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CGRP immunoreactivity and NADPH-diaphorase in afferent nerves of the rat penis.

Calcitonin gene-related peptide (CGRP)-immunoreactive afferent nerve fibers are abundant in the rat penis. In addition, NADPH-diaphorase, which stains for nitric oxide synthase, has been localized within both autonomic and sensory dorsal root ganglia (DRG) and may be part of an important biochemical pathway involved in penile tumescence. The purpose of this study was: 1) to examine the circuitry of afferent nerves that are CGRP immunoreactive from the L6 DRG, 2) to examine the possibility that there are NADPH-diaphorase-positive afferent fibers from the L6 DRG to the rat penis, and 3) to examine the localization and colocalization of CGRP and NADPH-diaphorase within L6 DRG afferent perikarya. Calcitonin gene-related peptide immunostaining in the penis was eliminated following a bilateral transection of the pudendal nerves, but was unchanged following a bilateral transection of the pelvic splanchnic or hypogastric nerves. The NADPH-diaphorase staining was not altered by any of the nerve transections. Injection of the retrograde axonal tracer fluorogold (FG) into the dorsum penis labeled perikarya in the L6 DRG. Although the majority of FG-labeled perikarya contained neither CGRP nor NADPH-diaphorase, small subpopulations of perikarya contained either CGRP immunoreactivity, NADPH-diaphorase, or both. A unilateral pudendal nerve transection virtually eliminated (> 99%) FG labeling in the ipsilateral L6 DRG. These data suggest that NADPH-diaphorase and CGRP are present, either together or separately, within a subpopulation of penile afferent perikarya. In addition, CGRP-immunoreactive afferent nerve fibers reach the penis primarily via the pudendal nerves. Finally, NADPH-diaphorase-positive penile afferents may be another important source of nitric oxide (NO) for penile tumescence.

Afferent Pathways↗

Reconstruction of the penis after severe injury.

Since 1986, five cases of one-stage reconstruction of the injured penis using microsurgical techniques have been successfully carried out. A piece of ilium based upon the deep circumflex iliac vessels is used to form the penis prop and a skin flap of the forearm is transferred to form the urethra and foreskin to encircle the prop. Then the vessels and nerves of the skin flap of the forearm are anastomosed with the vessels and nerves of the thigh. Postoperative follow-up showed the constructed penis to be satisfactory in contour, allow free flow of urine, provide cutaneous sensory recovery and satisfactory sexual function in four married patients. Radiography showed the bony structure of the penis prop to be normal. This method has advantages over the one-stage procedure in terms of contour, urinary flow, satisfactory sexual function and long-term benefits. Most of all it has solved the problem of poor blood supply into the reconstructed penis prop.

Adult↗

Importance of identifying the inconspicuous penis: prevention of circumcision complications.

OBJECTIVES: To report the incidence of inconspicuous penis in those referred to a pediatric urologist for circumcision or revision of circumcision. METHODS: We performed a chart review of 129 boys referred to one pediatric urologist during a 3-year period for circumcision. RESULTS: Of 129 patients, 30 (23%) had evidence of an inconspicuous penis on the physical examination. Eight (9%) of 94 patients referred for the initial circumcision and 22 (63%) of 35 patients referred for a circumcision revision had evidence of an inconspicuous penis on physical examination. CONCLUSIONS: Inconspicuous penis is an umbrella term used to categorize several anatomic anomalies that occur in newborn boys. The incidence of inconspicuous penis at physical examination in children referred for circumcision revision is remarkable. Circumcision is best delayed in these newborn patients until a later time.

Adolescent↗

Metastasis to the penis in a patient with squamous cell carcinoma of the lung with a review of reported cases.

