Targeting heme in sickle cell disease: new perspectives on priapism treatment.

Men with sickle cell disease (SCD) frequently experience priapism, defined as prolonged, painful erections occurring without sexual arousal or desire. This urological emergency can lead to penile fibrosis and permanent erectile dysfunction if not treated adequately. Due to its complex pathophysiology, there is currently no effective preventative treatment for this condition. Recent studies have highlighted the dysfunction of the nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) pathway in erectile tissues as a critical mechanism in developing priapism in SCD. Additionally, further research indicates that intravascular hemolysis promotes increased smooth muscle relaxation in the corpus cavernosum and that excess heme may significantly contribute to priapism in SCD. Pharmacological treatments should ideally target the pathophysiological basis of the disease. Agents that reduce excess free heme in the plasma have emerged as potential therapeutic candidates. This review explores the molecular mechanisms underlying the excess of heme in SCD and its contribution to developing priapism. We discuss pharmacological approaches targeting the excess free heme in the plasma, highlighting it as a potential therapeutic target for future interventions in managing priapism.

Soluble guanylate cyclase stimulators and activators: new horizons in the treatment of priapism associated with sickle cell disease.

Priapism, defined as a prolonged and often painful penile erection occurring without sexual stimulation or desire, is a common complication in sickle cell disease (SCD), affecting up to 48% of male patients. This condition presents significant clinical challenges and can lead to erectile dysfunction if not properly managed. Current pharmacological treatments for SCD-related priapism are primarily reactive rather than preventative, highlighting a gap in effective medical intervention strategies. A critical factor in developing priapism is the reduced basal bioavailability of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) in erectile tissues. New prevention strategies should ideally target the underlying pathophysiology of the disease. Compounds that stimulate and activate soluble guanylate cyclase (sGC) emerge as potential therapeutic candidates since these compounds have the property of inducing cGMP production by sGC. This review explores the potential of sGC stimulators and activators in treating priapism associated with SCD. We discuss the advantages of these agents in the face of the challenging pathophysiology of SCD. Additionally, the review underscores the impact of intravascular hemolysis and oxidative stress on priapism pathophysiology in SCD, areas in which sGC stimulators and activators may also have beneficial therapeutic effects.

Corpus cavernosum abscess after Al-Ghorab shunt with Snake Maneuver for ischemic priapism treatment: Clinical and surgical treatments.

Corpus cavernosum abscess is a rare condition that can lead to permanent and debilitating consequences. This case reports a 58-year-old man who developed erectile dysfunction with no response to oral and intracavernous medications after the surgical treatment of a penile abscess.

Bilateral partial thrombosis of the corpus cavernosum associated with the use of a stationary bike. Case report and literature review.

Partial and segmental thrombosis of the corpus cavernosum is a rare pathology not entirely understood, however, there are some triggers that have been associated in its appearance. We present a case of a 36-year-old patient with bilateral partial thrombosis of the corpus cavernosum, without priapism, after use of a stationary exercise bike. Ultrasound and magnetic resonance findings are shown, in which bilateral involvement stands out. The patient received conservative management with good response. This pathology is idiopathic and multiple factors have been associated to its origin, one of them being repetitive trauma due to sports activity.

NLRP3 activation contributes to endothelin-1-induced erectile dysfunction.

In the present study, we hypothesized that endothelin (ET) receptors (ETA and ETB ) stimulation, through increased calcium and ROS formation, leads to Nucleotide Oligomerization Domain-Like Receptor Family, Pyrin Domain Containing 3 (NLRP3) activation. Intracavernosal pressure (ICP/MAP) was measured in C57BL/6 (WT) mice. Functional and immunoblotting assays were performed in corpora cavernosa (CC) strips from WT, NLRP3-/- and caspase-/- mice in the presence of ET-1 (100 nM) and vehicle, MCC950, tiron, BAPTA AM, BQ123, or BQ788. ET-1 reduced the ICP/MAP in WT mice, and MCC950 prevented the ET-1 effect. ET-1 decreased CC ACh-, sodium nitroprusside (SNP)-induced relaxation, and increased caspase-1 expression. BQ123 an ETA receptor antagonist reversed the effect. The ETB receptor antagonist BQ788 also reversed ET-1 inhibition of ACh and SNP relaxation. Additionally, tiron, BAPTA AM, and NLRP3 genetic deletion prevented the ET-1-induced loss of ACh and SNP relaxation. Moreover, BQ123 diminished CC caspase-1 expression, while BQ788 increased caspase-1 and IL-1ß levels in a concentration-dependent manner (100 nM-10 µM). Furthermore, tiron and BAPTA AM prevented ET-1-induced increase in caspase-1. In addition, BAPTA AM blocked ET-1-induced ROS generation. In conclusion, ET-1-induced erectile dysfunction depends on ETA - and ETB -mediated activation of NLRP3 in mouse CC via Ca2+ -dependent ROS generation.

