Reliability of prostate imaging reporting and data system version 2.1 for excluding clinically significant prostate cancer using a 1.5 tesla scanner.

INTRODUCTION: Multiparametric magnetic resonance imaging (mpMRI) of the prostate gland is now the recommended initial investigation of choice for the detection of Prostate cancer (PCa). It effectively identifies patients who require prostate biopsies due to the risk of clinically significant PCa. It helps patients with clinically insignificant PCa avoid the invasive biopsies and possible accompanying complications. Large clinical trials have investigated the accuracy of mpMRI in detecting PCa. We performed a local review to examine the reliability of omitting tissue sampling in men with a negative (PIRADS 2 (P2) or less) mpMRI in the primary diagnostic setting. METHODS: This was a retrospective study of patients with clinical suspicion of PCa within a 2-year period. Patients had a mpMRI prior to having trans-perineal prostate gland biopsies. Clinically significant disease was defined as Gleason 7 and above. The descriptive data was analysed using contingency table methods. A p-value less than 0.05 was statistically significant. RESULTS: Out of 700 patients 90 had an mpMRI score of PIRADS 2. Seventy-seven (85.5%) of these patients had a negative biopsy, 9(10%) showed Gleason 6, 4 patients showed Gleason 7 or above. 78 patients with PIRADS 2 had a PSA density of < 0.15, none of which had a clinically significant biopsy result. The negative predictive value of mpMRI from this study is 95%. CONCLUSION: Our results are in line with negative predictive values demonstrated in the current literature. This local study, likely applicable to other district general hospitals, shows that mpMRI is a safe and reliable initial investigation to aid decisions on which patients require biopsies.

Improving bone health in prostate cancer patients starting androgen deprivation therapy: does Fracture Risk Assessment Tool (FRAX®) enhance stratification and targeted management?

Androgen deprivation therapy for prostate cancer can lead to osteoporosis and increased fracture risk. The Fracture Risk Assessment Tool (FRAX®) questionnaire can be used for risk stratification, and our study has demonstrated that the majority of men (91%) in our cohort commencing ADT for prostate cancer were considered low risk for future osteoporotic fracture. PURPOSE/INTRODUCTION: Long-term use of androgen deprivation therapy (ADT) in prostate cancer patients results in increased bone turnover and decreased bone mineral density (BMD). Proper assessment of any existing osteoporotic fracture risk is crucial prior to starting treatment. However, this risk assessment is poorly performed in these patients in spite of available validated tools including the Fracture Risk Assessment Tool (FRAX®). The objective of this study was to assess the distribution of osteoporotic fracture risk in a cohort of men commencing ADT for prostate cancer using the FRAX® algorithm. METHODS: Between July 2020 and May 2022, 200 men filled in the FRAX® questionnaire just before ADT. They were stratified into the high-risk (> 20% probability of a MOF over the next 10 years), intermediate-, and low-risk categories for fragility fractures. We also measured their serum vitamin D and calcium levels. RESULTS: The average age was 73.5 years (54-89). It took less than 10 min to complete the assessment. Only six patients were at high-risk, were started on bisphosphonates immediately, and referred for a dual energy X-ray absorptiometry (DEXA) scan. Twelve patients in the intermediate-risk category were referred for DEXA scans for bone mineral density measurements. A total of 182 patients (91%), were in the low-risk category and given lifestyle advice only. All had normal calcium levels but 134 (67%) patients, mostly in the low-risk category, had reduced vitamin D levels (< 50 nmol/L). CONCLUSION: The FRAX® questionnaire is simple and immediately identifies patients who are at risk of fragility fractures. Our study has demonstrated that the majority of men (91%) in our cohort commencing ADT for prostate cancer were considered low risk for future osteoporotic fracture. We were surprised that more than half of our patients had low vitamin D levels.

Family structure and substance use in 6,178 American Indian youth: a cross-sectional study.

