This Month in Investigative Urology

Article Outline

• Enhancement of Human Sperm Motility by Trophinin Binding Peptide May Avert the Need for Intracytoplasmic Sperm Injection
• Use of Cyanoacryclic Glue on Penile Fractures
• Intraprostatic Botulinum Toxin A Injection Suppresses Prostatic Pain
• Fatty Acid Synthase Inhibitors Suppress Renal Cancer Cell Growth
• The Role of Epithelial-Mesenchymal Transition in Obstructive Nephropathy
• Copyright

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Enhancement of Human Sperm Motility by Trophinin Binding Peptide May Avert the Need for Intracytoplasmic Sperm Injection 

Trophinin is an integral membrane protein with its N-terminal region in the cytoplasm and unique decapeptide repeats on the cell surface. The evolutionarily conserved cytoplasmic protein bystin binds to the trophinin cytoplasmic domain. Bystin also binds to the proline rich, microtubule associated protein tastin, and tastin binds to Tctex-1, the light chain of the microtubule associated adenosine triphosphatase (ATPase) dynein. When dynein ATPase is activated by phosphorylation, sperm tails beat as adenosine triphosphate hydrolysis is converted to force, causing microtubules to slide against each other. Hatakeyama et al (page 767) from La Jolla, California suggest that trophinin has a role in regulating sperm motility by arresting ATPase in normal human sperm. The trophinin binding peptide GWRQ activates human trophoblastic cells. Although trophinin is expressed in human sperm the function of this protein in not known. The presence of trophinin and the trophinin associated proteins bystin and tastin in human sperm was confirmed by immunohistochemistry. The multivalent 8-branched GWRQ peptide (GWRQ-MAPS) was chemically synthesized. Sperm cells incubated with GQRQ-MAPS showed reduced adenosine triphosphate levels and increased levels of intracellular calcium, suggesting that trophinin has a role in regulating ATPase in human sperm.

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Use of Cyanoacryclic Glue on Penile Fractures 

Penile fracture is defined as rupture of the corpus cavernosum due to blunt trauma to the erect penis. Immediate surgical intervention is often recommended to preserve the tunical integrity that is essential for erection. Cyanoacrylates were first described in 1949 and their potential as adhesives was quickly recognized. Akgül et al (page 749) from Ankara, Turkey investigated the effects of a glue composed of N-butyl-2-cyanoacrylate and methacryloxysulfolane on penile cavernous tissue of experimentally created penile fractures. Experimental penile fractures were formed by incising the proximal dorsal side of the penis in Wistar Albino rats that were randomly assigned to 4 groups. When the experimental groups were evaluated for histopathological parameters the best results were obtained when the glue was only applied on the incision. The combination glue used in this study may be used in cavernous surgery due to its hemostatic, adhesive and anti-inflammatory properties. The application of the material on the ruptured region of the corpus cavernosum without suturing may be clinically beneficial.

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Intraprostatic Botulinum Toxin A Injection Suppresses Prostatic Pain 

Prostatitis can exist due to bacterial infection but more commonly nonbacterial prostatitis accounts for more than 90% of all cases. A possible cause of type III nonbacterial prostatitis may be neurogenic inflammation, which activates prostate afferent nerves, and provokes prostate inflammation, prostatic pain and referred pain. Botulinum toxin A (BoNT-A) is well-known for its ability to block acetylcholine release at neuromuscular junctions and it may have therapeutic effects on muscular hypercontraction. Cyclooxygenase (COX)-2 is a key enzyme in the conversion of arachidonic acid to prostaglandins, which are important mediators of inflammation and pain. Chuang et al (page 742) from Pittsburgh, Pennsylvania investigated the effect of intraprostatic BoNT-A administration on pain reaction and COX-2 expression in a capsaicin induced prostatitis model in rats. Adult male rats were injected with vehicle or capsaicin into the prostate. A second set of animals was injected with BoNT-A into the prostate 1 week before intraprostatic injection of capsaicin. Intraprostatic capsaicin injection activates COX-2 expression in the prostate, and spinal sensory and motor neurons, and induces prostatic pain. BoNT-A pretreatment could inhibit capsaicin induced COX-2 expression from the peripheral organ to the L6 spinal cord, and inhibit prostatic pain and inflammation. This finding suggests a potential clinical benefit of BoNT-A for the treatment of nonbacterial prostatitis.

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Fatty Acid Synthase Inhibitors Suppress Renal Cancer Cell Growth 

Fatty acids, which have an essential role in a variety of cellular processes, are obtained from the diet or synthesized from carbohydrate precursors. Fatty acid synthase (FAS) synthesizes long chain fatty acids using acetyl-coenzyme A as a primer, malonyl-coenzyme A as a 2-carbon donor and NADPH (reduced nicotinamide adenine dinucleotide phosphate) as a reducing equivalent. Most normal human tissues other than those in the lactating breast and cycling endometrium acquire most of the fatty acids they require from the circulation, so that de novo lipogenesis and expression of FAS are low. However, it has been suggested that FAS is up-regulated in a wide range of cancers and it has emerged as an effective drug target for treatment. Consistent with this idea the pharmacological FAS inhibitors cerulenin and C75 have been shown to induce cell death in many tumor cell lines. Cerulenin was the first specific inhibitor of FAS to be identified, while C75 is a more potent and more stable derivative that provided the initial in vivo evidence for reduced tumor growth following FAS inhibition. Horiguchi et al (page 729) from Saitama, Japan examined whether FAS could be a novel therapeutic target for renal cell carcinoma using the pharmacological FAS inhibitor C75. All renal cancer cell lines expressed detectable FAS, and C75 significantly inhibited cell viability and growth by arresting the cell cycle and inducing apoptosis. The covered area in the wound and the number of cells invading through a Matrigel™ chamber were significantly smaller for cells treated with C75 than they were for control cells treated with vehicle. C75 suppressed Her2 and epidermal growth factor receptor expression as well as STAT3 phosphorylation while increasing p53 and p21 expression. Intraperitoneal administration of C75 significantly decreases the tumor volume of renal cancer xenografts. Pharmacological inhibition of FAS could be an effective strategy for treating renal cell carcinoma.

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The Role of Epithelial-Mesenchymal Transition in Obstructive Nephropathy 

Tubulointerstitial fibrosis is the final common pathway to end stage renal disease. The pathophysiology of renal fibrosis involves fibroblast proliferation, macrophage infiltration, the elaboration of cytokines and other proinflammatory mediators, and an imbalance in extracellular matrix deposition and degradation. Although the exact origin of activated fibroblasts remains uncertain, emerging evidence indicates that mature tubular epithelial cells are capable of transforming into myofibroblasts under pathological conditions, a process that is called epithelial-mesenchymal transition. Bani-Hani et al (page 461) from Indianapolis, Indiana present a comprehensive review of how epithelial-mesenchymal transition is believed to have a role in obstructive nephropathy. Epithelial-mesenchymal transition is an orchestrated, highly regulated process that proceeds in stepwise fashion, and appears to contribute significantly to renal fibrosis and the progression of chronic renal disease. Recent insights into the molecular events and intrinsic signaling pathways that are active during epithelial-mesenchymal transition have evoked novel therapeutic strategies aimed at halting the onset and progression of chronic renal fibrosis.