Inhibition of multidrug resistance proteins by MK571 restored the erectile function in obese mice through cGMP accumulation.

BACKGROUND: Intracellular levels of cyclic nucleotides can also be controlled by the action of multidrug resistance protein types 4 (MRP4) and 5 (MRP5). To date, no studies evaluated the role of their inhibition in an animal model of erectile dysfunction (ED). OBJECTIVES: To evaluate the effect of a 2-week treatment with MK571, an inhibitor of the efflux of cyclic nucleotides in the ED of obese mice. MATERIALS AND METHODS: Mice were divided in three groups: (i) lean, (ii) obese, and (iii) obese + MK571. The corpus cavernosum (CC) were isolated, and concentration-response curves to acetylcholine (ACh), sodium nitroprusside (SNP), and tadalafil in addition to electrical field stimulation (EFS) were carried out in phenylephrine pre-contracted tissues. Expression of ABCC4 and ABCC5, intracellular levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), the protein levels for pVASPSer157 and pVASPSer239 , and the intracavernous pressure (ICP) were also determined. The intracellular and extracellular (supernatant) ratios in CC from obese and lean stimulated with a cGMP-increasing substance (BAY 58-2667) in the absence and presence of MK571 (20 µM, 30 min) were also assessed. RESULTS: The treatment with MK571 completely reversed the lower relaxing responses induced by EFS, ACh, SNP, and tadalafil observed in obese mice CC in comparison with untreated obese mice. Cyclic GMP and p-VASPSer239 expression were significantly reduced in CC from obese groups. MK571 promoted a sixfold increase in cGMP without interfering in the protein expression of p-VASPSer239 . Neither the cAMP levels nor p-VASPSer157 were altered in MK571-treated animals. The ICP was ∼50% lower in obese than in the lean mice; however, the treatment with MK571 fully reversed this response. Expressions of ABCC4 and ABCC5 were not different between groups. The intra/extracellular ratio of cGMP was similar in CC from obese and lean mice stimulated with BAY 58-2667. CONCLUSIONS: The MRPs inhibition by MK571 favored the accumulation of cGMP in the smooth muscle cells, thus improving the smooth muscle relaxation and the erectile function in obese mice.

Corpus cavernosum abscess: A case report.

Corpus cavernosum abscess is a rare infection of the genitourinary tract. In this case report, we present a 42-year-old patient admitted with pain and edema in the penile shaft twenty-four days after drainage by puncture of the cavernous body due to ischemic priapism. Al-Ghorab procedure together snake-maneuver and broad-spectrum antibiotic therapy were performed. Despite manifesting erectile dysfunction, he evolved without penile deviations.

Association between partial thrombosis of the corpus cavernosum, partial priapism, and hard flaccid syndrome: A scoping review.

