Investigation of gene expression and genetic simultaneous control associated with erectile dysfunction and diabetes.

Diabetes can cause some diseases or abnormalities. One of the disorders caused by diabetes may be erectile dysfunction (ED). ED is sexual dysfunction characterized by the inability to establish or maintain an erect penis during sexual activity and is a common problem of men with chronic type 2 diabetes. These processes, disorders and diseases are highly influenced by the genetics of individuals. In this study, the relationship between genes and diabetes and ED has been explored by a system biology approach. For this purpose, the samples from ten control and diabetic-ED rats were collected. After a search in Gene Expression Omnibus (GEO), series with accession number GSE2457 comprising of 5 normal and 5 diabetic-ED rats were selected. Raw CEL files of these samples were normalized with robust multi-array average (RMA) expression measure method by using the linear models for microarray data (LIMMA) R package. The extracted probe IDs were transformed into 10451 unique and validated official gene symbols. Then, differentially expressed genes (DEGs) were identified between control and normal penile mucosa by employing the LIMMA R package. DEGs were classified by utilizing KEGG to underlying pathways by Enrichr. The expression values of DEGs were used to construct a gene regulatory network (GRN), by the GENEI3 R package. To analyze the topology of constructed GRNs, betweenness centrality was calculated. Genes with higher betweenness centrality scores were then identified, through the CytoNCA. We then took the commonality of DEGs genes and high-top ranking genes from CytoNCA via a predicted interaction network using GeneMANIA as the most likely important genes in erectile dysfunction. Among the 374 DEGs studied, 146 DEGs showed up-regulation and 228 DEGs displayed down-regulation expression in diabetic-ED rats. According to the Volcano plot, the dpp4, LOC102553868, Ndufa412, Oxct1, Atp2b3 and Zfp91 gene down-regulated and Lpl, Retsat, B4galt1 and Pdk4 genes up-regulated in ED and diabetic rats. Furthermore, genes like dpp4 acted as hubs in the inferred GRN.

Androgen regulated protein and pyruvate dehydrogenase kinase 4 in severe erectile dysfunction: A gene expression analysis, and computational study of protein structure.

Erectile dysfunction (ED) is one of the most common sexual disorders in men. During the past 30 years, there has been no new drug development for ED. Thus, exploring the genetic basis of ED deserves further study, in hope of developing new pharmacological treatments for ED. In this study, Real-Time PCR analysis was used to assess the expression of androgen regulatory protein (Andpro) and pyruvate dehydrogenase kinase 4 (Pdk4) genes in ED. For this purpose, the experiment was performed on 20 men with severe ED and 20 potent men. IIEF-15 was used to determine the ED severity. The study was conducted in the Department of Sexual Medicine of the Kermanshah University of Medical Sciences, Kermanshah, Iran. The EDTA-Na vacuum blood tube was taken from ED patients and controls. Informed consent was obtained from all participants. After blood sampling, RNA was extracted from whole blood. Then cDNA was synthesized. The gene expression was analyzed through the qPCR method. The ß-actin was used as a reference gene. To further study these two proteins, their three-dimensional structures were predicted through I-TASSER. Compared with controls, in ED patients, the expression of the Andpro gene decreased, while the expression of the Pdk4 gene increased (p<0.01). Predicting the structure of the protein showed that Pyruvate Dehydrogenase Kinase 4 had a double subunit and androgen-regulated protein had a single subunit.

A genome-wide association study to identify candidate genes for erectile dysfunction.