Metastasis to the penis is very rare in lung cancer. We describe a patient with squamous cell carcinoma of the lung who developed a metastatic lesion in the penis. A 75-year-old Japanese male visited a local hospital complaining cough and bloody sputum. A chest plain radiograph and computed tomographic (CT) scans of the chest demonstrated a right hilar mass. He was diagnosed with squamous cell carcinoma of the lung at stage IIIB (T4N2M0). Then he was treated with concurrent chemoradiotherapy consisting of cisplatin, docetaxel, and thoracic irradiation, and after the chemoradiotherapy, he achieved a partial response. However, 6 months later, he visited an urologist complaining of firm mass in the penis with slight pain. A biopsy of the corpus cavernosum penis was performed, which provided a histological diagnosis of squamous cell carcinoma. The histology of the specimen was consistent with that of previous lung cancer, so he was considered to have penile metastasis from squamous cell carcinoma of the lung. Radiotherapy was given to the metastatic tumor in the penis. The penile tumor was diminished and the pain was completely relieved. In addition, we review reported cases to investigate the clinical characteristics and appropriate management of this rare involvement.

Aged↗

Neuronal and endothelial nitric oxide synthase isoforms: quantification of protein and mRNA in the normal rat penis.

Nitric oxide synthase (NOS) is an important enzyme for erection. We evaluated the content of neuronal (nNOS) and endothelial (eNOS) isoforms and their mRNA in the penis and major pelvic ganglion (MPG) of adult male rats by Western and Northern blot analysis. The cerebellum was evaluated as a control. nNOS protein and its mRNA were detected in abundance in the MPG, cerebellum, pelvic urethra and within the crura of the penis. In contrast, the penile urethra, neurovascular bundle and the shaft of penis contained smaller amounts of this protein. eNOS protein was most abundant in the penile and pelvic parts of the urethra, whereas a moderate level was found in the penile shaft, crura, neurovascular bundle, MPG and cerebellum. Similarly eNOS mRNA was abundant in the penile and pelvic parts of the urethra, MPG and cerebellum. Penile shaft, crura and neurovascular bundle showed moderate amounts of eNOS mRNA. In conclusion, nNOS and its mRNA are most abundant in the MPG and crura of penis whereas eNOS is most abundant in the urethra and to a lesser extent present in the penis. Importantly eNOS protein and mRNA were demonstrated in the MPG, where eNOS function has to be studied.

Animals↗

Human glans penis augmentation using injectable hyaluronic acid gel.

Although augmentation phalloplasty is not an established procedure, some patients still need enlargement of their penis. Current penile augmentation is girth enhancement of penile body by dermofat graft. We performed this study to identify the efficacy and the patient's satisfaction of human glans penis augmentation with injectable hyaluronic acid gel. In 100 patients of subjective small penis (Group I) and 87 patients of small glans after dermofat graft (Group II), 2 cm(3) of hyaluronic acid gel was injected into the glans penis, subcutaneously. At 1 y after injection, changes of glandular diameter were measured by tapeline. Patient's visual estimation of glandular size (Gr 0-4) and patient's satisfaction (Grade (Gr) 0-4) were evaluated, respectively. Any adverse reactions were also evaluated. The mean age of patients was 42.2 (30-70) y in Group I and 42.13 (28-61) y in Group II. The maximal glandular circumference was significantly increased compared to basal circumference of 9.13+/-0.64 cm in Group I (P<0.01) and 9.49+/-1.05 cm in Group II (P<0.01) at 1 y after injection. Net increase of maximal glandular circumference after glans augmentation was 14.93+/-0.80 mm in Group I and 14.78+/-0.89 mm in Group II. In patient's visual estimation, more than 50% of injected volume was maintained in 95% of Group 1 and 100% of Group II. The percentage of postoperative satisfaction (Gr 4, 5) was 77% in Group 1 and 69% in Group II. There was no abnormal reaction in area feeling, texture, and color. In most cases, initial discoloration by glandular swelling recovered to normal within 2 weeks. There were no signs of inflammation and no serious adverse reactions in all cases. These results suggest that injectable hyaluronic acid gel is a safe and effective material for augmentation of glans penis.

Adult↗

Endothelial nitric oxide synthase protein expression, localization, and activity in the penis of the alloxan-induced diabetic rat.

