Romel Wazir

Effects of circumcision on male sexual functions: a systematic review and meta-analysis

This meta-analysis was performed to assess sexual functions following adult male circumcision. We searched the Cochrane Central Register of Controlled Trials, PUBMED, EMBASE, the Cochrane Database of Systematic Review and Web of Science from their inception until January 2013 to identify all eligible studies that reported on mens sexual function after circumcision. The Cochrane Collaborations RevMan 5.2 software was employed for data analysis, and the fixed or the random effect model was selected depending on the proportion of heterogeneity. We identified 10 studies, which described a total of 9317 circumcised and 9423 uncircumcised men who were evaluated for the association of circumcision with male sexual function. There were no significant differences in sexual desire (odds ratio (OR): 0.99; 95% confidence interval (CI): 0.92-1.06), dyspareunia (OR: 1.12; 95% CI: 0.52-2.44), premature ejaculation (OR: 1.13; 95% CI: 0.83-1.54), ejaculation latency time (OR: 1.33; 95% CI: 0.69-1.97), erectile dysfunctions (OR: 0.90; 95% CI: 0.65-1.25) and orgasm difficulties (OR: 0.97; 95% CI: 0.83-1.13). These findings suggest that circumcision is unlikely to adversely affect male sexual functions. However, these results should be evaluated in light of the low quality of the existing evidence and the significant heterogeneity across the various studies. Well-designed and prospective studies are required for a further understanding of this topic.

Integrin αv Mediates Contractility Whereas Integrin α4 Regulates Proliferation of Human Bladder Smooth Muscle Cells via FAK Pathway under Physiological Stretch

PURPOSE The requirement of integrins for mechanotransduction has been recognized for some time. We investigated the role of integrin subunits and their pathway in the physiological stretch induced contractility and proliferation of human bladder smooth muscle cells. MATERIALS AND METHODS Human bladder smooth muscle cells were seeded on silicone membrane and subjected to stretch, simulating bladder cycles of various stretches and times, as controlled by customized software on a modified BioDynamic bioreactor. Cell proliferation, viability and cycle were determined by BrdU incorporation assay, the Cell Counting Kit-8 (Beyotime Institute of Biotechnology, Haimen, Peoples Republic of China) and flow cytometry, respectively. Cell contractility was determined using a collagen gel contraction assay. RESULTS Physiological stretch increased cell contractility, proliferation and viability. Knockdown of integrin αv but not α4 in the cells disrupted the enhanced contractility induced by stretch. Under physiological stretch conditions, the integrin αv level and phospho-FAK/FAK ratio correlated positively with cell stretch induced enhanced contractility. Further examination revealed that contractile marker expression was associated with integrin αv activation through the FAK pathway. At the same time integrin α4 but not integrin αv mediated stretch induced cell proliferation and viability. CONCLUSIONS These data revealed that different integrins have different roles in the contractility and proliferation of human bladder smooth muscle cells under physiological stretch. This suggests that different integrins may become specific therapeutic targets in patients with voiding dysfunction. They may also be used to design a specific microenvironment for optimal bladder tissue regeneration.

Expression and proliferation profiles of PKC, JNK and p38MAPK in physiologically stretched human bladder smooth muscle cells

OBJECTIVE To determine protein kinase C (PKC), c-Jun NH2-Terminal Kinase (JNK) and P38 mitogen-activated protein kinases (p38MAPK) expression levels and effects of their respective inhibitors on proliferation of human bladder smooth muscle cells (HBSMCs) when physiologically stretched in vitro. MATERIALS AND METHODS HBSMCs were grown on silicone membrane and stretch was applied under varying conditions; (equibiaxial elongation: 2.5%, 5%, 10%, 15%, 20%, 25%), (frequency: 0.05, 0.1, 0.2, 0.5, 1Hz). Optimal physiological stretch was established by assessing proliferation with 5-Bromo-2-deoxyuridine (BrdU) assay and flow cytometry. PKC, JNK and p38 expression levels were analyzed by Western blot. Specificity was maintained by employing specific inhibitors; (GF109203X for PKC, SP600125 for JNK and SB203580 for p38MAPK), in some experiments. RESULTS Optimum proliferation was observed at 5% equibiaxial stretch (BrdU: 0.837±0.026 (control) to 1.462±0.023)%, (P<0.05) and apoptotic cell death rate decreased from 16.4±0.21% (control) to 4.5±0.13% (P<0.05) applied at 0.1Hz. Expression of PKC was upregulated with slight increase in JNK and no change in p38MAPK after application of stretch. Inhibition had effects on proliferation (1.075±0.024, P<0.05 GF109203X); (1.418±0.021, P>0.05 SP600125) and (1.461±0.01, P>0.05 SB203580). These findings show that mechanical stretch can promote magnitude-dependent proliferative modulation through PKC and possibly JNK but not via p38MAPK in hBSMCs.

Magnitude-dependent proliferation and contractility modulation of human bladder smooth muscle cells under physiological stretch

AbstractPurpose The purpose of this study was to describe and test a kind of stretch pattern which is based on modified BOSE BioDynamic system to produce optimum physiological stretch during bladder cycle. Moreover, we aimed to emphasize the effects of physiological stretch’s amplitude upon proliferation and contractility of human bladder smooth muscle cells (HBSMCs). MethodsHBSMCs were seeded onto silicone membrane and subjected to stretch simulating bladder cycle at the range of stretches and time according to customized software on modified BOSE BioDynamic bioreactor. Morphological changes were assessed using immunofluorescence and confocal laser scanning microscope. Cell proliferation and cell viability were determined by BrdU incorporation assay and Cell Counting Kit-8, respectively. Contractility of the cells was determined using collagen gel contraction assay. RT-PCR was used to assess phenotypic and contractility markers.ResultsHBSMCs were found to show morphologically spindle-shaped and orientation at various elongations in the modified bioreactor. Stretch-induced proliferation and viability depended on the magnitude of stretch, and stretches also regulate contractility and contraction markers in a magnitude-dependent manner.ConclusionWe described and tested a kind of stretch pattern which delivers physiological stretch implemented during bladder cycle. The findings also showed that mechanical stretch can promote magnitude-dependent morphological, proliferative and contractile modulation of HBSMCs in vitro.