OBJECTIVE: Adolescents from single-parent families are at significantly higher risk of substance use compared to those from mother-father families. More than half of American Indian (AI) children live in single-parent families, the second highest percentage among all groups. Given the paucity of research pertaining to the role of family structure and substance use in the AI population, we sought to examine this relationship. MATERIALS AND METHODS: Data from this study were obtained from the Substance Use Among American Indian Youth: Epidemiology and Etiology, [US], 2015-2020 study. Response variables of interest included age at first substance use, number of substances used, ever-use of substance, and substance use type (i.e., alcohol, cigarette, marijuana, etc.). RESULTS: Living in a father-only or mother-only setting showed a similar pattern of drug use. There was a significant increase in the risk of cigarette, alcohol and marijuana use. For cigarettes, the odds ratio was (OR = 2.60, 95% CI 1.80-3.75) in father-only setting compared to (OR = 1.42, 95% CI 1.13-1.78) for mother only setting. Alcohol use showed (OR = 1.72, 95% CI 1.19-2.50 and OR = 1.40, 95% CI 1.12-1.74) for father-only and mother-only respectively and marijuana use showed (OR = 1.59, 95% CI 1.10-2.30 and OR = 1.54, 95% CI -1.24-1.92) for father-only and mother-only respectively. CONCLUSIONS: Disturbed family structure is associated with increased risk of substance use among AI youth. This indicates the importance and need for policy and community level interventions to reduce youth substance exposure.

Early administration of phosphodiesterase 5 inhibitors after induction of diabetes in a rat model may prevent erectile dysfunction.

BACKGROUND: The possible role of phosphodiesterase 5 inhibitors (PDE5Is) in prevention of negative effect of diabetes mellitus (DM) on erectile function is not well settled. OBJECTIVES: To investigate the effect of early administration of vardenafil on erectile function, cavernosal structure, and genes expression in a rat model of DM. MATERIALS AND METHODS: This experimental study was carried out at Suez Canal University's research laboratory. This study was conducted on a total of 60 adult male Albino Wistar rats, aged 60-80 days and weighing an average of 200 g. Rats were equally divided into six groups of 10 rats each: Group I (sham); Group II (DM with no treatment); Groups III, IV, V, and VI received vardenafil started at day 1, week 4, week 8, and week 12 after induction of DM, respectively. Functional study assessment of all groups was performed before euthanization, and then tissues were harvested for histopathological, ultrastructural, and molecular examinations. RESULTS: There was a significant difference of intracavernosal pressure between early (94 ± 2.18) and late (40.5 ± 1.94) treatment groups (p = 0.011). Histopathological and ultrastructural changes of DM with no treatment and late treatment groups showed distorted cavernous architecture and extensive fibrosis. There was significant difference of smooth muscle to collagen ratio between early and late treatment groups (p = 0.035). There was significant upregulation of nNOS(p = 0.021) and iNOS (p = 0.047) in early vs. late treatment group. The difference was insignificant in eNOS (p = 0.386) or TGF-ß1(p = 0.149). DISCUSSION AND CONCLUSION: Early treated rats with vardenafil had preserved erection and normal cavernosal structure, ultrastructure and gene expression of iNOS, nNOS, eNOS, and TGF-ß1. Quantification of gene expression would improve our knowledge regarding cytokines expression and molecular background of DM-associated ED. Clinical application of this result may encourage early administration of PDE5I to prevent deleterious effects of DM on erectile function in newly diagnosed DM patients with probable uncontrolled blood glucose.

Association between leukocytospermia and semen interleukin-6 and tumor necrosis factor-alpha in infertile men.

Seminal cytokines were previously reported to adversely affect process of spermatogenesis and ultimately induce poor semen quality. However, association between both IL-6 and TNF-α and leukocytospermia was not yet settled. The aim of this study was to evaluate the association between leukocytospermia and levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in semen of infertile men. This cross-sectional study included 100 age-matched (≥18-45 years.) men. Participants were divided into four groups with 25 patients in each group: Group (A) - infertile patients with leukocytospermia and normal other semen parameters; Group (B) - infertile patients with leukocytospermia and abnormal semen parameters; Group (C) - infertile patients with oligospermia and/or asthenospermia and/or teratospermia but with no leukocytospermia; Group (D) - fertile patients with normal semen parameters and without leukocytospermia. All patients were assessed by detailed medical, sexual, fertility history, and complete physical examination. Laboratory assessment included hormonal and semen analysis and assessment of IL-6 and TNF-α in semen plasma. There were significant differences among the study groups regarding total sperm count, sperm concentration, and progressive motility (p < 0.05 for each). There was significant increase in semen WBC counts in groups A and B vs. groups C and D (p = 0.003). There were significant associations between increase levels of WBCs ≥ 5/HPF and decrease levels of total sperm count (p = 0.023), sperm concentration (p = 0.001), and sperm progressive motility (p = 0.02). There were significant upregulations in mean level of IL-6 (p = 0.001) and mean level of TNF-α (p = 0.003) in groups A and B vs. groups C and D. Overall, leukocytospermia is associated with reduction in sperm count, progressive motility and further upregulation of seminal IL-6 and TNF-α. The effect of treatment of leukocytospermia on the level of seminal cytokines is important point of future research.