PURPOSE: To explore the possible relevance of endothelial nitric oxide synthase (eNOS) in the pathophysiology of erectile dysfunction (ED) associated with diabetes mellitus, we compared the catalytic activity, protein expression, and cellular localization of eNOS with those of neuronal nitric oxide synthase (nNOS) in the penis of rats with alloxan-induced diabetes. MATERIALS AND METHODS: Adult male Sprague-Dawley rats were given alloxan or vehicle only and monitored weekly by Dextrostix for confirmation of glucosuria. Tail-flick immersion and penile reflex testing were used to evaluate sensory neuropathy and ED, respectively. At 4 to 5 weeks (early) and 10 to 11 weeks (late), animals were sacrificed, and their penes were subjected to nNOS and eNOS catalytic activity assay, Western immunoblotting, and immunohistochemistry examination. Masson's trichrome staining of penile tissue and serum testosterone measurements were performed for light microscopy and sex steroidogenic analysis, respectively. RESULTS: Confirmed diabetic rats showed significant reductions in penile nNOS expression and eNOS activity and expression early, prior to observed ED, and nNOS and eNOS activities and expressions late, synchronous with ED. Decreased intensities of both nNOS staining, localized to the dorsal and cavernosal nerves distributing to the penis, and eNOS staining, localized to penile vascular and sinusoidal endothelium, were assessed in diabetic animals. Penile vascular and cavernosal tissue appeared intact in diabetic rats. Testosterone levels were equivalent in nondiabetic and diabetic rats. CONCLUSIONS: In the penis of the alloxan-induced diabetic rat, eNOS protein expression and synthetic activity were reduced compared with the normal rat penis, independent of testosterone influence and in the absence of significant erectile tissue degenerative changes. These eNOS effects apparently preceded nNOS effects. Full elucidation of the possible mechanisms affecting eNOS function in the diabetic rat penis requires further investigation.

Alloxan↗

Trauma of the external genitalia in children: amputation of the penis and emasculation.

PURPOSE: Amputation of the penis or emasculation in children is rarely reported in the medical literature. This study involves 7 children with these injuries admitted to the University Hospital San Vicente de Paul, Medellin, Colombia, from 1960 to 1995. A new surgical technique is described for penile reconstruction that makes sex reassignment to the female gender unnecessary in most if not all cases. MATERIALS AND METHODS: Clinical histories and photographs of 7 boys 4 months to 8 years old with penile amputation or emasculation were reviewed. Five patients were younger than 1 year. Sex reassignment to the female gender was accepted by 1 family and refused by 4. Three boys were hospitalized at ages 3.5, 4 and 4.5 years, respectively, and underwent phalloplasty using the stumps of the remaining corpora cavernosa. The 2 older patients had been emasculated in accidents. In the 8-year-old patient the penis was reattached and the 7-year-old boy awaits myodermal flap phalloplasty. RESULTS: The boy raised in the female gender requested reassignment as a boy 14 years later. The 3 patients who underwent penile reconstruction were followed for 17, 12 and 8 years, respectively. At the last followup they emptied the bladder, and had normal skin sensitivity and erections. After 3 years the boy with a reattached penis has no problem emptying the bladder but he has lymphedema and decreased skin sensitivity. CONCLUSIONS: Phalloplasty using the remaining stumps of the corpora cavernosa should be first line therapy in children with traumatic loss of the penis. It restore the functional and cosmetic aspects of the organ, and makes sex reassignment to the female gender unnecessary. Replantation of the penis must be attempted when the amputated organ is recovered. A microvascular technique is recommended.

Amputation, Traumatic↗

Temporary ectopic implantation of an amputated penis.