Primary adenocarcinoma of the rete testis: A case report and review of the literature

Primary adenocarcinoma of the rete testis is an extremely rare extratesticular neoplasm. Due to its low occurrence and the scarcity of data, sonographic characteristics of adenocarcinoma of the rete testis are still poorly defined. A 46-year-old male complained of swelling and pain in the right side of the scrotum. No associated symptoms were observed. Anti-tuberculosis chemotherapy yielded no response. Postoperative pathology revealed a diagnosis of poorly-differentiated adenocarcinoma of the rete testis. Using the ultrasonography features observed, combined with a review of current literature, the diagnosis and differential diagnosis of this neoplasm are presented.

The purinergic component of human bladder smooth muscle cells' proliferation and contraction under physiological stretch

OBJECTIVE To investigate whether cyclic stretch induces proliferation and contraction of human smooth muscle cells (HBSMCs), mediated by P2X purinoceptor 1 and 2 and the signal transduction mechanisms of this process. METHODS HBSMCs were seeded on silicone membrane and stretched under varying parameters; (equibiaxial elongation: 2.5%, 5%, 10%, 15%, 20%, 25%), (Frequency: 0.05Hz, 0.1Hz, 0.2Hz, 0.5Hz, 1Hz). 5-Bromo-2-deoxyuridine assay was employed for proliferative studies. Contractility of the cells was determined using collagen gel contraction assay. After optimal physiological stretch was established; P2X1 and P2X2 were analyzed by real time polymerase chain reaction and Western Blot. Specificity of purinoceptors was maintained by employing specific inhibitors; (NF023 for P2X1, and A317491for P2X2), in some experiments. RESULTS Optimum proliferation and contractility were observed at 5% and 10% equibiaxial stretching respectively, applied at a frequency of 0.1Hz; At 5% stretch, proliferation increased from 0.837±0.026 (control) to 1.462±0.023%, p<0.05. Mean contraction at 10% stretching increased from 31.7±2.3%, (control) to 78.28 ±1.45%, p< 0.05. Expression of P2X1 and P2X2 was upregulated after application of stretch. Inhibition had effects on proliferation (1.232±0.051, p<0.05 NF023) and (1.302±0.021, p<0.05 A314791) while contractility was markedly reduced (68.24±2.31, p<0.05 NF023) and (73.2±2.87, p<0.05 A314791). These findings shows that mechanical stretch can promote magnitude-dependent proliferative and contractile modulation of HBSMCs in vitro, and P2X1 and 2 are at least partially responsible in this process.

Cyclic stretch induces human bladder smooth muscle cell proliferation in vitro through muscarinic receptors.

The present study aimed to investigate whether the cyclic stretch‑induced proliferation of human bladder smooth muscle cells (HBSMCs) is mediated by muscarinic (M) receptors, together with the signal transduction mechanisms involved in this process. HBSMCs seeded onto silicone membranes were subjected to different cyclic stretches (5, 10, 15 and 20%) for 6 and 12 h. As the effect of cyclic stretch on M2 and M3 mRNA expression levels was maximal at 6 h 10% stretch, all subsequent experiments were performed at this stretch. Western blot analysis was used to quantify M2, M3, protein kinase C (PKC) and phosphorylated (p)‑PKC protein expression levels, flow cytometry was employed to examine cell cycle distribution and a 5-bromo‑2-deoxyuridine (BrdU) incorporation assay was used to assess cell proliferation at this stretch. Subsequently, HBSMCs were exposed to different acetylcholine concentrations and/or cyclic stretch, M receptor antagonists [AF-DX16, an M2 receptor antagonist; 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide (4-DAMP), an M3 receptor antagonist and atropine, a non‑selective antagonist] and GF 109203X, a PKC antagonist, to assess the possible underlying signaling mechanisms. Cyclic stretch was found to increase the proliferation of HBSMCs and the expression levels of M2, M3, PKC and p‑PKC proteins. M receptor and PKC antagonists exerted no apparent effect on nonstretched cells, but reduced the incorporation of BrdU into stretched cells; the most pronounced effects were observed when non‑selective M receptor and PKC antagonists were applied. Notably, 4‑DAMP did not inhibit stretch‑induced PKC activation. These results indicate that the activation of the M3 receptor signaling pathway in stretch‑induced HBSMC proliferation occurs via PKC-independent mechanisms.

Male circumcision decreases penile sensitivity as measured in a large cohort

We read the article by Hocaoglu et al. [1] with great interest and are grateful to authors for providing us with the detailed anatomical changes, biometric and functional analysis of the prostate during micturition. The authors suggested that the process of micturition initiates with relaxation of the pelvic floor and descent of the external sphincter followed by funnelling of the bladder neck and contraction of the ventral prostate. The detrusor muscle orients into three distinct layers at the level of the bladder neck; the inner and outer longitudinal fibres extend into the urethra. During bladder emptying these longitudinal layers contract thus pulling the bladder neck open. These muscle fibres mix with the prostatic stroma. The authors mention that the anterior/ventral prostate contracts during micturition. We feel that this observation could be the same phenomenon that occurs due to the contraction of the longitudinal bladder muscles. The posterior prostate of elderly patients develops hyperplasia of glands and therefore the contraction is not noticed.