Testosterone level and endothelial dysfunction in patients with vasculogenic erectile dysfunction.

The association between endothelial dysfunction and late onset hypogonadism (LOH) in patients with vasculogenic erectile dysfunction (ED) is not yet well settled. Our objective was to assess the association between LOH and endothelial dysfunction in patients with vasculogenic ED. Throughout 2014-2015 a total of 90 men were enrolled in this cross-sectional observational study. Of them 60 patients with a clinical diagnosis of ED were further subdivided into two equal groups: patients with vasculogenic ED and LOH (A); patients with vasculogenic ED and euogonadal (B). Thirty age-matched men with no ED or hypogonadism were enrolled as control group (C). All patients were subjected to detailed medical and sexual history, total testosterone (TT), calculated free (FT) and bioavailable testosterone (BT), flow cytometric evaluation for endothelial progenitor cells (EPCs) (CD45negative/CD34positive/CD144positive) and endothelial microparticles (EMPs) (CD45negative/CD144positive/annexin V positive). The mean age ± SD of the three groups A, B and C were 51.3 ± 11.1, 53.6 ± 10.6 and 48.3 ± 5 years, respectively, with insignificant age differences (p = 0.089). The diagnostic criteria of LOH were adapted according to European male aging study, 2010. The means of TT(ng/mL) were 2.32 ± 0.21, 6.43 ± 0.36 and 5.37 ± 0.30 in groups A, B and C, respectively. There were highly significant differences between group A and groups B and C (p < 0.001 for each). The means of EPCs were 0.43 ± 0.070, 0.22 ± 0.05 and 0.032 ± 0.013 in groups A, B and C, respectively. The means of EMPs were 0.15 ± 0.029, 0.056 ±  .013 and 0.014 ± 0.002 in groups A, B and C, respectively. There were significant differences between group C and groups A and B (p < 0.05 for each). This study clearly demonstrated that there is a significant association between LOH and the higher expression of EPCs and EMPs in patients with vasculogenic ED.

What is the current role of intracavernosal injection in management of erectile dysfunction?

The emerging of intracavernosal injection (ICI) of vasoactive materials was a major breakthrough in the treatment of erectile dysfunction (ED). However, the current state and future direction of ICI role in the armamentarium of diagnosis, prevention and treatment of ED are not well defined. The aim of this study was to address the current place of ICI in the armamentarium of ED diagnosis and treatment. An English-language MEDLINE review for the utilization of 'intracavernosal injection & erectile dysfunction' was performed from 1990 to present time. Four hundred forty-eight articles were analyzed and classified according to the current utilization of ICI in the following conditions; diagnosis of ED, phosphodiesterase-5 inhibitor (PDE5I) non-responders, diabetes, post radical prostatectomy (RP), stem cells and gene therapy, new intracavernosal drugs, adverse effects and couple satisfaction. This paper is not a standard systematic review; it is eventually a literature review of original peer-reviewed manuscripts and clinical trials reported in Medline. The comprehensive analyses of all the reviewed data were not possible as the level of evidence for utility of ICI in each topic was not available. Current date have established the role of ICI of vasoactive materials as a very common alternative domain in treatment of severe ED particularly in diabetic patients, post-RP, PDE5I non-responders. Further, new studies have denoted the potential future role of intracavernosal treatment for ED in the era of stem cells and gene therapy. ICI of vasoactive material continues to be a highly effective and safe treatment tool for men with wide varieties of ED etiologies. Several experimental and clinical studies are currently investigating new ICI materials. Hopefully in the near future, we might witness evolved molecules and innovative strategies that could help to treat ED patients with different etiologies.

Sildenafil for erectile dysfunction in the Middle East: observational analysis of patients with diabetes and/or hypertension treated in the clinical practice setting.