Erectile dysfunction (ED) can be caused by different diseases and controlled by several genetic networks. In this study, to identify the genes related to ED, the expression profiles of normal and ED samples were investigated by the Gene Expression Omnibus (GEO) database. Seventeen genes were identified as associated genes with ED. The protein and nucleic acid sequences of selected genes were retrieved from the UCSC database. Selected genes were diverse according to their physicochemical properties and functions. Category function revealed that selected genes are involved in pathways related to humans some diseases. Furthermore, based on protein interactions, genes associated with the insulin pathway had the greatest interaction with the studied genes. To identify the common cis-regulatory elements, the promoter site of the selected genes was retrieved from the UCSC database. The Gapped Local Alignment of Motifs tool was used for finding common conserved motifs into the promoter site of selected genes. Besides, INSR protein as an insulin receptor precursor showed a high potential site for posttranslation modifications, including phosphorylation and N-glycosylation. Also, in this study, two Guanine-Cytosine (GC)-rich regions were identified as conserved motifs in the upstream of studied genes which can be involved in regulating the expression of genes associated with ED. Also, the conserved binding site of miR-29-3p that is involved in various cancers was observed in the 3' untranslated region of genes associated with ED. Our study introduced new genes associated with ED, which can be good candidates for further analyzing related to human ED.

For Debate: Should We Worry about Hematospermia in Adolescents and Young Men? A Report of Six Cases and Review of the Literature.

Hematospermia or hemospermia is defined as the presence of blood in ejaculate. The true prevalence of the condition is unknown because many cases escape the patient's notice, and remain unrecognized and unreported. There are two main aims in the patient evaluation: first, to ensure that there is no specific condition that is treatable; second, to reassure the patient's parents that no causative factor is present. Many physicians are unfamiliar with this disorder and this forms the basis for our current review. We performed an essentially English language search (Medline since 1966 to present and reference list of articles) for "hematospermia", or "hemospermia" in combination with "adolescents", "young adults", "genital diseases", "management" and "review". The authors' personal experience with 6 adolescents and young men (up to the age of 20 years) is also reported. Several anatomical structures contributing to the ejaculate may be the source of the hematospermia: seminal vesicles, prostate, testis and epididymis. Hematospermia is a generally benign and self-limited condition that is infrequently associated with significant underlying pathology. Once the diagnosis is clear, it is important to reassure the adolescent about the benign nature and self-limiting course of the condition and to provide appropriate treatment to help ensure the adolescent's normal sexual development.

Postcoital penile drug eruption in a co-trimoxazole-sensitive patient following vaginal use of triple sulfa vaginal cream by his partner.

INTRODUCTION: This is a report of a very rare case of proven postcoital penile drug eruption in a patient following vaginal use of triple sulfa vaginal cream by his partner. AIM: To report the rare case of cross-reaction following vaginal use of triple sulfa vaginal cream in partner. METHODS: A case of postcoital penile drug eruption in a patient following vaginal use of triple sulfa vaginal cream in his partner is presented including subjective reporting, physical examination, and laboratory evaluations. RESULTS: We report a 42-year-old man with known sensitivity to trimethoprim/sulfamethoxazole (co-trimoxazole) who developed a penile drug eruption at the glans after having intercourse with his wife, who was taking sulfathiazole/sulfacetamide/sulfabenzamide (triple sulfa) vaginal cream. The nature of the lesion was confirmed by a rechallenge test. CONCLUSION: To our knowledge, this is the fourth case of proven postcoital penile drug eruption in a patient following vaginal use of triple sulfa vaginal cream in his partner. Our case illustrates the importance of history taking. In clinical practice of urology, it is not rare to see patients who present with strange penile lesions following coitus. To reach a correct diagnosis, one should obtain a drug history of the sexual partner and allergic history of the patient in such cases.

Nonischemic priapism following penile tattooing.

