kon Lee, Sungman Park, Yoon-Myoung Gimm, and Yoon-Won Kim Copyright © 2014 Sang-Kon Lee et al. All rights reserved. Standardization of Multiparametric Prostate MR Imaging Using PI-RADS Mon, 09 Jun 2014 11:44:07 +0000 http://www.hindawi.com/journals/bmri/2014/431680/ The purpose of this paper is to introduce and describe the Prostate Imaging and Reporting Archiving Data System (PI-RADS). For every single parameter the PI-RADS scoring system will be explained and magnetic resonance imaging (MRI) examples will be given. In the end two patient cases are presented to explain the overall interpretation score in multiparametric imaging. Joyce G. R. Bomers and Jelle O. Barentsz Copyright © 2014 Joyce G. R. Bomers and Jelle O. Barentsz. All rights reserved. Recent Advances in the Biology of the Urothelium and Applications for Urinary Bladder Dysfunction Mon, 09 Jun 2014 10:56:20 +0000 http://www.hindawi.com/journals/bmri/2014/341787/ Rok Romih, Michael Winder, and Gilho Lee Copyright © 2014 Rok Romih et al. All rights reserved. Inhibition of Nitric Oxide Synthase Prevents Muscarinic and Purinergic Functional Changes and Development of Cyclophosphamide-Induced Cystitis in the Rat Sun, 01 Jun 2014 12:35:15 +0000 http://www.hindawi.com/journals/bmri/2014/359179/ Nitric oxide (NO) has pivotal roles in cyclophosphamide- (CYP-) induced cystitis during which mucosal nitric oxide synthase (NOS) and muscarinic M5 receptor expressions are upregulated. In cystitis, urothelial muscarinic NO-linked effects hamper contractility. Therefore we wondered if a blockade of this axis also affects the induction of cystitis in the rat. Rats were pretreated with saline, the muscarinic receptor antagonist 4-DAMP (1 mg/kg ip), or the NOS inhibitor L-NAME (30 mg/kg ip) for five days. 60 h before the experiments the rats were treated with saline or CYP. Methacholine-, ATP-, and adenosine-evoked responses were smaller in preparations from CYP-treated rats than from saline-treated ones. Pretreatment with 4-DAMP did not change this relation, while pretreatment with L-NAME normalized the responses in the CYP-treated animals. The functional results were strengthened by the morphological observations; 4-DAMP pretreatment did not affect the parameters studied, namely, expression of muscarinic M5 receptors, P1A1 purinoceptors, mast cell distribution, or bladder wall enlargement. However, pretreatment with L-NAME attenuated the differences. Thus, the current study provides new insights into the complex mechanisms behind CYP-induced cystitis. The NO effects coupled to urothelial muscarinic receptors have a minor role in the development of cystitis. Inhibition of NOS may prevent the progression of cystitis. Patrik Aronsson, Renata Vesela, Martin Johnsson, Yasin Tayem, Vladimir Wsol, Michael Winder, and Gunnar Tobin Copyright © 2014 Patrik Aronsson et al. All rights reserved. Pathological Feature and Immunoprofile of Cystitis Glandularis Accompanied with Upper Urinary Tract Obstruction Thu, 29 May 2014 16:14:23 +0000 http://www.hindawi.com/journals/bmri/2014/872170/ Objective. To explore the pathological feature and immunoprofile of immunoprofile accompanied with upper urinary tract obstruction and the immunoprofile in various types of glandular cystitis. Methods. Pathological sections from 31 cases of cystitis glandularis with upper urinary tract obstruction and 34 cases of cystitis glandularis without upper urinary tract obstruction were observed as pathological feature on microscopy. Meanwhile, an immunohistochemical analysis was employed to determine the expression of p53, Ki67, p21, MMP-9, MUC1, MUC2, and COX-2. Results. In the two groups, main pathological type was transitional epithelial, followed by intestinal epithelial; other types were a few, and the difference between the two groups was not significant. All immunohistochemical expressions of p53, Ki67, p21, MMP-9, MUC1, MUC2, and COX-2 were positive in varying degrees, and there was no significant difference between the groups. Transitional epithelial type was compared with mixed type; the difference of COX-2 was significant, . The differences of immunohistochemical expression among other different pathologic types were not significant. Conclusions. It is suggested that glandular cystitis accompanied with upper urinary tract obstruction shares the same pathological feature and immunoprofile as that without upper urinary tract obstruction. No significant differences of immunohistochemical expression in tissue are in cystitis glandularis with different pathological types. Aihua Li, Jun Zhou, Honghai Lu, Xiaoming Zuo, Sikuan Liu, Feng Zhang, Weiwu Li, Wei Fang, and Binghui Zhang Copyright © 2014 Aihua Li et al. All rights reserved. Prostate Cancer and Bone: The Elective Affinities Wed, 28 May 2014 00:00:00 +0000 http://www.hindawi.com/journals/bmri/2014/167035/ The onset of metastases dramatically changes the prognosis of prostate cancer patients, determining increased morbidity and a drastic fall in survival expectancy. Bone is a common site of metastases in few types of cancer, and it represents the most frequent metastatic site in prostate cancer. Of note, the prevalence of tumor relapse to the bone appears to be increasing over the years, likely due to a longer overall survival of prostate cancer patients. Bone tropism represents an intriguing challenge for researchers also because the preference of prostate cancer cells for the bone is the result of a sequential series of targetable molecular events. Many factors have been associated with the peculiar ability of prostate cancer cells to migrate in bone marrow and to determine mixed osteoblastic/osteolytic lesions. As anticipated by the success of current targeted therapy aimed to block bone resorption, a better understanding of molecular affinity between prostate cancer and bone microenvironment will permit us to cure bone metastasis and to improve prognosis of prostate cancer patients. Nadia Rucci and Adriano Angelucci Copyright © 2014 Nadia Rucci and Adriano Angelucci. All rights reserved. ATP during Early Bladder Stretch Is Important for Urgency in Detrusor Overactivity Patients Tue, 27 May 2014 11:04:11 +0000 http://www.hindawi.com/journals/bmri/2014/204604/ ATP is an important mediator of urgency in women with detrusor overactivity (DO). In order to understand how different degrees of bladder stretch elicited ATP release in DO patients compared with controls, sequential aliquots were collected during cystometry and ATP release was measured at each degree of bladder filling, in female patients with DO and controls. In both DO and control groups, ATP release was induced during bladder filling, suggesting that stretch stimulated further ATP release. However, the luminal ATP concentrations were already high at early filling stage (200 mL), which was even greater than those at the later filling stages (400 mL and maximum cystometric capacity, MCC), indicating that a substantial ATP release has been induced during early filling (200 mL) in both DO and controls. In DO, ATP release at 200 mL was significantly higher in those with low first desire to void (FDV) (≤200 mL) than in those with higher FDV (>200 mL); this may suggest that ATP release at early stretch may play an important role in urgency (early sensation) in DO. ATP concentrations remained unchanged after voiding, suggesting that voiding did not further induce ATP release into intraluminal fluid. Y. Cheng, K. J. Mansfield, W. Allen, R. Chess-Williams, E. Burcher, and K. H. Moore Copyright © 2014 Y. Cheng et al. All rights reserved. Multiparametric MRI for Recurrent Prostate Cancer Post Radical Prostatectomy and Postradiation Therapy Sun, 25 May 2014 09:17:27 +0000 http://www.hindawi.com/journals/bmri/2014/316272/ The clinical suspicion of local recurrence of prostate cancer (PCa) after radical prostatectomy (RP) and after radiation therapy (RT) is based on the onset of biochemical failure. The aim of this paper was to review the current role of multiparametric-MRI (mp-MRI) in the detection of locoregional recurrence. A systematic literature search using the Medline and Cochrane Library databases was performed from January 1995 up to November 2013. Bibliographies of retrieved and review articles were also examined. Only those articles reporting complete data with clinical relevance for the present review were selected. This review article is divided into two major parts: the first one considers the role of mp-MRI in the detection of PCa local recurrence after RP; the second part provides an insight about the impact of mp-MRI in the depiction of locoregional recurrence after RT (interstitial or external beam). Published data indicate an emerging role for mp-MRI in the detection and localization of locally recurrent PCa both after RP and RT which represents an information of paramount importance to perform focal salvage treatments. Flavio Barchetti and Valeria Panebianco Copyright © 2014 Flavio Barchetti and Valeria Panebianco. All rights reserved. Exploring the miRNA-mRNA Regulatory Network in Clear Cell Renal Cell Carcinomas by Next-Generation Sequencing Expression Profiles Thu, 22 May 2014 16:11:29 +0000 http://www.hindawi.com/journals/bmri/2014/948408/ Altered microRNA (miRNA) expression is a hallmark of many cancer types. The combined analysis of miRNA and messenger RNA (mRNA) expression profiles is crucial to identifying links between deregulated miRNAs and oncogenic pathways. Therefore, we investigated the small non-coding (snc) transcriptomes of nine clear cell renal cell carcinomas (ccRCCs) and adjacent normal tissues for alterations in miRNA expression using a publicly available small RNA-Sequencing (sRNA-Seq) raw-dataset. We constructed a network of deregulated miRNAs and a set of differentially expressed genes publicly available from an independent study to in silico determine miRNAs that contribute to clear cell renal cell carcinogenesis. From a total of 1,672 sncRNAs, 61 were differentially expressed across all ccRCC tissue samples. Several with known implications in ccRCC development, like the upregulated miR-21-5p, miR-142-5p, as well as the downregulated miR-106a-5p, miR-135a-5p, or miR-206. Additionally, novel promising candidates like miR-3065, which i.a. targets NRP2 and FLT1, were detected in this study. Interaction network analysis revealed pivotal roles for miR-106a-5p, whose loss might contribute to the upregulation of 49 target mRNAs, miR-135a-5p (32 targets), miR-206 (28 targets), miR-363-3p (22 targets), and miR-216b (13 targets). Among these targets are the angiogenesis, metastasis, and motility promoting oncogenes c-MET, VEGFA, NRP2, and FLT1, the latter two coding for VEGFA receptors. Sören Müller and Katharina Nowak Copyright © 2014 Sören Müller and Katharina Nowak. All rights reserved. CD57 Expression in Incidental, Clinically Manifest, and Metastatic Carcinoma of the Prostate Thu, 22 May 2014 14:17:35 +0000 http://www.hindawi.com/journals/bmri/2014/356427/ Objectives. CD57 is normally found on NK-cells, but little is known about its expression in prostatic tissue. Methods. We investigated CD57 expression by immunohistochemistry using tissue