The effectiveness and tolerability of 12 weeks of open-label treatment with sildenafil citrate for erectile dysfunction (ED) associated with a diagnosis of diabetes mellitus and/or hypertension were assessed in clinical practice in three Middle Eastern countries. The dose was initially 50 mg and was adjusted by the physician as needed (permissible dose range 25 - 100 mg). Total mean ± SD score on the five-item version of the International Index of Erectile Function (severe ED, score 0 - 7; no ED, score 22 - 25) was 13.6 ± 5.7 at baseline (4556 patients) and increased significantly to 21.7 ± 4.1 at week 12. Global effectiveness was rated as good or very good by 91.4% of patients, 93.9% rating their sexual activity as spontaneous and 91.4% as natural. Discontinuation of sildenafil due to adverse events was infrequent (0.5%). Tolerability was rated as good or very good by 95.7% of patients. It is concluded that sildenafil was a well-tolerated and highly effective treatment of ED in outpatients with diabetes and/or hypertension from the three Middle Eastern countries studied.

Cardiovascular diseases and erectile dysfunction: the two faces of the coin of androgen deficiency.

Traditionally, clinical conditions synonymous with the ageing male included cardiovascular disease (CVD), type 2 diabetes mellitus (DM) and sexual dysfunction, and were widely regarded as independent clinical entities. Over the last decade, interrelationship of clinical conditions has been convincingly demonstrated. Declining testosterone levels in the elderly, once regarded as an academic endocrinological question, appear to be central to the listed pathologies. It is now clear that erectile dysfunction is an expression of endothelial dysfunction. Testosterone deficiency is associated with an increased incidence of CVD and DM. The latter is often the sequel of the metabolic syndrome. Visceral obesity, a pivotal characteristic of the metabolic syndrome, suppresses the hypothalamic-pituitary-testicular axis leading to diminished testosterone production. Conversely, substantial androgen deficiency leads to signs and symptoms of metabolic syndrome. It is erroneous not to include testosterone measurements in the progress of the CVD, DM and erectile dysfunction. These conditions correlate strongly with testosterone deficiency.

Type 2 diabetes-associated androgen alteration in patients with erectile dysfunction.

Our objective was to assess the pattern of type-2 diabetes-associated androgen alteration in patients with erectile dysfunction (ED). A total of 127 diabetic male patients with ED were enrolled in this study. Erectile function was assessed using the International Index of Erectile Function (IIEF). At the time of assessment, patients were also interviewed and assessed for socio-demographic and medical history that includes duration and severity of diabetes mellitus (DM). Patients underwent routine laboratory investigations, in addition to total testosterone (T), dehydroepiandrosterone sulphate (DHEA-S) and insulin assessment. The mean age +/- SD was 53.8 +/- 9.3 years. Of patients 25.2% (n = 32/127), 6.3% (n = 8/127) and 31.5% (n = 40/127) had low total T, low DHEA-S and hyperinsulinaemia respectively. There were significant association between the increase in age and body mass index and the presence of low T level. Of the patients 37.5% (n = 12/32) with low T level had glycosylated haemoglobin (HbA1c) >7% while, 22.1% (n = 21/95) of the patients with normal T level had HbA1c >7% (p < 0.05). There were significant associations between the number of patients with low level of total T or DHEA-S and poor control of DM. Patients with low T level were two times more likely (56.3%, n = 18/32) to have severe ED than patients with normal T level (27.4%, n = 26/95) (p < 0.01). There were significant differences between the mean levels of total T or DHEA-S and poor control of DM. No significant associations were detected between hyperinsulinaemia and the level of fasting blood sugar, duration of DM, metabolic control of DM or ED severity. Patients with low T level were three times as likely to have hyperinsulinaemia as those patients with normal T level (p < 0.05). The current study clearly demonstrated that there were significant associations between low level of total T or DHEA-S and poor control of DM.

Intracavernosal prostaglandin E1 self vs office injection therapy in patients with erectile dysfunction.