INTRODUCTION: To our knowledge, here we report the first case of nonischemic priapism following penile tattooing. AIM: To report the first case of nonischemic priapism following penile tattooing. METHODS: A case with tattooing-induced priapism is presented including subjective reporting, physical examination, and laboratory/radiologic evaluations. RESULTS: A 21-year-old man, presented with partially rigid penis of 3-month duration. On examination, the penis was half rigid, with a tattoo on its dorsal surface, and a smaller tattoo on the glans (Figure 1). The patient initially stated that the tattoo had been created years ago, but later admitted that he had it created just before the occurrence of priapism. A traditional tattooist created the tattoo manually, using a handheld needle. Bleeding from deep penile tissue for several days complicated the tattooing. Known etiologies of priapism were investigated and ruled out. Specifically, perineal injury, leukemia, sickle cell trait, thalassemia, urinary tract infection, neurogenic, neoplastic, infectious, toxic, and pharmacological causes were actively investigated and ruled out. There was no history of alcohol consumption or smoking. Aspirated penile blood was bright red. Cavernous blood gas measurements confirmed high oxygen and low carbon dioxide content, diagnostic of arterial priapism. There was no embolization facility in Kermanshah. In fact, there are few experts in superselective embolization in Iran. We referred the patient for superselective embolization. However, he underwent a nonindicated Sacher procedure. Predictably, the procedure was unsuccessful. At present, the patient continues to have priapism. Because of the painless nature of erections, moderately good preservation of erectile function during intercourses, and disappointment with former surgery, the patient declined further therapies, and he lives with his condition. CONCLUSIONS: Tattooing should be added to the etiologies of nonischemic priapism. Considering this case, we discourage penile tattooing.

Gender differences in subcutaneous and perirenal fat distribution.

PURPOSE: Body mass index (BMI) has been shown to influence the outcome of various surgical procedures. The purpose of this study is to assess the relationship between BMI, gender, and the distribution of subcutaneous and perirenal fat. METHODS: A retrospective review was performed for 123 patients who underwent radical or partial nephrectomy. Preoperative CT scans were reviewed by two independent observers. Subcutaneous fat was measured at three locations and perirenal fat was measured at six locations. Statistical analysis was performed using the Student's t test and the Pearson's correlation coefficient. RESULTS: Mean anterior subcutaneous fat was significantly greater in females than in males (2.54 vs. 1.78 cm, p < 0.001) as was mean right posterolateral subcutaneous fat (2.78 vs. 2.21 cm, p = 0.03). With regard to perirenal fat, men were greater than women for all perirenal locations around the left kidney. For the right kidney, men were greater than women for four out of six perirenal positions. In both men and women, BMI was strongly correlated with subcutaneous fat. However, BMI was weakly correlated with perirenal fat. CONCLUSIONS: Women exceed men in subcutaneous fat, while men exceed women in perirenal fat. Obese patients are very likely to have large amounts of subcutaneous fat, but will not necessarily have proportionally increased fat around their kidneys when compared to the patients with lower BMI. These differences may have important implications for surgical approaches to the kidney.

Premature ejaculation: bother and intravaginal ejaculatory latency time in Iran.

INTRODUCTION: Complaints of premature ejaculation (PE) and its repercussions are culture-dependent. AIM: To report the measured intravaginal ejaculatory latency time (IELT) and the impact of PE in Kermanshah, Iran. METHODS: From November 1996 through October 2008, 3,458 patients presented to us with self-diagnosed PE. In the first visit, after obtaining a psychosocial and sexual history, PE-specific bother was self-rated by the patients and the patients were advised to measure their IELTs over the next 2-3 weeks. In the second visit, the measured IELTs were reported by the patients. MAIN OUTCOME MEASURES: Patients' measured IELT and bother score. RESULTS: Age range was 17-80 years (mean 34.1, standard deviation [SD] 9.1, median 32). Sixty-five percent were married. Primary and secondary PE was reported by 2,105 (60.8%) and 1,353 (39.1%) patients, respectively. Occasional PE was reported by 36 (0.01%). Of those with multiple partners, 6% had partner-specific PE. IELT distribution was positively skewed. Anteportal ejaculation was reported by 97 (2.8%). In 3,458 self-reported PE patients, IELT was 1-15 seconds in 542 (15.7%), 16-30 seconds in 442 (12.8%), 31-60 seconds in 978 (28.3%), > 1 2 5 minutes in 136 (3.9%). IELTs of

Infant with concomitant presence of hernia/hydrocele and primary paratesticular neuroblastoma: a diagnostic and therapeutic challenge.

