This Month in Investigative Urology

Article Outline

• Cellular Telephone Radio Frequency Exposure and Testicular Function
• Effect of On-Demand Dapoxetine on Premature Ejaculation
• Relationship of Biofilm Formation with Prostatitis
• Androgen and Success of Cavernous Nerve Grafting
• α-1L and α-1A Adrenoceptors in the Prostate
• Copyright

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Cellular Telephone Radio Frequency Exposure and Testicular Function 

Widespread cellular telephone use has led to a growing public concern over the possible health risks of human exposure to the low intensity radio frequency and microwave energies that cellular telephones emit. Although it is nonionizing radiation, radio frequency is capable of causing biological effects by thermal and nonthermal mechanisms. While it is well established that the heating effects may cause health injury (eg severe damage to spermatogenesis), the link between the direct interaction of nonionizing radiation with biological tissues by nonthermal effects and health hazard is much weaker.

Ribeiro et al (page 395) from Porto Alegre, Brazil evaluated the effects of subchronic exposure to radio frequency emitted from a conventional cellular telephone on testicular function in adult rats. Wistar rats were randomly divided into experimental and control groups. The experimental group was exposed to radio frequency emitted from a conventional GSM (global system for mobile communications) cellular telephone (1,835 to 1,850 MHz), for 1 hour daily during 11 weeks. Rectal temperature was measured before and after exposure. Testicular and epididymal weight, lipid peroxidation levels in these organs, serum total testosterone levels and epididymal sperm count were evaluated. Maturation phase spermatid retention, cellular vacuolation and multinucleate giant cells were among the qualitative testicular histopathological end points analyzed. There was no statistical difference between control and experimental groups in any end points evaluated. This study showed that low intensity pulsed radio frequency emitted by a conventional cellular telephone does not impair testicular function in adult rats.

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Effect of On-Demand Dapoxetine on Premature Ejaculation 

During the last decade clinical evidence has emerged indicating a beneficial effect of selective serotonin reuptake inhibitors for the treatment of men with premature ejaculation. Of all selective serotonin reuptake inhibitors tested to date in clinical trials, paroxetine administered on a chronic, daily basis appeared to be the most efficient method for treating premature ejaculation. Whereas there is no doubt that daily administration of selective serotonin reuptake inhibitors provides benefit to men with premature ejaculation, there are conflicting results regarding the clinical relevance of on-demand regimens. Giuliano et al (page 386) from Garches, France investigated the effect of acute intravenous delivery of dapoxetine in anesthetized rats.

Dapoxetine is the first short-acting selective serotonin reuptake inhibitor, which is currently in the later phases of clinical development for on-demand treatment of premature ejaculation. The investigators used a previously described experimental model of the expulsion reflex, that is pudendal motoneuron reflex discharges elicited by electrical stimulation of dorsal nerves of the penis, which convey sensory afferents from the glans to the spinal cord. The effect of acute dapoxetine was compared with that of acute paroxetine, which was used as the selective serotonin reuptake inhibitor of reference. Stimulating electrodes were placed bilaterally on the dorsal nerves of the penis and a recording electrode was placed on the motor branch of the pudendal nerve to monitor pudendal motoneuron reflex discharges in anesthetized rats. Pudendal motoneuron reflex discharges induced by penile dorsal nerve stimulation were measured before and 60 minutes after a single intravenous injection of dapoxetine or paroxetine, each tested at 3 doses or after a single injection of vehicle. At all doses tested dapoxetine significantly lengthened the latency of pudendal motoneuron reflex discharges following bilateral stimulation of the dorsal nerves of the penis in comparison with vehicle. The study showed that acute intravenous administration of dapoxetine was capable of modulating the expulsion reflex loop. This provides experimental evidence of the mechanism by which selective serotonin reuptake inhibitors may delay ejaculation in copulating rats. The results support the demonstrated efficacy of oral on-demand administration of dapoxetine for delaying ejaculation in patients with premature ejaculation.