microarrays containing 3262 prostate cancers (PCa), lymph node metastases, and benign prostatic tissue. The results were compared with clinical and pathological parameters. Results. Overall, 87% of PCa showed a moderate or strong expression of CD57. There was no significant difference to corresponding benign prostatic tissue. CD57 was increasingly lost from incidental over clinically manifest cancers to metastases. It correlated significantly with Gleason grade and pT-category, but not with PSA tissue expression. Loss of CD57 expression was an independent risk factor for PSA recurrence after prostatectomy in a multivariate Cox regression analysis. In standard sections, CD57 expression was heterogeneous, especially in large, high-grade PCa. Conclusions. There is a peculiar expression of CD57 in PCa and benign prostatic tissue. CD57 loss is associated with tumor dedifferentiation and tumor size. However, the use of this marker for prognostic purposes is hampered by its heterogeneous expression. Holger Wangerin, Glen Kristiansen, Thorsten Schlomm, Carsten Stephan, Sven Gunia, Annette Zimpfer, Wilko Weichert, Guido Sauter, and Andreas Erbersdobler Copyright © 2014 Holger Wangerin et al. All rights reserved. Sunitinib Combined with Angiotensin-2 Type-1 Receptor Antagonists Induces More Necrosis: A Murine Xenograft Model of Renal Cell Carcinoma Thu, 22 May 2014 11:50:57 +0000 http://www.hindawi.com/journals/bmri/2014/901371/ Background. Angiotensin-2 type-1 receptor antagonists not are only antihypertensive drugs but also can inhibit VEGF production. We hypothesised that adding telmisartan to sunitinib could potentiate the antiangiogenic effects. Material and Methods. 786-O cell lines were injected in nude mice. After tumor development, mice were divided into 4 groups: the first was the control group (DMSO), the second group was treated with sunitinib alone, the third group was treated with telmisartan alone, and the fourth group was treated with the combination. Drugs were orally administered every day for four weeks. Animals were sacrificed after treatment. Blood and tumor tissues were collected for analysis by immunohistochemistry, Western Blot, and ELISA methods. Results. All animals developed a ccRCC and ten in each group were treated. Using a kinetic model, tumors tended to grow slower in the combination group compared to others (). Compared to sunitinib alone, the addition of telmisartan significantly increased tissue necrosis (). Central microvascular density decreased () as well as circulating VEGF (). There was no significant variation in proliferation or apoptosis markers. Conclusion. The combination of sunitinib and telmisartan revealed an enhancement of the blockage of the VEGF pathway on renal tumor resulting in a decrease in neoangiogenesis and an increase in necrosis. Grégory Verhoest, Thibault Dolley-Hitze, Florence Jouan, Marc-Antoine Belaud-Rotureau, Emmanuel Oger, Audrey Lavenu, Karim Bensalah, Yannick Arlot-Bonnemains, Nicolas Collet, Nathalie Rioux-Leclercq, and Cécile Vigneau Copyright © 2014 Grégory Verhoest et al. All rights reserved. Epigenetic Alterations of Chromosome 3 Revealed by NotI-Microarrays in Clear Cell Renal Cell Carcinoma Thu, 22 May 2014 10:45:12 +0000 http://www.hindawi.com/journals/bmri/2014/735292/ This study aimed to clarify epigenetic and genetic alterations that occur during renal carcinogenesis. The original method includes chromosome 3 specific NotI-microarrays containing 180 NotI-clones associated with 188 genes for hybridization with 23 paired normal/tumor DNA samples of primary clear cell renal cell carcinomas (ccRCC). Twenty-two genes showed methylation and/or deletion in 17–57% of tumors. These genes include tumor suppressors or candidates (VHL, CTDSPL, LRRC3B, ALDH1L1, and EPHB1) and genes that were not previously considered as cancer-associated (e.g., LRRN1, GORASP1, FGD5, and PLCL2). Bisulfite sequencing analysis confirmed methylation as a frequent event in ccRCC. A set of six markers (NKIRAS1/RPL15, LRRN1, LRRC3B, CTDSPL, GORASP1/TTC21A, and VHL) was suggested for ccRCC detection in renal biopsies. The mRNA level decrease was shown for 6 NotI-associated genes in ccRCC using quantitative PCR: LRRN1, GORASP1, FOXP1, FGD5, PLCL2, and ALDH1L1. The majority of examined genes showed distinct expression profiles in ccRCC and papillary RCC. The strongest extent and frequency of downregulation were shown for ALDH1L1 gene both in ccRCC and papillary RCC. Moreover, the extent of ALDH1L1 mRNA level decrease was more pronounced in both histological types of RCC stage III compared with stages I and II (). The same was observed for FGD5 gene in ccRCC (). Alexey A. Dmitriev, Evgeniya E. Rudenko, Anna V. Kudryavtseva, George S. Krasnov, Vasily V. Gordiyuk, Nataliya V. Melnikova, Eduard O. Stakhovsky, Oleksii A. Kononenko, Larissa S. Pavlova, Tatiana T. Kondratieva, Boris Y. Alekseev, Eleonora A. Braga, Vera N. Senchenko, and Vladimir I. Kashuba Copyright © 2014 Alexey A. Dmitriev et al. All rights reserved. Multiple Determinations of Sperm DNA Fragmentation Show That Varicocelectomy Is Not Indicated for Infertile Patients with Subclinical Varicocele Tue, 20 May 2014 11:56:29 +0000 http://www.hindawi.com/journals/bmri/2014/181396/ Varicocele is one of the most common causes of low semen quality, which is reflected in high percentages of sperm cells with fragmented DNA. While varicocelectomy is usually performed to ameliorate a patient’s fertility, its impact on sperm DNA integrity in the case of subclinical varicocele is poorly documented. In this study, multiple DNA fragmentation analyses (TUNEL, SCD, and SCSA) were performed on semen samples from sixty infertile patients with varicocele (15 clinical varicoceles, 19 clinical varicoceles after surgical treatment, 16 subclinical varicoceles, and 10 subclinical varicoceles after surgical treatment). TUNEL, SCD, and SCSA assays all showed substantial sperm DNA fragmentation levels that were comparable between subclinical and clinical varicocele patients. Importantly, varicocelectomy did improve sperm quality in patients with clinical varicocele; however, this was not the case in patients with subclinical varicocele. In summary, although infertile patients with clinical and subclinical varicocele have similar sperm DNA quality, varicocelectomy should only be advised for patients with clinical varicocele. Agustín García-Peiró, Jordi Ribas-Maynou, María Oliver-Bonet, Joaquima Navarro, Miguel A. Checa, Alexandros Nikolaou, María J. Amengual, Carlos Abad, and Jordi Benet Copyright © 2014 Agustín García-Peiró et al. All rights reserved. The Role of Histone Ubiquitination during Spermatogenesis Mon, 19 May 2014 00:00:00 +0000 http://www.hindawi.com/journals/bmri/2014/870695/ Protein ubiquitin-proteasome (ubiquitin-proteasome) system is the major mechanism responsible for protein degradation in eukaryotic cell. During spermatogenesis, the replacement of histone by protamine is vital for normal sperm formation, which is involved in ubiquitination enzymes expressed in testis. Recently, histone ubiquitin ligases have been shown to play critical roles in several aspects of spermatogenesis, such as meiotic sex chromosome inactivation (MSCI), DNA damage response, and spermiogenesis. In this review, we highlight recent progress in the discovery of several histone ubiquitin ligases and elaborate mechanisms of how these enzymes are involved in these processes through knockout mouse model. Using Huwe1, UBR2, and RNF8 as examples, we emphasized the diverse functions for each enzyme and the broad involvement of these enzymes in every stage, from spermatogonia differentiation and meiotic division to spermiogenesis; thus histone ubiquitin ligases represent a class of enzymes, which play important roles in spermatogenesis through targeting histone for ubiquitination and therefore are involved in transcription regulation, epigenetic modification, and other processes essential for normal gametes formation. Kai Sheng, Xiaotong Liang, Sizhou Huang, and Wenming Xu Copyright © 2014 Kai Sheng et al. All rights reserved. Luminal DMSO: Effects on Detrusor and Urothelial/Lamina Propria Function Sun, 18 May 2014 12:12:08 +0000 http://www.hindawi.com/journals/bmri/2014/347616/ DMSO is used as a treatment for interstitial cystitis and this study examined the effects of luminal DMSO treatment on bladder function and histology. Porcine bladder was incubated without (controls) or with DMSO (50%) applied to the luminal surface and the release of ATP, acetylcholine, and LDH assessed during incubation and in tissues strips after DMSO incubation. Luminally applied DMSO caused ATP, Ach, and LDH release from the urothelial surface during treatment, with loss of urothelial layers also evident histologically. In strips of urothelium/lamina propria from DMSO pretreated bladders the release of both ATP and Ach was depressed, while contractile responses to carbachol were enhanced. Detrusor muscle contractile responses to carbachol were not affected by DMSO pretreatment, but neurogenic responses to electrical field stimulation were enhanced. The presence of an intact urothelium/lamina propria inhibited detrusor contraction to carbachol by 53% and this inhibition was significantly reduced in DMSO pretreated tissues. Detection of LDH in the treatment medium suggests that DMSO permeabilised urothelial membranes causing leakage of cytosolic contents including ATP and Ach rather than enhancing release of these mediators. The increase in contractile response and high levels of ATP are consistent with initial flare up in IC/PBS symptoms after DMSO treatment. Katrina J. Smith, Russ Chess-Williams, and Catherine McDermott Copyright © 2014 Katrina J. Smith et al. All rights reserved. Nonsteroidal Anti-Inflammatory Drugs and Prostatic Diseases Mon, 12 May 2014 06:48:12 +0000 http://www.hindawi.com/journals/bmri/2014/436123/ Prostatic diseases are characterized by increased activity of cytokines, growth factors, and cyclooxygenases- (COX-) 1 and 2. Activation of COX-1 and COX-2 results in increased levels of prostaglandins and the induction of angiogenic, antiapoptotic and inflammatory processes. Inhibition of COX enzymes by members of the widely used nonsteroidal anti-inflammatory drug (NSAID) class of drugs decreases prostaglandin production, and exerts a variety of anti-inflammatory, antipyretic, and antinociceptive effects. While numerous in vitro, in vivo, and clinical studies have shown that NSAIDs inhibit the risk and progression of prostatic diseases, the relationship between NSAIDs and such diseases remains controversial. Here we review the literature in this area, critically analyzing the benefits and caveats associated with the use of NSAIDs in the treatment of prostatic diseases. Hitoshi Ishiguro and Takashi Kawahara Copyright © 2014 Hitoshi Ishiguro and Takashi Kawahara. All rights reserved. Evidence for Bladder Urothelial Pathophysiology in Functional Bladder Disorders Thu, 08 May 2014 09:35:27 +0000 http://www.hindawi.com/journals/bmri/2014/865463/ Understanding of the role of urothelium in regulating bladder function is continuing to evolve. While the urothelium is thought