We report an 8-month-old boy with stage 1 neuroblastoma, whose "testicular tumor" was removed during a "radical orchiectomy" by a pediatric surgeon who encountered a scrotal mass during a hernia repair. Pathologic examination of the specimen suggested seminoma and the surgeon sent the patient for cisplatin-based chemotherapy. However, follow-up examination showed a normal testis. Reexamination of the specimen in other laboratories proved neuroblastoma. The patient is tumor free after 36 months of follow-up. This case shows that in presence of hernia, distorted anatomy, and inguinal testis, paratesticular tumors can be misdiagnosed for the testis and cause great diagnostic and therapeutic difficulty.

Sexual function and tunica albuginea wound healing following penile fracture: An 18-year follow-up study of 352 patients from Kermanshah, Iran.

INTRODUCTION: We present a study on the experiences of penile fracture in an Iranian population. Aim. To determine the long-term outcome of penile fracture. METHODS: Between April 1990 and May 2008, 373 patients presented with clinical features suggestive of penile fracture. Of these, 11 declined surgery. The remaining 362 were operated upon using a degloving incision. Ten patients had venous injury and 352 had penile fracture. At follow-up visits, in addition to answering our questionnaire, the patients completed the International Index of Erectile Function (IIEF), Erection Hardness Grading Scale (EHGS), and global self-assessment of potency (GSAP). To enhance documentation and to promote transparency, with the patients' permission, their full name and hospital chart number was sent to the journal. MAIN OUTCOME MEASURES: Clinical findings and IIEF and EHGS scores. RESULTS: Mean patients' age was 29.6 years. Mean duration of follow-up was 93.6 months. Diagnosis was solely clinical. At presentation, 278 (78.9%) reported no pain. Cavernosography, ultrasonography, or magnetic resonance imaging was not used in any of the patients. Penile fracture was due to taqaandan in 269 patients (76.4%). Patients were treated with surgical exploration and repair within 24 hours of admission, regardless of delay in presentation. A nodule was found at follow-up in 330 patients (93.7%). The painless, mostly proximal nodule was palpated at the floor of the corpora cavernosa, in a deep midline position above the corpus spongiosum. The non-expansive nodule was not associated with erectile dysfunction (ED) or Peyronie's disease. Postoperative complications included mild penile pain in cold weather (two patients), transient wound edema (one patient), mild chordee (four patients), and occasional instability of the erect penis (one patient). Postoperatively, of the 217 patients who had partners, 214 (98.6%) were potent. Mean IIEF ED domain score was 29.8 +/- 1.1. The EHGS score was 4 in 203 and 3 in 11. The GSAP score was 0 in 204, 1 in 8, and 2 in 2. ED in the remaining three could not be explained by penile fracture. Of 10 nonoperated patients, eight (80%) developed ED. CONCLUSION: Pain is rare in penile fracture. Postoperatively, almost all patients develop a permanent, inconsequential, fibrotic nodule. Our time-tested approach provided excellent long-term sexual function.

Male sexual dysfunction in unconsummated marriage: long-term outcome in 417 patients.