AIM: To describe the association between partial thrombosis of the corpus cavernosum, partial priapism, and hard flaccid syndrome. METHODS: A scoping review was performed according to the recommendations of the Joanna Briggs Institute. Moreover, we performed a search strategy using the MEDLINE, EMBASE, and CENTRAL databases. We included the available information, evaluating the conditions of partial thrombosis of the corpus cavernosum, partial priapism, and hard flaccid syndrome, and their molecular and physiological mechanisms and clinical presentation. RESULTS: We identified 207 articles and chose eight studies published between 2001 and 2021. The total number of patients was 34, and their mean age was 28.2 years. Moreover, in 84% of the studies, the pathophysiology of the events was related to microtrauma or prolonged perineal compression. Additionally, 94.2% of the patients had some degree of erectile dysfunction. In addition, out of all patients, 94% underwent magnetic resonance imaging (MRI). However, patients with hard flaccid syndrome did not show relevant findings in these studies. Conversely, MRI showed asymmetry in the proximal corpora cavernosa, thrombosed corpus cavernosum segments, and mainly cavernous fibrous septum in patients with partial cavernous thrombosis and partial priapism. CONCLUSION: Partial thrombosis of the corpus cavernosum, partial priapism, and hard flaccid syndrome occurred more frequently in young patients, possibly related to microtraumas that generate cavernous fibrosis and trigger alterations in the erection of the distal portion of the penis. Additionally, they cause proximal hardening of the pelvis, perineal pain, painful ejaculations, and cavernous asymmetry. Moreover, the imaging characteristics are similar in patients with partial priapism and partial cavernous thrombosis.

Guanosine, a guanine-based nucleoside relaxed isolated corpus cavernosum from mice through cGMP accumulation.

In corpus cavernosum (CC), guanosine triphosphate (GTP) is converted into cyclic guanosine monophosphate (cGMP) to induce erection. The action of cGMP is terminated by phosphodiesterases and efflux transporters, which pump cGMP out of the cell. The nucleotides, GTP, and cGMP were detected in the extracellular space, and their hydrolysis lead to the formation of intermediate products, among them guanosine. Therefore, our study aims to pharmacologically characterize the effect of guanosine in isolated CC from mice. The penis was isolated and functional and biochemical analyses were carried out. The guanine-based nucleotides GTP, guanosine diphosphate, guanosine monophosphate, and cGMP relaxed mice corpus cavernosum, but the relaxation (90.7 ± 12.5%) induced by guanosine (0.000001-1 mM) was greater than that of the nucleotides (~ 45%, P < 0.05). Guanosine-induced relaxation was not altered in the presence of adenosine type 2A and 2B receptor antagonists. No augment was observed in the intracellular levels of cyclic adenosine monophosphate in tissues stimulated with guanosine. Inhibitors of nitric oxide synthase (L-NAME, 100 µM) and soluble guanylate cyclase (ODQ, 10 µM) produced a significant reduction in guanosine-induced relaxation in all concentrations studied, while in the presence of tadalafil (300 nM), a significant increase was observed. Pre-incubation of guanosine (100 µM) produced a 6.6-leftward shift in tadalafil-induced relaxation. The intracellular levels of cGMP were greater when CC was stimulated with guanosine. Inhibitors of ecto-nucleotidases and xanthine oxidase did not interfere in the response induced by guanosine. In conclusion, our study shows that guanosine relaxes mice CC and opens the possibility to test its role in models of erectile dysfunction.

Evaluation of the effects of chronic stress applied from the prepubertal to the adult stages or only during adulthood on penile morphology in rats.

The present study aimed to evaluate the effects of chronic stress from the prepubertal to the adult stages or during adulthood on penile morphology in rats. The animals were immobilized in a cylinder for 2 h daily for a total of six weeks to simulate stress. Ten rats were exposed to stress stimulus beginning from the prepubertal age, while nine rats were exposed to stress stimulus only during adulthood. Animals were killed at 24 h after the last stress session for short-term evaluation (SP-S and SA-S), while other age-matched rats were sacrificed at 6 weeks after the last stress session for long-term evaluation (SP-L and SA-L). Age-matched animals were used as controls (CP-S, CA-S, CP-L and CA-L). After treatment, serum testosterone levels and areas of cavernosum structures were evaluated. We observed no changes in serum testosterone levels after stress treatment. Results revealed that the area of the corpus cavernosum without the tunica albuginea in animals in the SA-S group was 16% lower than that in the CA-S group. The smooth muscle was 31% lower in the SP-L group than in the SP-S group and 42% lower in the SA-S group than in the CA-S group. The elastic fiber system was 48% lower in the SP-L group than in the CP-L group and 59% lower in the SA-S group than in the CA-S group. Chronic stress promoted morphological changes in the rat penis and was significantly more pronounced when the stress occurred throughout the adulthood. Chronically applied single stress stimulus caused greater damage to the penis when induced directly during adulthood than when introduced before puberty to adulthood and could be associated with erectile dysfunction.