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Relationship of Biofilm Formation with Prostatitis 

Biofilms are defined as structured bacterial communities embedded in a self-produced exopolysaccharide matrix adherent to any abiotic or biological surface. Biofilm formation may be considered an important pathogenic determinant which allows bacterial strains to persist a long time in the genitourinary tract and interfere with bacterial eradication. Soto et al (page 365) from Barcelona, Spain determined the capacity of clinical Escherichia coli strains to form biofilm structures in patients with urinary tract infections, and determined the possible relationship among in vitro biofilm formation, the presence of urovirulence factors and nalidixic acid resistance. A total of 151 E. coli strains collected from patients with cystitis, pyelonephritis and prostatitis were analyzed. E. coli strains causing prostatitis produced biofilm in vitro more frequently than those causing other urinary tract infections and had a higher frequency of hemolysin. Strains forming biofilm presented a significantly higher frequency of hemolysin and type 1 fimbriae expression. The study showed that biofilm production is one of the several putative virulence determinants possessed by uropathogenic E. coli causing acute prostatitis, and that it is associated with hemolysin and type 1 fimbriae expression. Even if not directly involved in invasiveness (a property apparently linked to hemolysis), biofilm formation may still result in the increased ability of strains causing acute prostatitis to persist in the prostatic secretory system and lead to the recurrent urinary tract infections characteristic of chronic bacterial prostatitis.

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Androgen and Success of Cavernous Nerve Grafting 

Iatrogenic erectile dysfunction following radical prostatectomy is primarily neurogenic in origin. Attempts to improve postoperative potency aim to preserve or regenerate the autonomic cavernous nerves. Testosterone is integral for erectile function and has profound positive effects on nerve regeneration. Androgen ablation impairs nerve regeneration. Syme et al (page 390) from Melbourne, Australia evaluated whether testosterone deprivation effects axonal regeneration in cavernous nerve grafts or the erectile response to cavernous nerve graft stimulation. Sprague-Dawley rats underwent bilateral cavernous nerve neurotomy followed by unilateral nerve graft using the genitofemoral nerve. Rats were then randomized to castrate, intact and testosterone treated arms. At 3 months grafts were explored and electrostimulation was performed with intracavernous pressure responses recorded. Grafted nerves were then harvested for immunohistochemical analysis. Functional outcomes in castrate (androgen ablated) animals did not return to those in intact animals with androgen replacement before assessment. This appears to be due to a reduced number of neuronal nitric oxide synthase positive axons regenerating through the nerve graft segment. Whether a longer period of androgen replacement before evaluation would create a different effect is uncertain. While experimental models offer only a guide to outcomes in humans, this study suggests that structural and functional outcomes following cavernous nerve grafting in patients who receive androgen ablation therapy would be inferior to those in patients not receiving androgen ablation therapy. Therefore, the future androgen status of a patient should be considered when cavernous nerve grafts might be used in an attempt to maximize erectile function outcomes postoperatively. Further studies to more definitively assess clinical relevance in humans are indicated.

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α-1L and α-1A Adrenoceptors in the Prostate 

Bladder outlet obstruction due to benign prostatic hyperplasia is attributable to a mechanical and a dynamic component. The dynamic component is related to the contraction of smooth muscle in the prostate, for which α-1 adrenoceptor is considered to be of primary functional importance. Three α-1 adrenoceptor subtypes (α-1A, 1B and 1D) have now been cloned and identified pharmacologically as sites showing high (subnanomolar) affinity for the classic α-1 adrenoceptor antagonist prazosin. Expression of these 3 subtypes has been detected at the mRNA level in the human prostate, but there is a controversy about which functional receptor subtype has the primary role in prostate smooth muscle contraction. Many groups think that an additional α-1A adrenoceptor subtype (putative α-1L adrenoceptor) has a role in prostate contraction, which shows different pharmacological profiles than those of cloned α-1 adrenoceptor subtypes. To characterize the pharmacological profiles of receptors according to radioligand binding criteria, most studies have so far used tissue derived microsomal membrane preparations. However, it has been pointed out that tissue homogenization may cause dramatic changes in the membrane receptor environment, possibly leading to changes in its pharmacological profile. Morishima et al (page 377) from Fukui, Japan reevaluated functional α-1 adrenoceptors in human prostate compared with binding data on intact tissue segments and homogenates. To detect α-1L adrenoceptors more selectively without α-1B and α-1D subtype contamination the investigators used [³H]-silodosin (selective for α-1A and α-1L adrenoceptors) as a radioligand probe in binding experiments, and the binding affinities for various drugs were estimated. In functional experiments antagonist affinities were evaluated from the inhibitory potency against the contractile response to noradrenaline. The binding studies with human prostate samples clearly showed that α-1L and α-1A adrenoceptors coexist as pharmacologically distinct entities in intact tissues but not in crude membrane preparations, and that the α-1 adrenoceptors involved in the contractile response to noradrenaline are the α-1L subtype. These findings may be significant for the use of novel therapeutic agents for benign prostatic hyperplasia.