We have investigated the reliability of intracavernosal prostaglandin E1 (PGE1) office vs self-injection therapy in patients with erectile dysfunction (ED). A total of 298 male patients with ED were enrolled in this study. In all patients, intracavernosal titration of the PGE1 dose was performed. A total of 106 patients were enrolled in the self-injection program, and 192 patients were enrolled in the office injection program. There were significant differences between number of injections and amount of PGE1 per month, total number of injections, and total amount of PGE1 on office and self-injection programs (P < 0.05 for each). There was a significant increase in the dropout rate in the office injection group compared with the self-injection group (P < 0.05). There was an increase in penile fibrosis in the self-injection program compared with the office program (P < 0.05). A self-injection program is reliable. Office injection program can be reserved for a subset of ED patients with special preferences.

Characteristics of erectile dysfunction in Saudi patients.

We investigated the characteristics of erectile dysfunction (ED) in ambulatory Saudi patients. A total of 680 male patients were assessed for ED using IIEF. Patients were also interviewed for sociodemographic data, medical history and risk factors for ED. Assessment for penile vasculature using color Doppler ultrasonography and rigidometer was performed. In all, 21.4% of the patients with severe ED were <50 y and 78.6% of them were > or =50 y (P<0.001). Of the patients, 20% had psychogenic, while 80% had organic causes of ED. Of the patients, 10% had mild, 39.3% had moderate and 50.7% had severe ED. There was a significant association between increasing severity of ED and the presence of diabetes, hypertension, dyslipidemia, smoking, increased BMI, increased values of EDV, decreased values of PSV, RI and rigidometer (P<0.001 for each). Moderate to severe ED is common among Saudi patients. This study provides a quantitative estimate of the characteristics of ED in ambulatory Saudi patients.

Association between International Index of Erectile Function and axial penile rigidity in patients with erectile dysfunction.

We investigated the association between the International Index of Erectile Function (IIEF) and axial penile rigidity parameters in patients with erectile dysfunction (ED). A total of 516 male patients (491 patients with ED and 25 patients without ED) were assessed using IIEF. Patients were assessed for axial penile rigidity (APR) using a digital inflection rigidometer. Mean age+/-s.d. was 52.4+/-9.9 y. ED was mild in 11.4% of the patients, moderate in 40.1%, and severe in 48.5%. Regarding APR, the following was found: (1) no significant difference between patients who had a mild degree of ED and patients who had no ED (P>0.05); (2) a significant difference between patients with different degrees of ED (P<0.05 for each); (3) a significant association between overall presence of ED and low APR (P<0.05). IIEF score is associated with APR and can differentiate between patients with and without ED.

Traumatic arteriogenic erectile dysfunction: a rat model.

We developed a rat model of traumatic arteriogenic erectile dysfunction (ED) for the study of vasculogenic ED. Bilateral ligation of the internal iliac artery was performed on 30 three-month old male Sprague-Dawley rats as an experimental group. The control group consisted of 12 rats which underwent dissection of the internal iliac artery without ligation. Before their euthanization at 3 days, 7 days, and 1 month (10 rats in the experimental group and four rats in the control group at each time point), erectile function was assessed by electrostimulation of the cavernous nerves. Penile tissues were collected for nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase staining, trichrome staining, electron microscopy and RT-PCR for transforming growth factor beta (TGF-beta1), insulin like growth factor-I (IGF-I) and fibroblast growth factors (FGF) mRNA expression. Electrostimulation of the cavernous nerves revealed a highly significant declining of the intracavernous pressure after 3 and 7 days. No significant recovery of erectile function was noted at 1 month. Histology showed degeneration of the dorsal nerve fibers in all experimental rats. There was little decrease in the bulk of intracavernous smooth muscle in the experimental rats euthanazed 7 and 30 days. NADPH diaphorase staining revealed a significant decrease in nitric oxide synthase (NOS) containing nerve fibers in the dorsal and intracavernosal nerves in all rats in the experimental group. Electron microscopy showed a variety of changes such as collapse of sinusoids, increased cell debris, fibroblast and myofibroblast loss, intracellular deposition of fat and collagen and fatty degeneration. RT-PCR revealed up-regulation of TGF-beta1 after 3 days but not after 7 days or 1 month. There is no significant difference in IGF-I or FGF expression between the experimental and control group. Bilateral ligation of internal iliac arteries produces a reliable animal model for traumatic arteriogenic ED. Further studies are needed to investigate the molecular mechanism of ED in this model.

Effect of a Chinese herbal medicine mixture on a rat model of hypercholesterolemic erectile dysfunction.