Expression profile of endothelin receptors (ETA and ETB) and microRNAs-155 and -199 in the corpus cavernosum of rats submitted to chronic alcoholism and diabetes mellitus

Recent evidence shows that chronic ethanol consumption increases endothelin (ET)-1 induced sustained contraction of trabecular smooth muscle cells of the corpora cavernosa in corpus cavernosum of rats by a mechanism that involves increased expression of ETA and ETB receptors. Our goal was to evaluate the effects of alcohol and diabetes and their relationship to miRNA-155, miRNA-199 and endothelin receptors in the corpus cavernosum and blood of rats submitted to the experimental model of diabetes mellitus and chronic alcoholism. Forty-eight male Wistar rats were divided into four groups: control (C), alcoholic (A), diabetic (D), and alcoholic-diabetic (AD). Samples of the corpus cavernosum were prepared to study the protein expression of endothelin receptors by immunohistochemistry and expression of miRNAs-155 and -199 in serum and the cavernous tissue. Immunostaining for endothelin receptors was markedly higher in the A, D, and AD groups than in the C group. Moreover, a significant hypoexpression of the miRNA-199 in the corpus cavernosum tissue from the AD group was observed, compared to the C group. When analyzing the microRNA profile in blood, a significant hypoexpression of miRNA-155 in the AD group was observed compared to the C group. The miRNA-199 analysis demonstrated significant hypoexpression in D and AD groups compared to the C group. Our findings in corpus cavernosum showed downregulated miRNA-155 and miRNA-199 levels associated with upregulated protein expression and unaltered mRNA expression of ET receptors suggesting decreased ET receptor turnover, which can contribute to erectile dysfunction in diabetic rats exposed to high alcohol levels.

Hypercaloric Diet Establishes Erectile Dysfunction in Rat: Mechanisms Underlying the Endothelial Damage.

Obesity is characterized by an excessive increase in body mass, leading to endothelial damage that may favor the development of erectile dysfunction (ED). ED is defined as the inability to achieve or maintain a penile erection long enough to have a sexual intercourse. In this context, different ED models were developed, however the high price of special animals or the long period to establish the disease has limited studies in this field. Therefore, this study proposed to establish and characterize a novel model of ED in rats associated to a hypercaloric diet consumption. Animals were randomly divided into control group (CG), which received a standard diet, and obese group (OG), fed with a hypercaloric diet during 8 weeks. Rat's erectile function was evaluated in vivo and in vitro. Food and caloric intake of OG were reduced compared to CG, due to an increased diet energy efficiency. However, OG presented an increased body mass, inguinal, retroperitoneal and epididymal adipose tissues, as well as body adiposity index at the end of experimental protocol. In erectile function analysis, there was a decrease in the number and the latency of penile erections in OG. Additionally, the contractile reactivity of corpus cavernosum was increased in OG, favoring penile detumescence and related to a reduced nitric oxide bioavailability and an increased in contractile prostaglandins levels as a consequence of endothelial damage. Moreover, the endothelium-relaxation reactivity of corpus cavernosum was attenuated in OG associated to the oxidative stress. Thus, it was provided a model for advances in sexual dysfunction field and drug discovery for ED treatment.

Testosterone replacement maintains smooth muscle content in the corpus cavernosum of orchiectomized rats.

OBJECTIVE: To evaluate the effects of testosterone (T) on the maintenance of corpus cavernosum (CC) structure and apoptosis. METHODS: Animals were divided into three groups: sham operation group (n = 8) underwent sham operation; Orchiectomized (Orchiec)+ oily vehicle group (n = 8) underwent bilateral orchiectomy and received a single dose of oily vehicle by intramuscular injection (i.m.) 30 days after orchiectomy; and Orchiec + T group (n = 8) underwent bilateral orchiectomy and received a single dose of T undecanoate 100 mg/kg i.m. 30 days after the surgery. Animals were euthanized 60 days after the beginning of the experiment with an anesthetic overdose of ketamine and xylazine. Blood samples and penile tissue were collected on euthanasia. Azan's trichrome staining was used to evaluate smooth muscle, Weigert's Fucsin-Resorcin staining was used to evaluate elastic fibers and Picrosirius red staining was used to evaluate collagen. Apoptosis was evaluated using TUNEL technique. RESULTS: T levels decreased in Orchiec + oily vehicle when compared to sham operation and Orchiec + T groups (p < 0.001). T deprivation reduced trabecular smooth muscle content and penile diameter and T replacement maintained both parameters (p = 0.005 and p = 0.001, respectively). No difference was observed in the content of sinusoidal space (p = 0.207), elastic fibers (p = 0.849), collagen (p = 0.216) and in apoptosis (p = 0.095). CONCLUSION: Normal testosterone levels maintain CC smooth muscle content and do not influence elastic fibers, collagen content and apoptotic index. Further studies should be performed in order to investigate the mechanisms by which androgen mediates its effects on CC structure.