to function primarily as a barrier for preventing injurious substances and microorganisms from gaining access to bladder stroma and upper urinary tract, studies indicate it may also function in cell signaling events relating to voiding function. This review highlights urothelial abnormalities in bladder pain syndrome/interstitial cystitis (BPS/IC), feline interstitial cystitis (FIC), and nonneurogenic idiopathic overactive bladder (OAB). These bladder conditions are typified by lower urinary tract symptoms including urinary frequency, urgency, urgency incontinence, nocturia, and bladder discomfort or pain. Urothelial tissues and cells from affected clinical subjects and asymptomatic controls have been compared for expression of proteins and mRNA. Animal models have also been used to probe urothelial responses to injuries of the urothelium, urethra, or central nervous system, and transgenic techniques are being used to test specific urothelial abnormalities on bladder function. BPS/IC, FIC, and OAB appear to share some common pathophysiology including increased purinergic, TRPV1, and muscarinic signaling, increased urothelial permeability, and aberrant urothelial differentiation. One challenge is to determine which of several abnormally regulated signaling pathways is most important for mediating bladder dysfunction in these syndromes, with a goal of treating these conditions by targeting specific pathophysiology. Susan K. Keay, Lori A. Birder, and Toby C. Chai Copyright © 2014 Susan K. Keay et al. All rights reserved. Bladder Cancer and Urothelial Impairment: The Role of TRPV1 as Potential Drug Target Thu, 08 May 2014 06:40:58 +0000 http://www.hindawi.com/journals/bmri/2014/987149/ Urothelium, in addition to its primary function of barrier, is now understood to act as a complex system of cell communication that exhibits specialized sensory properties in the regulation of physiological or pathological stimuli. Furthermore, it has been hypothesized that bladder inflammation and neoplastic cell growth, the two most representative pathological conditions of the lower urinary tract, may arise from a primary defective urothelial lining. Transient receptor potential vanilloid channel 1 (TRPV1), a receptor widely distributed in lower urinary tract structures and involved in the physiological micturition reflex, was described to have a pathophysiological role in inflammatory conditions and in the genesis and development of urothelial cancer. In our opinion new compounds, such as curcumin, the major component of turmeric Curcuma longa, reported to potentiate the effects of the chemotherapeutic agents used in the management of recurrent urothelial cancer in vitro and also identified as one of several compounds to own the vanillyl structure required to work like a TRPV1 agonist, could be thought as complementary in the clinical management of both the recurrences and the inflammatory effects caused by the endoscopic resection or intravesical chemotherapy administration or could be combined with adjuvant agents to potentiate their antitumoral effect. Francesco Mistretta, Nicolò Maria Buffi, Giovanni Lughezzani, Giuliana Lista, Alessandro Larcher, Nicola Fossati, Alberto Abrate, Paolo Dell’Oglio, Francesco Montorsi, Giorgio Guazzoni, and Massimo Lazzeri Copyright © 2014 Francesco Mistretta et al. All rights reserved. Neovaginal Prolapse in Male-to-Female Transsexuals: An 18-Year-Long Experience Wed, 07 May 2014 13:48:10 +0000 http://www.hindawi.com/journals/bmri/2014/240761/ Neovaginal prolapse is a rare and distressing complication after male-to-female sexual reassignment surgery. We retrospectively analysed the prevalence of partial and total neo-vaginal prolapses after sexual reassignment surgery in our institute. During the years, two different techniques have been adopted with the aim of fixing the neovaginal cylinder. In the first, two absorbable sutures are placed at the top of the penoscrotal cylinder and fixed to the Denonvilliers fascia. In the second, two additional sutures are added from the posterior/midpoint of the flap to the prerectal fascia. We enrolled 282 consecutive transsexual patients. 65 (23.04%) out of the 282 were treated with the first technique and the following 217 (76.96%) with the last technique. In the first technique, 1 case (1.53%) of total prolapse and 7 cases (10.76%) of partial prolapse were observed, while in the other 217 patients treated with the second technique only 9 cases of partial prolapse were observed (4.14%) and no cases of total prolapse. All prolapses occurred within 6 months from the procedure. In our experience, the use of 4 stitches and a more proximal positioning of the sutures to fix the penoscrotal apex with the Denonvilliers fascia guarantees a lower risk of prolapse. Stefano Bucci, Giorgio Mazzon, Giovanni Liguori, Renata Napoli, Nicola Pavan, Susanna Bormioli, Giangiacomo Ollandini, Bernardino De Concilio, and Carlo Trombetta Copyright © 2014 Stefano Bucci et al. All rights reserved. Cystitis: From Urothelial Cell Biology to Clinical Applications Wed, 30 Apr 2014 12:44:03 +0000 http://www.hindawi.com/journals/bmri/2014/473536/ Cystitis is a urinary bladder disease with many causes and symptoms. The severity of cystitis ranges from mild lower abdominal discomfort to life-threatening haemorrhagic cystitis. The course of disease is often chronic or recurrent. Although cystitis represents huge economical and medical burden throughout the world and in many cases treatments are ineffective, the mechanisms of its origin and development as well as measures for effective treatment are still poorly understood. However, many studies have demonstrated that urothelial dysfunction plays a crucial role. In the present review we first discuss fundamental issues of urothelial cell biology, which is the core for comprehension of cystitis. Then we focus on many forms of cystitis, its current treatments, and advances in its research. Additionally we review haemorrhagic cystitis with one of the leading causative agents being chemotherapeutic drug cyclophosphamide and summarise its management strategies. At the end we describe an excellent and widely used animal model of cyclophosphamide induced cystitis, which gives researches the opportunity to get a better insight into the mechanisms involved and possibility to develop new therapy approaches. Gilho Lee, Rok Romih, and Daša Zupančič Copyright © 2014 Gilho Lee et al. All rights reserved. Significance of Chromosome 9p Status in Renal Cell Carcinoma: A Systematic Review and Quality of the Reported Studies Wed, 30 Apr 2014 08:15:14 +0000 http://www.hindawi.com/journals/bmri/2014/521380/ Defining the prognosis of renal cell carcinoma (RCC) using genetic tests is an evolving area. The prognostic significance of 9p status in RCC, although described in the literature, remains underutilised in clinical practice. The study explored the causes of this translational gap. A systematic review on the significance of 9p status in RCC was performed to assess its clinical applicability and impact on clinical decision-making. Medline, Embase, and other electronic searches were made for studies reporting on 9p status in RCC. We collected data on: genetic techniques, pathological parameters, clinical outcomes, and completeness of follow-up assessment. Eleven studies reporting on 1,431 patients using different genetic techniques were included. The most commonly used genetic technique for the assessment of 9p status in RCC was fluorescence in situ hybridization. Combined genomic hybridisation (CGH), microsatellite analysis, karyotyping, and sequencing were other reported techniques. Various thresholds and cut-off values were used for the diagnosis of 9p deletion in different studies. Standardization, interobserver agreement, and consensus on the interpretation of test remained poor. The studies lacked validation and had high risk of bias and poor clinical applicability as assessed by two independent reviewers using a modified quality assessment tool. Further protocol driven studies with standardised methodology including use of appropriate positive and negative controls, assessment of interobserver variations, and evidenced based follow-up protocols are needed to clarify the role of 9p status in predicting oncological outcomes in renal cell cancer. Ismail El-Mokadem, John Fitzpatrick, Bhavan Rai, J. Cunningham, Norman Pratt, Stewart Fleming, and Ghulam Nabi Copyright © 2014 Ismail El-Mokadem et al. All rights reserved. Correlation between Urothelial Differentiation and Sensory Proteins P2X3, P2X5, TRPV1, and TRPV4 in Normal Urothelium and Papillary Carcinoma of Human Bladder Sun, 27 Apr 2014 13:58:18 +0000 http://www.hindawi.com/journals/bmri/2014/805236/ Terminal differentiation of urothelium is a prerequisite for blood-urine barrier formation and enables normal sensory function of the urinary bladder. In this study, urothelial differentiation of normal human urothelium and of low and high grade papillary urothelial carcinomas was correlated with the expression and localization of purinergic receptors (P2X3, and P2X5) and transient receptor potential vanilloid channels (TRPV1, and TRPV4). Western blotting and immunofluorescence of uroplakins together with scanning electron microscopy of urothelial apical surface demonstrated terminal differentiation of normal urothelium, partial differentiation of low grade carcinoma, and poor differentiation of high grade carcinoma. P2X3 was expressed in normal urothelium as well as in low grade carcinoma and in both cases immunolabeling was stronger in the superficial cells. P2X3 expression decreased in high grade carcinoma. P2X5 expression was detected in normal urothelium and in high grade carcinoma, while in low grade carcinoma its expression was diminished. The expression of TRPV1 decreased in low grade and even more in high grade carcinoma when compared with normal urothelium, while TRPV4 expression was unchanged in all samples. Our results suggest that sensory proteins P2X3 and TRPV1 are in correlation with urothelial differentiation, while P2X5 and TRPV4 have unique expression patterns. Igor Sterle, Daša Zupančič, and Rok Romih Copyright © 2014 Igor Sterle et al. All rights reserved. Effect of Inflammatory Mediators on ATP Release of Human Urothelial RT4 Cells Tue, 15 Apr 2014 11:29:49 +0000 http://www.hindawi.com/journals/bmri/2014/182862/ Inflammation is an important contributor to the aetiology of a number of bladder dysfunctions including interstitial cystitis, painful bladder syndrome, and overactive bladder. The aim of this study was to examine the effects of inflammatory mediators on urothelial ATP release. Human urothelial RT4 cells were exposed to normal buffer or varying concentrations of inflammatory mediators (bradykinin, histamine, and serotonin) in the presence or absence of hypotonic stretch stimuli (1 : 2 dilution of Krebs-Henseleit buffer). Others have demonstrated that bradykinin increased stretch-induced ATP release; however, we observed no change in control or stretch-induced ATP release with bradykinin. Pretreatment of RT4 cells with histamine or serotonin decreased stretch-induced