A case of temporary ectopic implantation of an amputated penis to the forearm followed by subsequent return to its anatomic position is reported. The penis was amputated by a riding lawnmower, and massive contamination of the perineum and an extensive hematoma precluded immediate replantation. The penile vessels were attached to the radial artery and venae comitantes on the forearm, where it survived completely. After 4 weeks, the edema and hematoma of the perineum had resolved, and the penis was returned to its anatomic position by microsurgical technique. Arteries, veins, and nerves were repaired. The penis survived in its entirety. Return of sensation has been excellent. A urethrocutaneous fistula developed that required secondary closure with local flaps. Temporary ectopic replantation of the penis is a useful salvage procedure when the perineum is heavily contaminated or too extensively damaged for immediate replantation.

Adult↗

Identification of communicating branches among the dorsal, perineal and cavernous nerves of the penis.

PURPOSE: The mechanism of human erection requires the coordination of an intact neuronal system that includes the cavernous, perineal, and dorsal nerves of the penis. We defined the communication of these 3 nerves that travel under the pubic arch using specific neuronal immunohistochemical staining and 3-dimensional reconstruction imaging technique. MATERIALS AND METHODS: A total of 18 normal human fetal penile specimens at 17.5 to 32 weeks of gestation were studied by immunohistochemical techniques. Serial sections were stained with antibodies raised against the neuronal markers S-100, and neuronal nitric oxide synthase (nNOS), vesicular acetylcholine transporter (VAChT), calcitonin gene-related peptide and substance P. RESULTS: The continuation of the dorsal neurovascular bundle of the prostate was documented under the pubic arch. Two distinct nerve bundles were identified superior to the urethra and medial to the origin of the crural bodies. Nerve bundles were observed to join the corporeal bodies at the penile hilum. Proximal to the penile hilum the dorsal nerves stained only for S-100 and VAChT. From the junction of the crural bodies at the hilum to the glans penis dorsal nerve fibers stained positive for S-100, VAChT and nNOS. Calcitonin gene-related peptide and substance P demonstrated positive staining at the distal nerves, particularly at the glans. In contrast, the whole course of the cavernous nerve stained for S-100 and nNOS. Under the pubic arch at the penile hilum the cavernous nerves were found to convey nNOS positive branches to the dorsal nerve to transform its immunoreactivity to nNOS positive. Proximal nNOS negative perineal nerves were shown to stain positive for nNOS distal on the penis. Interaction between nNOS positive dorsal nerve branches and perineal nerves was at the cavernous-spongiosal junction, where the bulbospongiosus muscle terminates. CONCLUSIONS: At penile hilum, where the corporeal bodies start to separate, the cavernous nerve sends nNOS positive fibers to join the dorsal nerve of the penis, thereby, changing the functional characteristics of the distal penile dorsal nerve. Similarly the nNOS negative, ventrally located perineal nerve originating from the pudendal nerve becomes nNOS reactive at the cavernous-spongiosal junction. These 2 examples of redundant neuronal wiring in the penis may impact erectile function, especially during reconstructive surgery.

Calcitonin Gene-Related Peptide↗

Glans penis perception of Koro patients.

Koro is a form of sexual neurosis in which a reaction of acute anxiety accompanies the perception of decreased penis length from intra-abdominal traction. This study attempts to explore the glans penis perception of Koro patients by a grapho-motor projective test--DAPT (Draw-a-penis Test). This controlled DAPT investigation shows that Koro patients have significantly less perception of glans penis than the controls. This perceptual deviation in glans penis image is discussed in relation to the sexual-behavioral profile and Koro vulnerability of the patients.

Adult↗

Functional characterization of endothelin receptors in the bovine retractor penis muscle and penile artery.