Hydrochlorothiazide Potentiates Contractile Activity of Mouse Cavernosal Smooth Muscle.

INTRODUCTION: Hydrochlorothiazide has a negative influence on penile erection but little is known about the mechanism(s) involved. AIMS: To characterize the effects of this diuretic on mouse corpus cavernosum (CC) smooth muscle in vitro and ex vivo. METHODS: CC strips of C57BL/6 mice (12-16 weeks old) were mounted in organ baths containing Krebs-Henseleit solution and tissue reactivity was evaluated. Expression of genes encoding diuretic targets and enzymes involved in penile erection were evaluated by polymerase chain reaction. MAIN OUTCOME MEASURES: Stimulation-response curves to phenylephrine (10 nmol/L-100 µmol/L) or to electrical field stimulation (1-32 Hz) were constructed, with or without hydrochlorothiazide. Strips of CC from mice after long-term hydrochlorothiazide treatment (6 mg/kg/day for 4 weeks) with or without amiloride (0.6 mg/kg/day for 4 weeks) in vivo also were studied. Nitric oxide and Rho-kinase pathways were evaluated. RESULTS: Hydrochlorothiazide (100 µmol/L) increased the maximum response to phenylephrine by 64% in vitro. This effect was unaffected by the addition of indomethacin (5 µmol/L) but was abolished by N((ω))-nitro-L-arginine methyl ester (100 µmol/L). Hydrochlorothiazide (100 µmol/L) potentiated electrical field stimulation-induced contraction in vitro, but not ex vivo. Long-term treatment with hydrochlorothiazide increased the maximum response to phenylephrine by 60% and resulted in a plasma concentration of 500 ± 180 nmol/L. Amiloride (100µmol/L) caused rightward shifts in concentration-response curves to phenylephrine in vitro. Long-term treatment with hydrochlorothiazide plus amiloride did not significantly increase the maximum response to phenylephrine (+13%). Reverse transcriptase polymerase chain reaction did not detect the NaCl cotransporter in mouse CC. Hydrochlorothiazide did not change Rho-kinase activity, whereas amiloride decreased it in vitro and ex vivo (approximately 18% and 24% respectively). A 40% decrease in Rock1 expression also was observed after long-term treatment with hydrochlorothiazide plus amiloride. CONCLUSION: Hydrochlorothiazide potentiates contraction of smooth muscle from mouse CC. These findings could explain why diuretics such as hydrochlorothiazide are associated with erectile dysfunction.

Consequence of hyperhomocysteinaemia on α1-adrenoceptor-mediated contraction in the rat corpus cavernosum: the role of reactive oxygen species.

OBJECTIVES: Our main objective was to investigate the mechanisms underlying the effects of hyperhomocysteinaemia (HHcy) on contractile response mediated by α1-adrenoceptors in the rat corpus cavernosum. METHODS: Concentration-response curves for phenylephrine (PE) were obtained in strips of corpus cavernosum, in absence or after incubation with tiron, tempol or polyethylene glycol (PEG)-catalase combined or not with tempol. We also measured the superoxide anion (O2(-)) and hydrogen peroxide (H2O2) generation, superoxide dismutase (SOD) and catalase activity and α-actin expression in rat corpus cavernosum from both groups. KEY FINDINGS: HHcy increased PE-induced contraction in cavernosal strips. Tiron, PEG-catalase or tempol increased PE-induced contraction in strips from control rats, but it was not altered by tiron or PEG-catalase in HHcy rats, whereas tempol reduced this response. The combination of PEG-catalase and tempol did not alter the contractile response to PE in both groups. HHcy increased O2(-) generation and SOD activity, whereas H2O2 concentration was reduced. Finally, HHcy did not alter catalase activity or expression of α-actin. CONCLUSIONS: The major new finding from this study is that HHcy induced a marked increase in PE-induced contraction in rat corpus cavernosum by a mechanism that involves increased O2(-) generation and it could play a role in the pathogenesis of erectile dysfunction associated with HHcy.