INTRODUCTION: Little research has been conducted about unconsummated marriage (UCM). AIM: To report the long-term outcome of male sexual dysfunction (MSD) in UCM. METHODS: From 1997 to 2008, 417 couples presented to the author with UCM. The mean UCM duration ranged from 1 hour to 8 years. The median follow-up was 78.5 months. MAIN OUTCOME MEASURES: Self-reported MSD in UCM based upon clinical history taking. RESULTS: In 177 cases, UCM was due to erectile dysfunction (ED) (86), premature ejaculation (PE) (89), performance anxiety (25), vaginismus (34), hypodesire disorder (6), not knowing the coital technique (8), men who have sex with men (MSM) (2), hypogonadism (1), request by bride to delay coitus (1), and thick hymen (1) (more than one factor involved in many cases). In the remaining 240 cases, UCM was due to being under social pressure to have a quick intercourse while relatives waited behind the door to confirm and celebrate coitus by checking a handkerchief that was placed beneath the bride to become bloody by hymen perforation. Intracavernosal injection (ICI) using papaverine +/- phentholamine was used in 239 cases (57.3%); 221 (92.4%) responded. The eight cases who did not know the coital technique responded to sex education. Of the 50 men who were prescribed phosphodiesterase type 5 inhibitors, only 4 responded. Of the 26 men who received clomipramine (21) or fluoxetine (5) for PE, 2 and 1 responded, respectively. Fourteen grooms who did not respond to treatments later consummated spontaneously. No treatment was given to 94 grooms, including men with a diagnosis of psychotic disorder, men with learning difficulties, divorcing patients, and men in obligatory, loveless marriages. Ten untreated patients later consummated spontaneously. Of the 260 patients who consummated either with treatment (236) or spontaneously (24), 58 (22.3%) later presented with sexual complaints. The remaining 202 did well at a follow-up. Of the 157 couples who did not respond to treatment or did not receive treatment, 62 were either divorced or divorcing. CONCLUSION: We strongly advise ICI as the first-line treatment of UCM. Oral therapies of ED and PE, vacuum constriction devices (VCD), and hymenectomy are of limited value. No treatment is indicated in many cases. Most grooms do well sexually in a long-term follow-up.

Sperm count and sperm motility in incidental high-grade varicocele.

One hundred twenty-four otherwise healthy men with suspected high-grade varicocele, comprised of 28 patients with grade 2 and 96 with grade 3 varicocele, were referred to us by their primary care providers to determine their exact grade so that they could be exempted from the compulsory armed force service if they had grade 3 varicocele. In the grade 2 and grade 3 groups, mean sperm concentration and mean sperm motility were 80.89 million per milliliter (SD, 38.98 million/mL; median, 74.5 million/mL; range, 22-210 million/mL) and 78.77 million per milliliter (SD, 41.34 million/mL; median, 77 million/mL; range, 0-223 million/mL) and 58.39% (SD, 13.7%; median, 60%; range, 22-75%) and 60.31% (SD, 16.93%; median 65%; range, 0-80%), respectively, with no statistically significant differences between the two groups, no patient with infertility as a complaint during a 20-month period, and no patient with sperm concentrations of <20 million/mL, but with six patients with sperm motilities <50%. In summary, by far the great majority of patients with high grade varicocele have more than normal sperm output. Higher grades of varicocele are not associated with more pronounced deleterious effects on sperm concentration and percentage motility. Incidentally diagnosed high-grade varicocele is not a progressive condition, and almost all patients retain normal semen quality, at least over a period of 20 months.

Trauma as the cause of Peyronie's disease: penile fracture as a model of trauma.

PURPOSE: This study was performed to determine whether patients with penile fracture or a long history of forcefully bending the erect penis (taqaandan), as models of acute and chronic penile trauma, had an increased rate of Peyronie's disease (PD). MATERIALS AND METHODS: The study included 193 surgical cases of penile fracture (average followup 85 months), 150 cases of long history of taqaandan, and 50 cases of PD. All 3 groups of patients were interviewed and physically examined. RESULTS: Signs of PD were found in only 1 case of long-term taqaandan and in no case of penile fracture. None of the 50 cases of PD had a history of penile fracture. CONCLUSIONS: Severe, acute trauma of penile fracture and moderate, chronic buckling injury of taqaandan are not associated with later development of PD. These findings question whether the hypothesis that trauma, trauma-induced smoldering inflammatory cascade and aberrant wound healing are the main causes of PD. Alternative, plausible, evidence based explanations should be sought for the etiology of PD. Any theory on the etiology of PD should provide an explanation for total lack of occurrence of PD following the trauma of penile fracture.

Tube-onlay-tube tunica vaginalis flap for proximal primary and reoperative adult hypospadias.