ATP release (, , resp.). Previous studies have demonstrated increased ATP release in response to inflammation utilising whole bladder preparations in contrast to our simple model of cultured urothelial cells. The current study suggests that it is unlikely that there is a direct interaction between the release of inflammatory mediators and increased ATP release, but rather more complex interactions occurring in response to inflammation that lead to increased bladder sensation. Kylie J. Mansfield and Jessica R. Hughes Copyright © 2014 Kylie J. Mansfield and Jessica R. Hughes. All rights reserved. Nonkeratinised Squamous Metaplasia of the Urinary Bladder in Children: A Report of Case Experiences Tue, 15 Apr 2014 00:00:00 +0000 http://www.hindawi.com/journals/bmri/2014/936970/ Background. Squamous metaplasia refers to the pathological transformation of the urothelium leading to nonkeratinised stratified squamous metaplasia (N-KSM). Objective. To present our experiences in the diagnosis and treatment of N-KSM of the urinary bladder in children. Materials and Methods. In this study, we present our experiences in the diagnosis and treatment of N-KSM of the urinary bladder in children aged from 5 to 17 years. From 2005 to 2013, metaplasia was diagnosed in 119 patients. The reasons behind visiting the hospital were nonspecific intense pain in the abdomen, recurrent urinary tract infections, and urination disorders. The most common symptoms of urinary bladder dysfunction were pollakiuria and difficulties in initiating micturition and retention of urine (reduced detrusor muscle activity). Results. In 20/119 patients (16.8%), metaplasia was incidentally diagnosed during cystoscopy performed for other causes. The changes characteristic for squamous metaplasia were diagnosed—in all these patients, a biopsy was performed. In all 119 patients, a squamous metaplasia was histopathologically diagnosed. Conclusions. Squamous metaplasia of the urinary bladder mucosa occurs in children and adolescents. Symptomatic treatment is administered mainly to improve the patients’ quality of life and disease prognosis. Beata Jurkiewicz and Tomasz Ząbkowski Copyright © 2014 Beata Jurkiewicz and Tomasz Ząbkowski. All rights reserved. Alterations of the Myovesical Plexus of the Human Overactive Detrusor Tue, 15 Apr 2014 00:00:00 +0000 http://www.hindawi.com/journals/bmri/2014/754596/ Objectives. The human bladder shows spontaneous autonomous activity. Detrusor overactivity could be seen as a consequence of exaggerated autonomous activity. Interstitial cells (ICs) play a potential role in coordination of autonomous activity. As it is suggested that changes in ICs coexist with detrusor overactivity (DO), we investigated possible alterations to human bladder ICs. Methods. Biopsies were obtained from 23 patients and were categorized into four groups: genuine stress incontinence (without DO) (), neurogenic disease with DO (), bladder outlet obstruction with DO (), or idiopathic DO (). Specimens were processed to investigate expression of N-cadherin and PGP9.5. N-cadherin expression was semiquantitatively analyzed and correlated to PG9.5 expression and bladder wall morphology. Results. The population of cells expressing N-cadherin is altered in the overactive detrusor, making no difference between the sources of DO. Punctate distribution of morphological changes was found and downregulation of PGP9.5 expression seemed to coexist with upregulation of N-cadherin expression in the detrusor layer. Conclusions. The population of N-cadherin+ cells of the interstitial compartment of the human bladder has the ability to proliferate. As this proliferation seems to coexist with denervation, it could be possible that a highly developed network of interstitial cells replaces the loss of innervation in overactive detrusor. Kamiel A. J. Kuijpers, John P. F. A. Heesakkers, and Jack A. Schalken Copyright © 2014 Kamiel A. J. Kuijpers et al. All rights reserved. P2Y Receptor Modulation of ATP Release in the Urothelium Mon, 14 Apr 2014 17:21:01 +0000 http://www.hindawi.com/journals/bmri/2014/830374/ The release of ATP from the urothelium in response to stretch during filling demonstrates the importance of the purinergic system for the physiological functioning of the bladder. This study examined the effect of P2 receptor agonists on ATP release from two urothelial cell lines (RT4 and UROtsa cells). Hypotonic Krebs was used as a stretch stimulus. Incubation of urothelial cells with high concentrations of the P2Y agonist ADP induced ATP release to a level that was 40-fold greater than hypotonic-stimulated ATP release (P < 0.0011, ADP EC50 1.8 µM). Similarly, an increase in ATP release was also observed with the P2Y agonist, UTP, up to a maximum of 70% of the hypotonic response (EC50 0.62 µM). Selective P2 receptor agonists, αβ-methylene-ATP, ATP-γ-S, and 2-methylthio-ADP had minimal effects on ATP release. ADP-stimulated ATP release was significantly inhibited by suramin (100 µM, P = 0.002). RT4 urothelial cells break down nucleotides (100 µM) including ATP, ADP, and UTP to liberate phosphate. Phosphate liberation was also demonstrated from endogenous nucleotides with approximately 10% of the released ATP broken down during the incubation. These studies demonstrate a role for P2Y receptor activation in stimulation of ATP release and emphasize the complexity of urothelial P2 receptor signalling. Kylie J. Mansfield and Jessica R. Hughes Copyright © 2014 Kylie J. Mansfield and Jessica R. Hughes. All rights reserved. Urinary Angiotensinogen Is Elevated in Patients with Nephrolithiasis Wed, 09 Apr 2014 07:15:46 +0000 http://www.hindawi.com/journals/bmri/2014/349602/ Background. Elevated urinary angiotensinogen (UA) was identified as novel prognostic biomarker capable of predicting chronic kidney disease, and in the present study, we will investigate the diagnostic value of UA in the patients of nephrolithiasis. Methods. Urine angiotensinogen levels and α1-microglobulin were measured by enzyme-linked immunosorbent assay (ELISA) in 60 patients presenting with nephrolithiasis and 50 sex- and age-matched healthy volunteers. Estimated glomerular filtration (eGFR) was calculated and, by simple regression analysis, the correlation of UA/α1-microglobulin levels and the decline of eGFR were analyzed as well. Results. Median UA levels was significantly increased in the nephrolithiasis patients compared with normal control (1250.78 439.27 versus 219.34 45.27 pg/mL; ). The mean serum creatinine levels in patients with higher UA levels (1250 pg/mL) was significantly higher than those with lower UA levels (1250 pg/mL) [92.23 18.13 μmol/L versus 70.07 11.17 μmol/L; ]. According to the single variate analysis, UA levels were significantly and positively correlated with urinary α1-microglobulin (; ), while they were significantly and negatively correlated with eGFR (; ). Conclusion. Urinary UA is a novel biomarker for patients with nephrolithiasis, which indicates renal tubular injury. Further study on the molecular pathogenic mechanism of UA and larger scale of clinical trial is required. Wei Sun, Yuan Feng, Xu-Dong Yao, Yun-Fei Xu, Bo Peng, Min Liu, and Jun-Hua Zheng Copyright © 2014 Wei Sun et al. All rights reserved. Kallikreins as Biomarkers for Prostate Cancer Mon, 07 Apr 2014 07:09:08 +0000 http://www.hindawi.com/journals/bmri/2014/526341/ The introduction of testing for prostate-specific antigen (PSA), a member of the fifteen-gene family of kallikrein-related peptidases and also known as kallikrein-related peptidase 3 (KLK3), in blood has revolutionized both the detection and management of prostate cancer. Given the similarities between PSA and other KLK gene family members along with limitations of PSA as a biomarker for prostate cancer mainly in reference to diagnostic specificity, the potential roles of other members of this gene family as well as PSA derivatives and isoforms in the management of prostate cancer have been studied extensively. Of these, approaches to measure distinct molecular forms of PSA (free, intact, complexed PSA, and pro-PSA) combined with kallikrein-related peptidase 2 (KLK2), also known as hK2, have been considered holding particular promise in enhancing the diagnosis of prostate cancer. Recently, an integrated approach of applying a panel of four kallikrein markers has been demonstrated to enhance accuracy in predicting the risk of prostate cancer at biopsy. This review presents an overview of kallikreins, starting with the past and current status of PSA, summarizing published data on the evaluations of various KLKs as biomarkers in the diagnosis, prognostication, and monitoring of prostate cancer. Sung Kyu Hong Copyright © 2014 Sung Kyu Hong. All rights reserved. Inflammatory Reaction as Determinant of Foreign Body Reaction Is an Early and Susceptible Event after Mesh Implantation Wed, 26 Mar 2014 00:00:00 +0000 http://www.hindawi.com/journals/bmri/2014/510807/ Purpose. To investigate and relate the ultrashort-term and long-term courses of determinants for foreign body reaction as biocompatibility predictors for meshes in an animal model. Materials and Methods. Three different meshes (TVT, UltraPro, and PVDF) were implanted in sheep. Native and plasma coated meshes were placed bilaterally: (a) interaperitoneally, (b) as fascia onlay, and (c) as muscle onlay (fascia sublay). At 5 min, 20 min, 60 min, and 120 min meshes were explanted and histochemically investigated for inflammatory infiltrate, macrophage infiltration, vessel formation, myofibroblast invasion, and connective tissue accumulation. The results were related to long-term values over 24 months. Results. Macrophage invasion reached highest extents with up to 60% in short-term and decreased within 24 months to about 30%. Inflammatory infiltrate increased within the first 2 hours, the reached levels and the different extents and ranking among the investigated meshes remained stable during long-term follow up. For myofibroblasts, connective tissue, and CD31+ cells, no activity was detected during the first 120 min. Conclusion. The local inflammatory reaction is an early and susceptible event after mesh implantation. It cannot be influenced by prior plasma coating and does not depend on the localisation of implantation. Holger Gerullis, Evangelos Georgas, Mihaly Borós, Bernd Klosterhalfen, Christoph Eimer, Christian Arndt, Stephan Otto, Dimitri Barski, Dirk Ysebaert, Albert Ramon, and Thomas Otto Copyright © 2014 Holger Gerullis et al. All rights reserved. Bioenergetics of Mammalian Sperm Capacitation Tue, 25 Mar 2014 13:26:51 +0000 http://www.hindawi.com/journals/bmri/2014/902953/ After ejaculation, the mammalian male gamete must undergo the capacitation process, which is a prerequisite for egg fertilization. The bioenergetics of sperm capacitation is poorly understood despite its fundamental role in sustaining the biochemical and molecular events occurring during gamete activation. Glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) are the two major metabolic pathways producing ATP which is the primary source of energy for spermatozoa. Since recent data suggest that spermatozoa