Pharmacological characterisation of the relaxation induced by the soluble guanylate cyclase activator, BAY 60-2770 in rabbit corpus cavernosum.

OBJECTIVE: To characterise the relaxation induced by the soluble guanylate cyclase (sGC) activator, BAY 60-2770 (4-({(4-carboxybutyl) [2- (5-fluoro-2-{[4'-(trifluoromethyl) biphenyl-4-yl]methoxy}phenyl)ethyl] amino}methyl)benzoic acid) in rabbit corpus cavernosum (CC). MATERIAL AND METHODS: The penis from male New Zealand rabbits was removed and fours strips of CC were obtained. Concentration-response curves to BAY 60-2770 were constructed in the absence and presence of inhibitors of nitric oxide synthase, N (G)-nitro-L- arginine methyl ester (L-NAME, 100 µm), sGC, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 µm) and phosphodiesterase type 5 (PDE-5), tadalafil (0.1 µm). The potency (pEC50 ) and maximal response (Emax ) values were determined. Then, electrical-field stimulation (EFS)-induced contraction or relaxation was tested in the absence and presence of BAY 60-2770 (0.1 or 1 µm) alone or combined with ODQ (10 µm). For EFS-induced relaxation two protocols were used: (i) ODQ (10 µm) was first incubated for 20 min and then BAY 60-2770 (1 µm) was added for another 20 min (ODQ + BAY 60-2770); (ii) in different CC strips, BAY 60-2770 was incubated for 20 min followed by another 20 min with ODQ (BAY 60-2770 + ODQ). The intracellular levels of cyclic guanosine monophosphate (cGMP) were also determined. RESULTS: BAY 60-2770 potently relaxed rabbit CC with mean (sem) pEC50 and Emax values of 7.58 (0.19) and 81 (4)%, respectively. The inhibitors ODQ (n = 7) or tadalafil (n = 7) produced 4.2- and 6.3-leftward shifts, respectively in BAY 60-2770-induced relaxation without interfering with the Emax values. The intracellular levels of cGMP were augmented after stimulation with BAY 60-2770 (1 µm) alone, whereas its co-incubation with ODQ produced even higher levels of cGMP. The EFS-induced contraction was reduced in the presence of BAY 60-2770 (1 µm) and this inhibition was even greater when BAY 60-2770 was co-incubated with ODQ. The nitrergic stimulation induced CC relaxation, which was abolished in the presence of ODQ. BAY 60-2770 alone increased the amplitude of relaxation. Co-incubation of ODQ and BAY 60-2770 did not alter the relaxation in comparison with ODQ alone. Interestingly, when BAY 60-2770 was incubated before ODQ, EFS-induced relaxation was partly restored in comparison with ODQ alone or ODQ + BAY 60-2770. CONCLUSIONS: The relaxation induced by the sGC activator, BAY 60-2770 was increased after sGC oxidation and unaltered in the absence of nitric oxide. Thus, this class of substances may have advantages over sGC stimulators or PDE-5 inhibitors for treating patients with erectile dysfunction and extensive endothelial damage.

Prolonged therapy with the soluble guanylyl cyclase activator BAY 60-2770 restores the erectile function in obese mice.

