BioMed Research International: Urology http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . 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. 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. 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. 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.