have the ability to use different metabolic substrates, the main aim of this work is to present a broad overview of the current knowledge on the energy-producing metabolic pathways operating inside sperm mitochondria during capacitation in different mammalian species. Metabolism of glucose and of other energetic substrates, such as pyruvate, lactate, and citrate, is critically analyzed. Such knowledge, besides its obvious importance for basic science, could eventually translate into the development of novel strategies for treatment of male infertility, artificial reproduction, and sperm selection methods. Alessandra Ferramosca and Vincenzo Zara Copyright © 2014 Alessandra Ferramosca and Vincenzo Zara. All rights reserved. Disturbances of Sperm Maturation and Minipuberty: Is There a Connection? Thu, 13 Mar 2014 00:00:00 +0000 http://www.hindawi.com/journals/bmri/2014/912746/ Male reproductive function in the general population raises an increased attention due to reports indicating declining sperm counts, increased occurrence of testicular cancer, cryptorchidism, and hypospadias. It is also hypothesized that prolonged exposure of the developing male, during both fetal and postnatal life, to exogenous estrogens could reduce Sertoli cell number and thus reduce sperm output (and sperm counts) in adult life. Fact is that infertility, which is defined as the inability to conceive after 1 year of unprotected intercourse, has a global prevalence of 9%. A male contributory factor is involved in approximately half of these cases, but most of the causes of reduced semen quality and other disturbances of male reproductive function are unknown. In the most affected men (azoospermic men) 15–20% had a prior history of cryptorchidism. The association between the cryptorchidism and infertility is one of the most studied potential causes of infertility. There are numerous studies that accentuate the importance of minipuberty for future fertility. Is it possible that a normal minipuberty ensures normal fertility despite malpositioned testes? And to move away from cryptorchidism, could impaired minipuberty be responsible for fertility problems in men who were born with both testes in their scrotal sacs? D. Živković and I. Fratrić Copyright © 2014 D. Živković and I. Fratrić. All rights reserved. The Role(s) of Cytokines/Chemokines in Urinary Bladder Inflammation and Dysfunction Wed, 12 Mar 2014 00:00:00 +0000 http://www.hindawi.com/journals/bmri/2014/120525/ Bladder pain syndrome (BPS)/interstitial cystitis (IC) is a chronic pain syndrome characterized by pain, pressure, or discomfort perceived to be bladder related and with at least one urinary symptom. It was recently concluded that 3.3–7.9 million women (>18 years old) in the United States exhibit BPS/IC symptoms. The impact of BPS/IC on quality of life is enormous and the economic burden is significant. Although the etiology and pathogenesis of BPS/IC are unknown, numerous theories including infection, inflammation, autoimmune disorder, toxic urinary agents, urothelial dysfunction, and neurogenic causes have been proposed. Altered visceral sensations from the urinary bladder (i.e., pain at low or moderate bladder filling) that accompany BPS/IC may be mediated by many factors including changes in the properties of peripheral bladder afferent pathways such that bladder afferent neurons respond in an exaggerated manner to normally innocuous stimuli (allodynia). The goals for this review are to describe chemokine/receptor (CXCL12/CXCR4; CCL2/CCR2) signaling and cytokine/receptor (transforming growth factor (TGF-β)/TGF-β type 1 receptor) signaling that may be valuable LUT targets for pharmacologic therapy to improve urinary bladder function and reduce somatic sensitivity associated with urinary bladder inflammation. Eric J. Gonzalez, Lauren Arms, and Margaret A. Vizzard Copyright © 2014 Eric J. Gonzalez et al. All rights reserved. Microscopic Varicocelectomy Significantly Decreases the Sperm DNA Fragmentation Index in Patients with Infertility Mon, 10 Mar 2014 09:14:02 +0000 http://www.hindawi.com/journals/bmri/2014/695713/ Background. Varicocele is associated with high levels of DNA damage in spermatozoa due to oxidative stress and elevated levels of sperm DNA fragmentation, which has been currently proposed to be an essential additional diagnostic test to be recommended for patients with clinical varicocele. The aim of this study was to evaluate the parameters of semen and the DNA fragmentation index (DFI) in patients with varicocele before and after varicocelectomy. Methods. The details of 92 consecutive patients were retrospectively analyzed from January 2010 to December 2012. The sperm samples were evaluated according to the World Health Organization Guidelines. Sperm DNA damage, characterized as DFI, was evaluated by sperm chromatin structure assay using flow cytometry. Results. There was a statistically significant improvement in the semen concentration, the total motile count, the total normal sperm count, and the sperm DNA fragmentation index (DFI; the percentage of sperm with denatured DNA) after varicocelectomy. There was a large decrease in DFI from a preoperative mean of 42.6% to a postoperative mean of 20.5% (). A higher preoperative DFI was associated with a larger decrease in postoperative DFI, and significant negative correlations were observed between the DFI and sperm motility (, ). Conclusion. Our data suggest that varicocelectomy can improve multiple semen parameters and sperm DNA damage in infertile men with varicocele. The patients with preoperative defects in those parameters showed greater improvement postoperatively. Further research in this area is needed to understand the exact mechanisms of DNA damage in infertile men with varicocele. Teoman Cem Kadioglu, Emin Aliyev, and Murad Celtik Copyright © 2014 Teoman Cem Kadioglu et al. All rights reserved. The Dynamic of the Apical Ectoplasmic Specialization between Spermatids and Sertoli Cells: The Case of the Small GTPase Rap1 Thu, 27 Feb 2014 09:01:19 +0000 http://www.hindawi.com/journals/bmri/2014/635979/ Despite advances in assisted reproductive technologies, infertility remains a consistent health problem worldwide. Spermiation is the process through which mature spermatids detach from the supporting Sertoli cells and are released into the tubule lumen. Spermiation failure leads to lack of mature spermatozoa and, if not occasional, could result into azoospermia, major cause of male infertility in human population. Spermatids are led through their differentiation into spermatozoa by the apical ectoplasmic specialization (aES), a testis-specific, actin-based anchoring junction restricted to the Sertoli-spermatid interface. The aES helps spermatid movement across the seminiferous epithelium, promotes spermatid positioning, and prevents the release of immature spermatozoa. To accomplish its functions, aES needs to undergo tightly and timely regulated restructuring. Even if components of aES are partly known, the mechanism/s through which aES is regulated remains still elusive. In this review, we propose a model by which the small GTPase Rap1 could regulate aES assembly/remodelling. The characterization of key players in the dynamic of aES, such as Rap1, could open new possibility to develop prognostic, diagnostic, and therapeutic approaches for male patients under treatment for infertility as well as it could lead to the identification of new target for male contraception. Giovanna Berruti and Chiara Paiardi Copyright © 2014 Giovanna Berruti and Chiara Paiardi. All rights reserved. An Update of the Interstitial Cell Compartment in the Normal Human Bladder Thu, 27 Feb 2014 06:34:56 +0000 http://www.hindawi.com/journals/bmri/2014/464217/ Aims. Interstitial cells, also called myofibroblasts, most probably play a major role in the pathogenesis of the overactive bladder. However, no specific phenotypic marker has been identified. We investigated whether N-cadherin could play a role as a discriminatory marker for interstitial cells in the human bladder. Methods. Bladder biopsies (n = 16) were collected from macroscopically nonpathological locations during cystectomy which was performed because of bladder cancer. Tissue was analyzed for expression of N-cadherin. N-cadherin+ cells were phenotyped using antibodies against PGP9.5, smoothelin, vimentin, and C-kit. Findings were related to bladder tissue histology and ultrastructure of myofibroblastic cells. Results. N-cadherin+/vimentin+ cells with branched cell bodies were found in the lamina propria and detrusor layer. They were closely associated with neurons and showed no colocalization of PGP9.5 or smoothelin. A second type of N-cadherin+ cells was found at the boundary of detrusor bundles and in the lamina propria. These cells colocalization C-kit. We assumed that N-cadherin+/vimentin+ cells are similar to the ultrastructurally defined myofibroblasts. Conclusions. N-cadherin can play a role as a discriminatory marker for interstitial cells in the human bladder, as the interstitial compartment of the human bladder houses a population of cells from mesenchymal origin, immunopositive for N-cadherin, vimentin, and C-kit. Kamiel A. J. Kuijpers, John P. F. A. Heesakkers, Theo G. M. Hafmans, and Jack A. Schalken Copyright © 2014 Kamiel A. J. Kuijpers et al. All rights reserved. Characterization of Uptake and Internalization of Exosomes by Bladder Cancer Cells Sun, 19 Jan 2014 00:00:00 +0000 http://www.hindawi.com/journals/bmri/2014/619829/ Bladder tumors represent a special therapeutic challenge as they have a high recurrence rate requiring repeated interventions and may progress to invasive or metastatic disease. Exosomes carry proteins implicated in bladder cancer progression and have been implicated in bladder cancer cell survival. Here, we characterized exosome uptake and internalization by human bladder cancer cells using Amnis ImageStreamX, an image cytometer. Exosomes were isolated by ultracentrifugation from bladder cancer culture conditioned supernatant, labeled with PKH-26, and analyzed on the ImageStreamX with an internal standard added to determine concentration. Exosomes were cocultured with bladder cancer cells and analyzed for internalization. Using the IDEAS software, we determined exosome uptake based on the number of PKH-26+ spots and overall PKH-26 fluorescence intensity. Using unlabeled beads of a known concentration and size, we were able to determine concentrations of exosomes isolated from bladder cancer cells. We measured exosome uptake by recipient bladder cancer cells, and we demonstrated that uptake is dose and time dependent. Finally, we found that uptake is active and specific, which can be partially blocked by heparin treatment. The characterization of cellular uptake and internalization by bladder cancer cells may shed light on the role of exosomes on bladder cancer recurrence and progression. Carrie A. Franzen, Patricia E. Simms, Adam F. Van Huis, Kimberly E. Foreman, Paul C. Kuo, and Gopal N. Gupta Copyright © 2014 Carrie A. Franzen et al. All rights reserved. The CFTR M470V, Intron 8 Poly-T, and 8 TG-Repeats Detection in Chinese