INTRODUCTION: Cardiovascular and endocrine-metabolic diseases associated with increased oxidative stress such as obesity lead to erectile dysfunction (ED). Activators of soluble guanylyl cyclase (sGC) such as BAY 60-2770 reactivate the heme-oxidized sGC in vascular diseases. AIM: This study aimed to evaluate the effects of 2-week oral intake with BAY 60-2270 on a murine model of obesity-associated ED. METHODS: C57BL/6 male mice were fed for 12 weeks with standard chow or high-fat diet. Lean and obese mice were treated with BAY 60-2770 (1 mg/kg/day, 2 weeks). MAIN OUTCOME MEASURES: Measurements of intracavernosal pressure (ICP), along with acetylcholine (10(-9) to 10(-5) M) and electrical field stimulation (EFS; 4-10 Hz)-induced corpus cavernosum relaxations in vitro, were obtained. Levels of cyclic guanosine monophosphate (cGMP), reactive oxygen species (ROS), and sGC protein expressions in cavernosal tissues were measured. RESULTS: Cavernous nerve stimulation caused frequency-dependent ICP increases, which were significantly lower in obese compared with lean mice (P < 0.05). Two-week therapy with BAY 60-2770 fully reversed the decreased ICP in obese group. Acetylcholine-induced cavernosal relaxations were 45% lower (P < 0.001) in obese mice, which were fully restored by BAY 60-2770 treatment. Likewise, the EFS-induced relaxations in obese mice were restored by BAY 60-2770. Basal cGMP content in erectile tissue was 68% lower (P < 0.05) in obese mice, an effect normalized by BAY 60-2770. Levels of ROS were 52% higher (P < 0.05) whereas protein expression of α1 sGC subunit was reduced in cavernosal tissue of obese mice, both of which were normalized by BAY 60-2770. In lean group, BAY 60-2770 did not significantly affect any functional, biochemical, or molecular parameter analyzed. CONCLUSIONS: Two-week therapy with BAY 60-2770 restores the erectile function in obese mice that is associated with reduced ROS levels, up-regulation of α1 sGC subunit, and increased cGMP levels in the erectile tissue.

Fracturas del pene / Penile fracture

Background: Penile fracture occurs when the erect penis is bent suddenly and forcefully, rupturing the tunica albuginea of one or both of the corpus cavernosum. A delay in its treatment may lead to functional and morphological sequelae. Case reports: We report five patients aged 26 to 44 years with penile fracture and right corpus cavernosum involvement. All patients excepting one had felt pain. An emergency ultrasound was done in three cases to confirm the diagnosis and the extension of the lesion. All were operated, had an uneventful postoperative period and are currently asymptomatic.

Introducción: La fractura del cuerpo cavernoso representa una urgencia urológica infrecuente pero grave, ya que la lesión de estructuras cercanas y una demora en su tratamiento suele generar complicaciones morfológicas y funcionales irreversibles. Casos clínicos: Registramos 5 casos de fractura peneana en nuestro hospital en el período 2008-2012, con afectación del cuerpo cavernoso derecho y hematoma asociado en todos ellos. La edad promedio fue de 33,5 (rango 26-44) años. Todos relataron los síntomas característicos excepto uno, que permaneció sin dolor. Se realizó una ecografía urgente en 3 casos para confirmar el diagnóstico y evaluar la extensión de la lesión. Los pacientes fueron intervenidos quirúrgicamente de urgencia, el postoperatorio transcurrió sin incidencias y actualmente todos se encuentran asintomáticos.

Age-related changes in the concentration of elastic fibers in different regions of the rabbit penis

PURPOSE: To investigate whether elastic fiber content in the corpus cavernosum (CC), corpus spongiosum (CS) and tunica albuginea (TA) of the rabbit penis undergoes modifications with age. METHODS: Rabbits were sacrificed, in groups of ten animals each, at 30, 120, 240, and 730 days of age. Histological sections were obtained from the penile middle shaft and were stained with Weigert's resorsin fuchsin. The content of elastic fibers was determined using stereological methods, and was expressed as volume fraction. RESULTS: At 730 days of age, elastic fiber content was increased by 54% (p<0.004), 78% (p<0.004), and 87% (p<0.004) in the TA, CC, and CS, respectively, compared with animals aged 30 days. After 30 days of age, the concentration gradually and significantly increased until 240 days of age. In 730-day old animals, the concentration, compared with the previous age group, was unchanged in the CC and decreased by 20% (p<0.004) in the TA. CONCLUSIONS: Elastic fiber contents in the rabbit penis correlate with properties of penile tissues. Although after one month of age there is a gradual increase in these concentrations, in two-year old animals this trend is interrupted, which suggests that this could be an early alteration due to senescence.