The effects of endothelin-1 and sarafotoxin 6c on the bovine retractor penis muscle and the bovine penile artery were studied, and a functional characterization of endothelin receptors in these tissues was performed by using the ETA-receptor antagonist BQ-123 and the ETB-receptor antagonist IRL 1038. The retractor penis muscle and the penile artery were about equipotently contracted by endothelin-1 in a concentration-dependent manner the EC50 values being 3.5 x 10(-9) M and 1.3 x 10(-9) M, respectively. In both tissues BQ-123 (10(-6) M) inhibited maximal contraction induced by endothelin-1 by about 50%. Sarafotoxin 6c substantially relaxed the retractor penis muscle, and to a lesser extent also the penile artery, whereas endothelin-1 did not relax either tissue. The sarafotoxin 6c-induced relaxation of the retractor penis muscle was totally inhibited by IRL 1038 (3 x 10(-6) M) and the nitric oxide synthase inhibitor L-NNA (10(-4) M). In both tissues L-NNA enhanced the contraction induced by endothelin-1 and lowered the threshold concentration for it. The results show that in both tissues the contraction induced by endothelin-1 was mediated primarily by ETA-receptors. The retractor penis muscle is also equipped with ETB-receptors, probably at least in part located on the inhibitory nerves, which mediate relaxation via activation of the L-arginine nitric oxide synthase pathway.

Analysis of Variance↗

High frequency of postcoital penis cleaning in Budongo chimpanzees.

Cultural or tool use behaviours are typically conducted in social or food procurement contexts where the individual interacts with conspecifics, heterospecifics or environmental features. We report on postcoital penis cleaning in chimpanzees, an activity that does not fit this pattern. In penis cleaning, leaves are employed as 'napkins' to wipe clean the penis after sex. Alternatively, the same cleaning motion can be done without leaves, simply using the fingers. Not all chimpanzee communities studied across Africa clean their penes and, where documented, the behaviour is rare. By contrast, we identify postcoital penis cleaning in Budongo Forest, Uganda, as customary and corroborate penis cleaning as another cultural trait in chimpanzees, one that is specific to only a subset of the eastern subspecies of chimpanzee (Pan troglodytes schweinfurthii).

Animals↗

Pedicled rectus abdominis muscle flap wrapped around the penis for enhanced urethral pressure: an experimental study in dogs.

PURPOSE: It was the aim of this study to investigate the possibility of pedicled rectus abdominis muscle fascial flap wrapped around the penis for enhanced urethral pressure in dogs. MATERIALS AND METHODS: Ten adult male Beagle dogs underwent a procedure in which surrounding tissue of the penis at the site of the bulbomembranous urethra was dissected and a pedicled rectus abdominis muscle fascial flap was wrapped around the penis. Profilometry of the urethral pressure was carried out before, during and after the operation in all dogs. RESULTS: Before the operation, the mean maximal urethral pressure (MUP) was 48.9 +/- 11 cm H(2)O, and the mean MUP was 78.3 +/- 20.5 cm H(2)O after the penis was surrounded by a rectus muscle flap. There was a significant difference (t = 4.99, p = 0.0007). Ten weeks after the operation, the mean MUP was 88.3 +/- 22.4 cm H(2)O, which was significantly higher than that before the operation (t = 6.0584, p = 0.0002). CONCLUSIONS: A pedicled rectus abdominis muscle fascial flap wrapped around the penis can raise the urethral pressure. This provided an experiment basis for treating male urinary incontinence with a pedicled rectus muscle flap.

Animals↗

Evidence for a potential role of estrogen in the penis: detection of estrogen receptor-alpha and -beta messenger ribonucleic acid and protein.

Body tissues are traditionally classified as estrogen targets based on both the response to the hormone and the presence of estrogen receptors (ERs). We undertook the study on expression of ERalpha and ERbeta in the penis to identify compartments/cells responsive to estrogen, using immunohistochemistry, Western blotting, in situ hybridization, and RT-PCR analyses. Expressions of ERalpha and ERbeta in the rat penis were age dependent at both mRNA and protein levels, with the most intense signals being observed during the perinatal period and declining thereafter with age. Initial signals (fetal d 17) of ERalpha were localized to the mesenchyme and subepithelial stroma and later (postnatal d 2) to the corpus spongiosus, corpus cavernosus, and urethral epithelia. ERbeta was initially detected by postnatal d 2 and was localized diffusely in corpus spongiosus and cavernosus in immature rats. In the adult, both ERs were concentrated largely to the urethral epithelia and vascular and neuronal structures. The present study provides the first evidence for ER expression in the penis. Thus, our data add the penis to the list of estrogen-responsive tissues in males and provide a base and insight for future studies aimed at investigating a functional role of estrogen in the penis, especially in development.