Males with Congenital Bilateral Absence of the Vas Deferens Wed, 08 Jan 2014 15:59:43 +0000 http://www.hindawi.com/journals/bmri/2014/689185/ Purpose. To evaluate the significance of molecular detection of cystic fibrosis transmembrane conductance regulator (CFTR) M470V, intron 8 poly-T, and intron 8 TG-repeats in congenital bilateral absence of the vas deferens (CBAVD). Methods. Eighty-nine male patients with CBAVD and 103 healthy males were included in this study. Polymerase chain reaction was performed to amplify the polymorphic regions using primers from conserved regions. M470V was genotyped using real-time PCR by cycling probe. The exon 9 DNA sequence was determined using an automated sequencer. TG-repeats and poly-T were identified by direct sequencing analysis. Results. The 5T allele distribution was 0.32, 0.66 for 7T, and 0.02 for 9T in CBAVD males, respectively. In contrast, the 5T allele distribution was 0.03, 0.96 for 7T, and 0.01 for 9T in healthy control. Study of the polymorphisms of the upstream of exon 9 revealed a higher frequency of 5T allele in the CBAVD males. All cases with TG13T5 haplotype and TG12T5 homozygous led to CBAVD. The CFTR TG12T5-V470 variant haplotype was associated with CBAVD. Conclusion. The 5T allele of intron 8 of CFTR has clinically significant association with CBAVD. TG13T5 and TG12T5 homozygously led to CBAVD, and TG12T5-V470 may also lead to CBAVD. Qiang Du, Zheng Li, Yongfeng Pan, Xiaoliang Liu, Bochen Pan, and Bin Wu Copyright © 2014 Qiang Du et al. All rights reserved. Cytokeratin 18 Is Not Required for Morphogenesis of Developing Prostates but Contributes to Adult Prostate Regeneration Mon, 30 Dec 2013 12:01:55 +0000 http://www.hindawi.com/journals/bmri/2013/576472/ Cytokeratin 18 (CK18) is a key component of keratin-containing intermediate filaments and has long been used as a classic luminal cell marker in prostatic tissue. However, the in vivo function of CK18 in prostate is not known so far. We reported in this study, unexpectedly, that deletion of CK18 in a mouse model did not affect the morphological or the histological structures of adult prostate, as the CK18 knockout prostate displayed a normal glandular ductal structure, branching pattern, and composition of both luminal and basal cells. However, CK18 loss compromised the regenerative tubular branching in dorsolateral prostate after castration and androgen replacement. Therefore, in contrast to its importance as luminal cell marker, CK18 is dispensable for the prostate morphogenesis but contributes to adult prostate regeneration. Chenlu Zhang, Yanjing Guo, Jian Cui, Helen He Zhu, and Wei-Qiang Gao Copyright © 2013 Chenlu Zhang et al. All rights reserved. Contrast Enhanced Ultrasound of the Kidneys: What Is It Capable of? Tue, 24 Dec 2013 16:57:18 +0000 http://www.hindawi.com/journals/bmri/2013/595873/ One of the many imaging uses of contrast enhanced ultrasound (CEUS) is studying a wide variety of kidney pathology, due to its ability to detect microvascular blood flow in real time without affecting renal function. CEUS enables dynamic assessment and quantification of microvascularisation up to capillary perfusion. The objective of this paper is to briefly refresh basic knowledge of ultrasound (US) contrast agents’ physical properties, to study technical details of CEUS scanning in the kidneys, and to review the commonest renal indications for CEUS, with imaging examples in comparison to baseline unenhanced US and computed tomography when performed. Safety matters and limitations of CEUS of the kidneys are also discussed. Demosthenes D. Cokkinos, Eleni G. Antypa, Maria Skilakaki, Despoina Kriketou, Ekaterini Tavernaraki, and Ploutarchos N. Piperopoulos Copyright © 2013 Demosthenes D. Cokkinos et al. All rights reserved. Introducing a Method of In Vitro Testing of Different Anchoring Systems Used for Female Incontinence and Prolapse Surgery Sun, 22 Dec 2013 10:54:42 +0000 http://www.hindawi.com/journals/bmri/2013/401417/ Aims. To develop a method for in vitro testing to compare different intracorporeal anchoring systems (AS) used, for example, in single-incision slings or vaginal meshes. Intracorporeal fixation needs reliable anchorage systems, which keep the implant in the operative and early postoperative phase in place. Up to now, the impact of the design of current anchor systems and their capability to provide sufficient retention forces is not known. Methods. Four AS (“PelFix”, “Surelift”, “TFS”, and “MiniArc”) were evaluated in an animal model and a ballistic gelatine model with pull-out tests. We performed ANOVA with post hoc Bonferroni. Results were presented as mean values whereby a significance level of <0.05 was considered significant. Results. The four systems showed significantly different pull-out forces. Depending on mesh structure, size, and form of the AS, mechanical strain resulted in deformation with local peak stresses. Under the condition of form stability, relative differences of pull-out forces did not change in different tissues. Conclusions. Reliable testing of different AS in their ability to keep mesh implants in place can be done in animal models and in especially designed ballistic gelatine. These methods of testing will help to modify AS in novel pelvic floor implants. Ralf Anding, Ruth Tabaza, Manfred Staat, Eva Trenz, Philipp Lohmann, Uwe Klinge, and Ruth Kirschner-Hermanns Copyright © 2013 Ralf Anding et al. All rights reserved. Hemizona Assay and Sperm Penetration Assay in the Prediction of IVF Outcome: A Systematic Review Mon, 21 Oct 2013 14:47:04 +0000 http://www.hindawi.com/journals/bmri/2013/945825/ The limited predictive value of semen analysis in achieving natural conception or in IVF outcome confirms the need for sperm function tests to determine optimal management. We reviewed HZA and SPA predictive power in IVF outcome, with statistical significance of diagnostic power of the assays. HZA was readily efficient in predicting IVF outcome, while evident inconsistency among the studies analysed framed the SPA’s role in male fertility evaluation. Considerable variation was noted in the diagnostic accuracy values of SPA with wide sensitivity (52–100%), specificity (0–100%), and PPV (18–100%) and NPV (0–100%) together with fluctuation and notable differentiation in methodology and cutoff values employed by each group. HZA methodology was overall consistent with minor variation in cutoff values and oocyte source, while data analysis reported strong correlation between HZA results with IVF outcome, high sensitivity (75–100%), good specificity (57–100%), and high PPV (79–100%) and NPV (68–100%). HZA correlated well with IVF outcome and demonstrated better sensitivity/specificity and positive/negative predictive power. Males with normal or slightly abnormal semen profiles could benefit by this intervention and could be evaluated prior to referral to assisted reproduction. HZA should be used in a sequential fashion with semen analysis and potentially other bioassays in an IVF setting. Paraskevi Vogiatzi, Charalampos Chrelias, David J. Cahill, Maria Creatsa, Nikos Vrachnis, Zoe Iliodromiti, Demetrios Kassanos, and Charalampos Siristatidis Copyright © 2013 Paraskevi Vogiatzi et al. All rights reserved. Alpha-Lipoic Acid Attenuates Renal Injury in Rats with Obstructive Nephropathy Thu, 03 Oct 2013 18:11:52 +0000 http://www.hindawi.com/journals/bmri/2013/138719/ This study was established to determine the possible protective effects of alpha-lipoic acid (ALA), a powerful antioxidant, on renal injury in obstructive nephropathy. Male Sprague-Dawley rats were assigned into sham-operated unilateral ureteral obstruction (UUO) and UUO treated with ALA groups. ALA 60 mg/kg was injected intraperitoneally 2 days before UUO induction and continued afterward for 7 days. Renal function, oxidative stress markers, nitric oxide, transforming growth factor-1 (TGF-β1), and histological changes were evaluated at the end of the experiment. Obstruction of the ureter resulted in renal dysfunction as indicated by significant increases in blood urea nitrogen and serum creatinine. Nonobstructed contralateral kidneys in all groups examined did not show any morphological or biochemical alterations. In untreated UUO group, the obstructed kidney developed marked hydronephrosis, leukocyte infiltration, and severe interstitial fibrosis. These functional and structural changes were associated with significant increases in tissue levels of malondialdehyde, nitric oxide, and TGF-β1 but decreases in reduced glutathione and total antioxidant capacity. Pretreatment with ALA significantly minimized all the changes elicited by ureteral obstruction. These findings demonstrate that ALA supplementation attenuates renal injury in rats with obstructive nephropathy and further suggest that oxidative stress inhibition is likely to be involved in the beneficial effects of this compound. Orawan Wongmekiat, Dolrawee Leelarungrayub, and Kamthorn Thamprasert Copyright © 2013 Orawan Wongmekiat et al. All rights reserved. Factors Influencing Women's Decision to Participate or Not in a Surgical Randomised Controlled Trial for Surgical Treatment of Female Stress Urinary Incontinence Tue, 17 Sep 2013 18:20:58 +0000 http://www.hindawi.com/journals/bmri/2013/139813/ The study aims to explore the potentially influential factors affecting women's decision to accept/decline participation in surgical randomised trial using a novel acceptance/refusal questionnaire (ARQ). All women who were eligible to participate in SIMS-RCT were asked to complete the relevant section (acceptance/refusal) of the ARQ. Women reported its degree of relevance for their decision on a six-point Likert scale (0 = highly irrelevant, 5 = highly relevant). 