PURPOSE: We describe the surgical technique of and report the results in the first 20 patients who underwent combined onlay-tube construction of a tunica vaginalis flap. MATERIALS AND METHODS: We repaired 20 cases of proximal primary (8) and repeat (12), adult hypospadias using a tube-onlay in 4, an onlay-tube in 3, a tube-onlay-tube in 9 and an onlay-tube-onlay in 4. In 15 patients contralateral tunica vaginalis was used as a blanket wrap. Three to 6 months postoperatively after obtaining informed consent retrograde urethrography, cystourethroscopy, uroflowmetry and urethral biopsy were done in 20, 17, 10 and 13 patients, respectively. RESULTS: No fistula or diverticulum developed. Complications occurred in 3 patients (15%), including urethral stricture, meatal stenosis and urethral stricture, and meatal regression and urethral stricture in 1 each. All strictures occurred in the distal urethra in reoperative cases. At long-term followup there was no recurrent stricture or meatal stenosis after internal urethrotomy and dilation. Urethral biopsy in all 13 patients showed a stratified epithelium indistinguishable from native urethra. The reasons for delayed presentation include perceiving hypospadias as a normal variation (paribor or cut by angels), losing hope for a cure after multiple failed repairs, being told by urologists that repair is futile and pressure by wives for cosmetic or fertility reasons. CONCLUSIONS: The place of tunica vaginalis in hypospadias surgery is more than coverage for urethroplasty. It can be successfully used for substitution urethroplasty. As an extension to the principles of the onlay flap and the concept of urethral plate preservation, combined onlay-tube constructions of tunica vaginalis, including a tube-onlay-tube flap, are successfully applicable to proximal hypospadias, especially in reoperative cases. Urothelialization of the tunica vaginalis occurs within months of surgery.

Penile fracture in Kermanshah, Iran: the long-term results of surgical treatment.

OBJECTIVE: To determine the long-term outcome of the surgical management of penile fracture. PATIENT AND METHODS: In all, 170 patients (mean age 27 years, sd 13, median 24, range 13-80) with penile fracture undergoing surgery between April 1990 and December 2000 were reviewed. In addition to a history, physical examination and hospital records, long-term potency (> 6 months after surgery) was evaluated using the patients' self-rated assessment of erectile function and the International Index of Erectile Function (IIEF-5) questionnaire. The results were correlated with the surgical findings. A control group of 200 men also self-rated their erectile function and completed the IIEF-5. For those patients who presented with their partners, the partner's satisfaction with erections was also evaluated. The mean (median, range) follow-up after injury was 53 (61, 6-132) months. RESULTS: Satisfactory and painless erectile function with a soft straight penis was reported by 162 patients (95.2%). Complications occurred in eight patients (4.7%), of whom seven developed a mild (four) to moderate (three) penile curvature; five had penile nodules and four reported mild paresthesia over the scar line. Mild and moderate erectile dysfunction (ED) was reported by five and three patients, and four and five of controls, respectively (P > 0.05). There was no difference between the surgical findings of six patients with complications and those of the remaining 162. However, in the two remaining cases extensive injury was associated with moderate ED after surgery. Of eight patients with ED, seven responded to intracavernosal injection with papaverine/phentolamine. Erectile function returned within a mean (range) of 2 (1-5) days and coitus was possible approximately 2 weeks after the repair. Of the patients' partners, 94.1% reported satisfaction with erections and only one reported de novo dyspareunia. Penile fracture was not associated with an increased risk of ED (odds ratio 0.95; 95% confidence interval, 0.35-2.53). In sexually active participants, the mean (sd, range) IIEF-5 score for 162 patients was 23.2 (2.7, 13-25) and not significantly different from that for the 194 controls, at 22.8 (2.1, 11-25). However, patients had higher scores than controls for erectile firmness and maintenance ability (P < 0.05). CONCLUSIONS: Surgery for a fractured penis is safe and effective, restoring erectile function to that of controls. Surgical treatment is very satisfactory for patients and partners. Considering these encouraging results, surgical intervention is strongly recommended.