Desenvolvimento do pênis durante o período fetal humano (13 a 36 semanas pós-concepção) / Penile development during the fetal period in humans (13 to 36 weeks post conception)

Objetivo: Analisar, em fetos humanos, o crescimento da área do pênis, da túnica albugínea e das estruturas eréteis (corpos cavernosos e corpo esponjoso), bem como o aparecimento e modificações das principais estruturas que compõem estes tecidos (colágeno, músculo liso e fibra elástica) durante o período fetal (13 a 36 semanas pós-concepção), fornecendo padrões normativos de crescimento. Material e Métodos: Foram utilizados 56 fetos humanos do sexo masculino com idade gestacional compreendida entre 13 e 36 semanas pós-concepção (SPC). Foram utilizadas técnicas histoquímicas, imunohistoquímicas, e análises morfométricas, e analisados os seguintes parâmetros: área total do pênis, área do corpo cavernoso, área do corpo esponjoso e a espessura da túnica albugínea na região dorsal e ventral do corpo cavernoso. No corpo cavernoso e no corpo esponjoso, as fibras musculares, o colágeno e as fibras do sistema elástico, foram identificados e quantificados por percentagem, no programa Image J (NIH, Bethesda, EUA).Resultados: Da 13ª à 36ª semana pós-concepção, a área do pênis variou de 0,95mm2 a 24,25mm2. No mesmo período a área do corpo cavernoso variou de 0,28mm2 a 9,12mm2 e a área do corpo esponjoso de 0,14mm2 a 3,99mm2. No corpo cavernoso a percentagem de fibras colágenas, fibras musculares e fibras do sistema elástico variaram, respectivamente, de 19,88% a 36,60%, de 4,39 % a 29,76 % e de 1,91% a 8,92%. No corpo esponjoso a percentagem de fibras colágenas, fibras musculares e fibras do sistema elástico variaram, respectivamente de 34,65% a 45,89%, de 0,60% a 11,90% e de 3,22% a 11,93%. A espessura da túnica albugínea variou de 0,029 a 0,296 na região dorsal e de 0,014 a 0,113 na região ventral do corpo cavernoso.Conclusão: Existe correlação fortemente positiva entre o crescimento da área total, da área do corpo cavernoso e da área do corpo esponjoso, com a idade gestacional, assim como existe correlação entre o crescimento dos elementos constituintes do tecido...

Objective: To analyze the development of penile area, tunica albuginea thickness and the main components of the erectile tissue, such as collagen, smooth muscle and elastic system fibers, in human fetuses, in order to provide normative parameters of development. Material and Methods: We studied 56 male human fetuses aged 13 to 36 weeks postconception (WPC). We used histochemical, immunohistochemical and morphometric techniques to analyze the following parameters: total penile area, area of the corpora cavernosa, area of the corpus spongiosum and thickness of tunica albuginea in the dorsal and ventral region. In the corpora cavernosa and in the corpus spongiosum, the collagen, smooth muscle fibers and elastic system fibers were identified and quantified as percentage by using the Image J software (NIH, Bethesda, USA).Results: From 13 to 36 WPC, the area of the penis varied from 0.95 mm2 to 24.25 mm2. Also, the area of the corpora cavernosa varied from 0.28 mm2 to 9.12 mm2 and the area of the corpus spongiosum from 0.14 mm2 to 3.99 mm2. In the corpora cavernosa, the amount of collagen, smooth muscle fibers and elastic system fibers varied from 19.88% to 36.60%, from 4.39 % to 29.76 % and from 1.91% to 8.92%, respectively. In the corpus spongiosum, the amount of collagen, smooth muscle fibers and elastic system fibers varied from 34.65% to 45.89%, from 0.60% to 11.90% and from 3.22% to 11.93%, respectively. The thickness of the tunica albuginea varied from 0.029 to 0.296 in the dorsal region and from 0.014 to 0.113 in the ventral region of the corpora cavernosa. Conclusion: We found strong correlation between the total area, the corpora cavernosa and the corpus spongiosum penile area, with the fetal age in WPC, as well as between collagen, smooth muscle and elastic fibers with fetal age in WPC. The growth rate was more intense during the 2nd trimester (13 to 24 WPC) of gestation when compared to the 3rd trimester (25 to 36 WPC). The thickness of the tunica...