135 (98%) and 31 (70%) women completed the acceptance and refusal sections of the ARQ, respectively. The most influencing factor in women’s acceptance was the anticipation of “potential personal benefit”; percentage of relevance (POR) was 91.9%, followed by interest in helping others by “supporting innovative medical research”; POR was 87.7%. Most influencing factor in refusal for participation was “do not have time for follow-up”; POR was 56.8%, followed by “do not like the concept of randomisation”; POR was 54.4%. In conclusion, this study identifies the most influential factors relevant to women decision-making whether or not to participate in RCTs assessing surgical interventions for female stress urinary incontinence (SUI). A number of factors leading to refusal of participation are potentially correctable leading to better recruitment rates in future RCTs. Alyaa Mostafa, James N'Dow, and Mohamed Abdel-Fattah Copyright © 2013 Alyaa Mostafa et al. All rights reserved. Coating with Autologous Plasma Improves Biocompatibility of Mesh Grafts In Vitro: Development Stage of a Surgical Innovation Tue, 17 Sep 2013 18:16:15 +0000 http://www.hindawi.com/journals/bmri/2013/536814/ Purpose. To investigate mesh coating modalities with autologous blood components in a recently developed in vitro test system for biocompatibility assessment of alloplastic materials. Materials and Methods. Seven different mesh types, currently used in various indications, were randomly investigated. Meshes were coated prior to cultivation with autologous peripheral blood mononuclear cells (PBMCs), platelets, and blood plasma. Pretreated meshes were incubated over 6 weeks in a minced tissue assay, representative for fibroblasts, muscle cells, and endothelial cells originating from 10 different patients. Adherence of those tissues on the meshes was microscopically investigated and semiquantitatively assessed using a previously described scoring system. Results. Coating with peripheral blood mononuclear cells did not affect the adherence score, whereas coating with platelets and blood plasma increased the score suggesting improved biocompatibility in vitro. The previous ranking of native meshes remained consistent after coating. Conclusion. Plasma coating of meshes improves their biocompatibility score in a novel in vitro test system. Holger Gerullis, Evangelos Georgas, Christoph Eimer, Christian Arndt, Dimitri Barski, Bernhard Lammers, Bernd Klosterhalfen, Mihaly Borós, and Thomas Otto Copyright © 2013 Holger Gerullis et al. All rights reserved. Androgen Signaling Disruption during Fetal and Postnatal Development Affects Androgen Receptor and Connexin 43 Expression and Distribution in Adult Boar Prostate Tue, 17 Sep 2013 10:51:48 +0000 http://www.hindawi.com/journals/bmri/2013/407678/ To date, limited knowledge exists regarding the role of the androgen signaling during specific periods of development in the regulation of androgen receptor (AR) and connexin 43 (Cx43) in adult prostate. Therefore, in this study we examined mRNA and protein expression, and tissue distribution of AR and Cx43 in adult boar prostates following fetal (GD20), neonatal (PD2), and prepubertal (PD90) exposure to an antiandrogen flutamide (50 mg/kg bw). In GD20 and PD2 males we found the reduction of the luminal compartment, inflammatory changes, decreased AR and increased Cx43 expression, and altered localization of both proteins. Moreover, enhanced apoptosis and reduced proliferation were detected in the prostates of these animals. In PD90 males the alterations were less evident, except that Cx43 expression was markedly upregulated. The results presented herein indicate that in boar androgen action during early fetal and neonatal periods plays a key role in the maintenance of normal phenotype and functions of prostatic cells at adulthood. Furthermore, we demonstrated that modulation of Cx43 expression in the prostate could serve as a sensitive marker of hormonal disruption during different developmental stages. Anna Hejmej, Ewelina Górowska, Małgorzata Kotula-Balak, Katarzyna Chojnacka, Marta Zarzycka, Justyna Zając, and Barbara Bilińska Copyright © 2013 Anna Hejmej et al. All rights reserved. Progress of Molecular Targeted Therapies for Advanced Renal Cell Carcinoma Wed, 04 Sep 2013 14:48:52 +0000 http://www.hindawi.com/journals/bmri/2013/419176/ Vascular endothelial growth factor (VEGF) plays a crucial role in tumor angiogenesis. VEGF expression in metastatic renal cell carcinoma (mRCC) is mostly regulated by hypoxia, predominantly via the hypoxia-induced factor (HIF)/Von Hippel-Lindau (VHL) pathway. Advances in our knowledge of VEGF role in tumor angiogenesis, growth, and progression have permitted development of new approaches for the treatment of mRCC, including several agents targeting VEGF and VEGF receptors: tyrosine kinase pathway, serine/threonine kinases, α5β1-integrin, deacetylase, CD70, mammalian target of rapamycin (mTOR), AKT, and phosphatidylinositol 3′-kinase (PI3K). Starting from sorafenib and sunitinib, several targeted therapies have been approved for mRCC treatment, with a long list of agents in course of evaluation, such as tivozanib, cediranib, and VEGF-Trap. Here we illustrate the main steps of tumor angiogenesis process, defining the pertinent therapeutic targets and the efficacy and toxicity profiles of these new promising agents. Alessandro Conti, Matteo Santoni, Consuelo Amantini, Luciano Burattini, Rossana Berardi, Giorgio Santoni, Stefano Cascinu, and Giovanni Muzzonigro Copyright © 2013 Alessandro Conti et al. All rights reserved. High Expression of H3K27me3 Is an Independent Predictor of Worse Outcome in Patients with Urothelial Carcinoma of Bladder Treated with Radical Cystectomy Wed, 04 Sep 2013 10:00:32 +0000 http://www.hindawi.com/journals/bmri/2013/390482/ It has been suggested that trimethylation of lysine 27 on histone H3 (H3K27me3) is a crucial epigenetic process in tumorigenesis. However, the expression pattern of H3K27me3 and its clinicopathological/prognostic significance in urothelial carcinoma of bladder (UCB) are unclear. In this study, upregulated expression of H3K27me3 protein was observed in the majority of UCBs by Western blotting. High expression of H3K27me3 was examined by IHC in 59/126 (46.8%) of UCB tissues and in 18/72 (25.0%) of normal urothelial bladder epithelial tissues (). High expression of H3K27me3 was associated with multifocal tumors and lymph node metastases (). Patients with high expression of H3K27me3 had shorter cancer-specific survival (CSS) time than patients with low expression of H3K27me3 (). In different subsets of UCB patients, high expression of H3K27me3 was also a prognostic indicator in patients with grade 2 and grade 3, pT1, pT2, pT3, and pN− disease (). Importantly, expression of H3K27me3 was an independent predictor for CSS () of UCB patients treated with radical cystectomy (RC). Our data suggests that high expression of H3K27me3 is an independent molecular marker for predicting poor prognosis of UCB patients treated with RC. Jianye Liu, Yonghong Li, Yiji Liao, Shijuan Mai, Zhiling Zhang, Zhouwei Liu, Lijuan Jiang, Yixin Zeng, Fangjian Zhou, and Dan Xie Copyright © 2013 Jianye Liu et al. All rights reserved. Hyperthermia as Adjunct to Intravesical Chemotherapy for Bladder Cancer Sun, 01 Sep 2013 10:47:20 +0000 http://www.hindawi.com/journals/bmri/2013/262313/ Nonmuscle invasive bladder cancer remains a very costly cancer to manage because of high recurrence rates requiring long-term surveillance and treatment. Emerging evidence suggests that adjunct and concurrent use of hyperthermia with intravesical chemotherapy after transurethral resection of bladder tumor further reduces recurrence risk and progression to advanced disease. Hyperthermia has both direct and immune-mediated cytotoxic effect on tumor cells including tumor growth arrest and activation of antitumor immune system cells and pathways. Concurrent heat application also acts as a sensitizer to intravesical chemotherapy agents. As such the ability to deliver hyperthermia to the focus of tumor while minimizing damage to surrounding benign tissue is of utmost importance to optimize the benefit of hyperthermia treatment. Existing chemohyperthermia devices that allow for more localized heat delivery continue to pave the way in this effort. Current investigational methods involving heat-activated drug delivery selectively to tumor cells using temperature-sensitive liposomes also offer promising ways to improve chemohyperthermia efficacy in bladder cancer while minimizing toxicity to benign tissue. This will hopefully allow more widespread use of chemohyperthermia to all bladder cancer patients, including metastatic bladder cancer. Richmond A. Owusu, Michael R. Abern, and Brant A. Inman Copyright © 2013 Richmond A. Owusu et al. All rights reserved. A Novel Technique of Ultra-Mini-Percutaneous Nephrolithotomy: Introduction and an Initial Experience for Treatment of Upper Urinary Calculi Less Than 2 cm Wed, 24 Jul 2013 11:35:10 +0000 http://www.hindawi.com/journals/bmri/2013/490793/ Objectives. To describe our novel modified technique of ultra-mini-percutaneous nephrolithotomy (UMP) using of a novel 6 Fr mininephroscope through an 11–13 Fr metal sheath to perform holmium: YAG laser lithotripsy. Methods. The medical records of 36 patients with moderate-sized (<20 mm) kidney stones treated with UMP from April to July 2012 were retrospectively reviewed. Patients were assessed at the 1st day and 1st month postoperatively by KUB and US to assess stone-free status. Results. The mean stone size was 14.9 ± 4.1 mm (rang: 6–20). The average operative time was 59.8 ± 15.9 (30–90) min. The stone-free rate at postoperative 1st day and 1st month was 88.9% and 97.2%. The mean hospital stay was 3.0 ± 0.9 (2–5) days. Complications were noted in 6 (16.7%) cases according to the Clavien classification, including sepsis in 2 (5.6%) cases (grade II), urinary extravasations in 1 (2.8%) case (grade IIIa), and fever in 3 (8.3%) cases (grade II). No patients needed blood transfusion. Conclusions. UMP is technically feasible, safe, and efficacious for moderate-sized renal stones with an advantage of high stone-free rates and low complication rates. However, due to the limits of its current unexplored indications, UMP is therefore a supplement to, not a substitute for, the standard mini-PCNL technology. Janak Desai, Guohua Zeng, Zhijian Zhao, Wen Zhong, Wenzhong Chen, and Wenqi Wu Copyright © 2013 Janak Desai et al. All rights reserved. Sperm Impairment by Sperm Agglutinating Factor Isolated from Escherichia coli: Receptor Specific Interactions Wed, 17 Jul 2013 12:51:46 +0000 http://www.hindawi.com/journals/bmri/2013/548497/ In an earlier work done in our laboratory, we have been able to isolate a sperm agglutinating strain of Escherichia coli from the semen sample of a male attending infertility clinic. Further, factor responsible for sperm agglutination (SAF) was isolated and purified, and, using SAF as a tool, corresponding SAF binding receptor from human spermatozoa has been purified. Characterization of SAF and SAF binding receptor using MALDI-TOF showed homology to glutamate decarboxylase and MHC class I molecule, respectively. Coincubation of SAF with spermatozoa not only resulted in spermagglutination but could also compromise other sperm parameters, namely, Mg2+ dependent ATPase activity and apoptosis. Intravaginal administration of SAF could lead to infertility in Balb/c mice. SAF induced impairment of sperm parameters, and infertility was observed to be due to interaction of SAF with sperm surface receptor component as, when purified receptor was introduced, receptor completely inhibited all the detrimental effects induced by SAF. From these results, it could be concluded that interaction of SAF with spermatozoa is receptor mediated. Kiranjeet Kaur and Vijay Prabha Copyright © 2013 Kiranjeet Kaur and Vijay Prabha. All rights reserved. Sexual Function in Women with Stress Urinary Incontinence Treated with the SPARC Sling System Sun, 14 Jul 2013 10:40:02 +0000 http://www.hindawi.com/journals/bmri/2013/957547/ Aim. To evaluate the impact of SPARC on female sexual function. Methods. 151 women with a mean age of and SUI had a complete urodynamic investigation and underwent SPARC operation. 98 women completed the validated female sexual function index questionnaire (FSFI) at baseline and 94 women at follow-up. A minimum follow-up of 12 months was required for study inclusion. Results. 