Aging↗

Effects of tactile and electrical stimuli upon release of vasoactive intestinal polypeptide in the mammalian penis.

Plasma levels of vasoactive intestinal polypeptide (VIP) in the corpora cavernosa penis and dorsal penile veins greatly exceeded those measured in the limb or caudal veins during anaesthesia in various mammals (Bennett's wallaby, Barbary sheep, cheetah, puma, sooty mangabey, pigtail macaque and chimpanzee). Tactile stimulation of the penis immediately before or during collection of blood samples resulted in an increase. In the wallaby, VIP levels (mean +/- S.E.M.) in blood samples collected from the flaccid penis in the absence of tactile stimulation were very low (0.6 +/- 0.5 pmol/l). A 36-fold increase in VIP occurred after manual extension of the flaccid penis (24.8 +/- 3.2 pmol/l) or during manually stimulated erections (25.1 +/- 1.7 pmol/l). Electrical stimulation of erection produced no significant increase in VIP levels (2.3 +/- 0.9 pmol/l) unless accompanied by tactile stimulation (17.5 +/- 1.4 pmol/l). These studies provide the first demonstration that sensory feedback from the penis plays an important role in regulating vasoactive intestinal polypeptidergic activity. Since VIP is a potent vasodilator its release due to tactile stimuli during copulation may play a role in the maintenance of penile erection.

Acinonyx↗

The nitric oxide signaling pathway in the penis.

It is widely accepted that nitric oxide plays an important role in the biology of the penis, serving most familiarly as the agent responsible for penile erection. Early investigation in the field led to the identification of the signaling function of the molecule in the penis which yields corporal smooth muscle relaxation fundamental for the erectile response. Ongoing study of this molecule and its signaling pathway in erectile tissue has served to revise and clarify its importance. Current information conveys the prerequisite of the nitric oxide signaling pathway for penile erection, the regulatory basis for the generation and actions of nitric oxide in the penis, the diverse roles of its synthetic enzyme isoforms in penile biology, and the interaction between nitric oxide and other molecular pathways operative in the broad context of erection physiology. Insight into these subject areas has therapeutic relevance for pathologic conditions of the penis. The purpose of this review is to highlight the latest areas of investigation related to the science of nitric oxide in the penis, as a gateway for considering novel therapeutic strategies for erectile disorders now and in the future.

Humans↗

Surgical treatment of 45 horses affected by squamous cell carcinoma of the penis and prepuce.

The medical records of 45 horses treated for suspected squamous cell carcinoma of the penis and/or prepuce were reviewed. The age of 40 horses was known, and these had a mean age of 17.4 years. The duration of neoplasia was known for only 3 of the 45 horses. The results of histological evaluation of lesions, available for 35 horses, confirmed that the diseased tissue was squamous cell carcinoma. The location of gross neoplastic lesions was recorded for 43 horses; the glans penis was involved in 24 horses, the body of the penis or the inner lamina of the preputial fold in 27 horses, and the external fold of the prepuce in 10 horses. Surgical treatments of these horses included phallectomy (penile amputation) in 35 horses, segmental posthectomy in 4 horses, phallectomy plus segmental posthectomy in 2 horses, and en bloc resection of the penis, prepuce and superficial inguinal lymph nodes with penile retroversion in 4 cases. Short-term complications in the immediate postoperative period included preputial oedema and haemorrhage at the end of urination. One horse developed acute urinary retention because of severe urethral oedema. Long-term (>1 year) follow-up information was obtained for 31 horses. Neoplasia of the penis and/or prepuce recurred in 6 of these 31 horses (19%), and in 5 of these the recurrence necessitated euthanasia of the horse.

Animals↗