52/98 women were sexually active at baseline. Postoperatively only 33 patients were sexually active. The FSFI score of all 33 pre- and postoperative sexually active women increased from at baseline to at follow-up (). Scores of women with reduced sexual function at baseline increased significantly in the domains desire, arousal, and lubrication as well as orgasm and satisfaction and total FSFI-score () postoperatively. Conclusions. Our results suggest that the SPARC-sling procedure for SUI did not negatively interfere with female sexual function. Badereddin Mohamad Al-Ali, Rany Shamloul, Georg C. Hutterer, Erika Puchwein, Karl Pummer, Alexander Avian, and Günter Primus Copyright © 2013 Badereddin Mohamad Al-Ali et al. All rights reserved. Near-Infrared Spectroscopy of the Urinary Bladder during Voiding in Men with Lower Urinary Tract Symptoms: A Preliminary Study Sun, 14 Jul 2013 10:21:53 +0000 http://www.hindawi.com/journals/bmri/2013/452857/ Objectives. To determine the difference in response of NIRS of the bladder during voiding between men with and without BOO.LUTS. Methods. A prospective, case series, study included 36 men with LUTS. Patients completed the IPSS questionnaire; prostate volumes were measured sonographically. Patients underwent pressure flow study (PFS) with simultaneous NIRS of the bladder. Amplitudes of HHb, O2Hb, and were calculated at , relative to baseline. Patients were urodynamically classified as obstructed and unobstructed. Recursive partition analysis (RPA) was performed to reclassify patients using NIRS amplitudes, followed by combined data of NIRS amplitudes, prostate volume, IPSS, and to determine the best predictor(s) of BOO. Results. PFS classified 28 patients as obstructed and 8 as unobstructed. The median HHb amplitude was significantly higher in obstructed group. RPA of NIRS amplitudes correctly reclassified 89% of patients [AUC: 0.91]. RPA of the combined IPSS, prostate volume, PVR, and correctly reclassified 72% of patients [AUC: 0.84]. When NIRS amplitudes were added to this combination, RPA revealed a significantly () higher rate of correct reclassification in 89% of patients with 89.3% sensitivity and 88% specificity for obstruction [AUC: 0.96]. Conclusion. NIRS data can be of diagnostic value for BOO in men with LUTS. Fawzy F. Farag, Joseph Meletiadis, Mohamad D. Saleem, Wout F. Feitz, and John P. Heesakkers Copyright © 2013 Fawzy F. Farag et al. All rights reserved. Prevalence Rate and Risk Factors of Depression in Outpatients with Premature Ejaculation Sat, 15 Jun 2013 17:43:07 +0000 http://www.hindawi.com/journals/bmri/2013/317468/ The purpose of this study is to investigate the prevalence rate and risk factors of depression in outpatients who were diagnosed with PE. Therefore, between September 2009 and September 2011, 1801 outpatients at andrology clinics were enrolled and consented to participate in our survey by completed a verbal questionnaire. It included the following: (1) demographic data (e.g., age, body mass index), (2) PE duration, medical history, and sexual history, (3) self-estimated intravaginal ejaculatory latency times, (4) the Zung Self-rating Depression Scale (SDS), and (5) the National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and (6) the International Index of Erectile Function (IIEF-5). The results showed that a total of 1,206 patients were diagnosed with PE. The prevalence rate of depression in these PE patients was 26.78%. Depression was associated with PE duration, NIH-CPSI score, and IIEF-5 score. Risk factors for depression specifically included PE durations for 13–24, 25–60, or ≥61 months, CPSI scores of 15–30 or ≥31, and IIEF-5 scores <22. These findings suggested that several associated factors (PE duration, CPSI scores, and IIEF-5 scores) were the risk factors of depression in men with PE. Xiansheng Zhang, Jingjing Gao, Jishuang Liu, Lei Xia, Jiajia Yang, Zongyao Hao, Jun Zhou, and Chaozhao Liang Copyright © 2013 Xiansheng Zhang et al. All rights reserved. Comparison of Prostate-Specific Promoters and the Use of PSP-Driven Virotherapy for Prostate Cancer Thu, 31 Jan 2013 08:49:57 +0000 http://www.hindawi.com/journals/bmri/2013/624632/ Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer deaths in men today. Although virus-based gene therapy is a promising strategy to combat advanced prostate cancer, its current effectiveness is limited partially due to inefficient cellular transduction in vivo. To overcome this obstacle, conditional oncolytic viruses (such as conditional replication adenovirus (CRAD)) are developed to specifically target prostate without (or with minimal) systemic toxicity due to viral self-replication. In this study, we have analyzed and compared three prostate-specific promoters (PSA, probasin, and MMTV LTR) for their specificity and activity both in vitro and in vivo. Both mice model with xenograft prostate tumor model and canine model were used. The best PSP was selected to construct a prostate-specific oncolytic adenovirus (CRAD) by controlling the adenoviral E1 region. The efficacy and specificity of CRAD on prostate cancer cells were examined in cell culture and animal models. Yi Lu, Yu Zhang, Guimin Chang, and Jun Zhang Copyright © 2013 Yi Lu et al. All rights reserved. Mechanism of Growth Inhibition of Prostate Cancer Xenografts by Valproic Acid Tue, 02 Oct 2012 13:22:32 +0000 http://www.hindawi.com/journals/bmri/2012/180363/ Valproic Acid (VPA), a histone deacetylase inhibitor, has been demonstrated to cause a marked decrease in proliferation of prostate cancer (PCa) cells in vitro and a significant reduction in tumor volume in vivo. The goal of this study is to better understand the VPA-induced growth inhibition in vivo, by studying expression of various markers in PCa xenografts. Methods. For in vitro experiments, PCa cells were treated with 0, 0.6, and 1.2 mM VPA for 14 days. For in vivo models, experimental animals received 0.4% VPA in drinking water for 35 days. Tissue microarray was generated using cell pellets and excised xenografts. Results. VPA treatment causes cell cycle arrest in PCa cells in vivo, as determined by increase in p21 and p27 and decrease in cyclin D1 expression. Increased expression of cytokeratin18 was also seen in xenografts. LNCaP xenografts in treated animals had reduced androgen receptor (AR) expression. While decreased proliferation was found in vitro, increase in apoptosis was found to be the reason for decreased tumor growth in vivo. Also, an anti-angiogenic effect was observed after VPA treatment. Conclusion. VPA inhibits tumor growth by multiple mechanisms including cell cycle arrest, induction of differentiation, and inhibition of growth of tumor vasculature. Abhinav Sidana, Muwen Wang, Shabana Shabbeer, Wasim H. Chowdhury, George Netto, Shawn E. Lupold, Michael Carducci, and Ronald Rodriguez Copyright © 2012 Abhinav Sidana et al. All rights reserved. No Evidence for Statin-induced Proteinuria in Healthy Volunteers as Assessed by Proteomic Analysis Tue, 13 Sep 2011 10:32:45 +0000 http://www.hindawi.com/journals/bmri/2011/456076/ In clinical studies of statins (class of drugs lowering plasma cholesterol levels), transient low-molecular-weight proteinuria was observed. The causes of statin-induced proteinuria in the patient background of those studies (cardiovascular and kidney disease) are multifactorial and, therefore, a matter of debate. In light of this, it seemed interesting to investigate the effect of statins on the urinary protein concentration and proteome in healthy volunteers. Six healthy volunteers were randomly treated with rosuvastatin (40 mg/day) or pravastatin (80 mg/day) in a double-blinded cross-over study. Total urinary protein concentration and the concentration of albumin/retinol-binding protein were analysed, after which the urinary proteome was investigated. From the results described in this study, it was concluded that statins do not induce major changes in the urinary protein concentration/proteome. High variability in the baseline urinary proteome/proteins among volunteers, however, made it very difficult to find subtle (possibly isolated to individuals) effects of statins. Anja Verhulst, Hilde Geryl, and Patrick D'Haese Copyright © 2011 Anja Verhulst et al. All rights reserved. A Metabonomic Comparison of Urinary Changes in Zucker and GK Rats Wed, 13 Oct 2010 13:20:41 +0000 http://www.hindawi.com/journals/bmri/2010/431894/ To further investigate pathogenesis and pathogenic process of type 2 diabetes mellitus (T2DM), we compared the urinary metabolic profiling of Zucker obese and Goto-kakizaki (GK) rats by NMR-based metabonomics. Principal component analysis (PCA) on urine samples of both models rats indicates markedly elevated levels of creatine/creatinine, dimethylamine, and acetoacetate, with concomitantly declined levels of citrate, 2-ketoglurarate, lactate, hippurate, and succinate compared with control rats, respectively. Simultaneously, compared with Zucker obese rats, the GK rats show decreased levels of trimethylamine, acetate, and choline, as well as increased levels of creatine/creatinine, acetoacetate, alanine, citrate, 2-ketoglutarate, succinate, lactate, and hippurate. This study demonstrates metabolic similarities between the two stages of T2DM, including reduced tricarboxylic acid (TCA) cycle and increased ketone bodies production. In addition, compared with Zucker obese rats, the GK rats have enhanced concentration of energy metabolites, which indicates energy metabolic changes produced in hyperglycemia stage more than in insulin resistance stage. Liang-Cai Zhao, Xiao-Dong Zhang, Shi-Xian Liao, Hong-Chang Gao, He-Yao Wang, and Dong-Hai Lin Copyright © 2010 Liang-Cai Zhao et al. All rights reserved. The Immunoexpression of FSH-R in the Ductuli Efferentes and the Epididymis of Men and Rat: Effect of FSH on the Morphology and Steroidogenic Activity of Rat Epididymal Epithelial Cells In Vitro Wed, 12 May 2010 11:09:03 +0000 http://www.hindawi.com/journals/bmri/2010/506762/ The Sertoli cells were regarded as the only target for FSH in male reproductive system. The expression of FSH receptor (FSH-R) was detected also in epithelial cells of the caput epididymis of rat and monkey. We showed in the immunohistochemistry study the expression of FSH-R in rat and human ductuli efferentes and the caput, corpus, and cauda epididymis, moreover, by Western blot analysis in the caput and cauda epididymis of rat. Additionally, we presented that the morphology of rat epididymal epithelial cells in vitro was affected by FSH, and FSH stimulation resulted in the increase of 17𝛽-estradiol synthesis by rat caput epididymal cells in dose-depended manner. In conclusion, the identification of FSH receptors in human and rat epididymides supports our results that the epididymis is a target organ not only for LH but additionally for FSH. On the basis of the results we showed for the first time that morphology of epididymal epithelial cells and epididymal steroidogenesis can be regulated by FSH. Małgorzata Świder-Al-Amawi, Agnieszka Kolasa, Andrzej Sikorski, Mariola Marchlewicz, Irena Baranowska-Bosiacka, and Barbara Wiszniewska Copyright © 2010 Małgorzata Świder-Al-Amawi et al. All rights reserved.