PURPOSE: We examine the effect of a Chinese herbal medicine mixture on erectile function in a rat model of hypercholesterolemic erectile dysfunction. MATERIALS AND METHODS: In this study 32, 3-month-old Sprague-Dawley rats were used. The 8 control animals were fed a normal diet and the remaining 24 were fed 1% cholesterol diet for 4 months. After 2 months herbal medicine was added to the drinking water of the treatment group of 16 rats but not the cholesterol only group of 8. Of the 16 rats 8 received 25 mg./kg. per day (group 1) and 8 received 50 mg./kg. per day (group 2) of Chinese herbal medicine mixture. Serum cholesterol levels were measured at 2 and 4 months. At 4 months erectile function was evaluated with cavernous nerve electrostimulation in all animals. Penile tissues were collected for electron microscopy, and to perform Western blot for endothelial nitric oxide synthase, neuronal nitric oxide synthase, basic fibroblast growth factor (bFGF) and caveolin-1. RESULTS: Serum cholesterol levels were significantly higher in animals fed the 1% cholesterol diet compared to controls at 2 and 4 months. Nevertheless, there was no significant difference among group 1 (145 +/- 30 mg./dl.), group 2 (157 +/- 20) and the cholesterol only group (143 +/- 15). Systemic arterial pressure was not significantly different between the animals that were fed the 1% cholesterol diet and the controls. During electrostimulation of the cavernous nerve peak sustained intracavernous pressure was significantly lower in the cholesterol only group (50 +/- 23 cm. H2O) compared to the control group. Conversely erectile function was not impaired in the herbal medicine treated rats. Electron microscopy showed many caveolae with fingerlike processes in the cavernous smooth muscle and endothelial cell membranes in control and treated rats but not in the cholesterol only group of rats. Western blot did not show a difference among groups in protein expression for endothelial nitric oxide synthase and neuronal nitric oxide synthase in penile tissue but caveolin-1 and bFGF protein expression was significantly higher in groups 1 and 2 than in the cholesterol only and control groups. CONCLUSIONS: Rats developed erectile dysfunction after being fed a 1% cholesterol diet for 4 months. Although serum cholesterol levels were similar in the cholesterol only rats and those treated with Chinese herbal medicine mixture, erectile response was significantly better in the treated group. The mechanism of the herbal medicine is unknown. High levels of bFGF and caveolin-1 expression in the treated group may protect the cavernous smooth muscle and endothelial cells from the harmful effect of high serum cholesterol.

Microsatellite alterations and loss of heterozygosity in Peyronie's disease.

PURPOSE: In the present study, we tested the hypothesis that microsatellite alterations (MSI) and loss of heterozygosity (LOH) are associated with Peyronie's disease. To test this hypothesis, we analyzed samples from patients with Peyronie's for MSI and LOH on chromosomes 3, 8 and 9 using 20 different genetic markers. MATERIALS AND METHODS: DNA was isolated from the penile fibrotic plaque, amplified using PCR, and analyzed for MSI and LOH on chromosomes 3, 8 and 9 using 20 different polymorphic markers (D3S1228, D3S1298, D3S1560, D3S1745, D3S2396, D3S647, D8S133, D8S255, D8S259, D8S260, D8S262, D8S285, D8S298, D8S507, D8S528, D9S162, D9S171, D9S1747, D9S1748, and D9S273). Only 10 primers (D3S1560, D3S647, D3S1298, D8S262, D8S260, D8S528, D9S171, D9S1747, D9S273 and D9S1748) showed MSI and LOH in Peyronie's samples. Microsatellite alterations and LOH were analyzed by a PCR-based technique developed in our laboratory. RESULTS: This study demonstrates a high frequency of MSI and LOH in Peyronie's disease. Fourteen of 35 cases (40%) showed MSI at a minimum of one locus, 6 of 35 cases (17%) at a minimum of 2 loci and three of 35 (8.5%) cases at three or more loci. D9S273 locus showed highest MSI when compared with other loci examined in this study. For LOH, 14 of 35 cases (40%) were observed at a minimum of one locus, 5 of 35 cases (14%) at minimum of two loci and one out of 35 cases (2.8%) showed LOH at three or more loci. The D3S1560 and D9S171 loci showed highest LOH when compared with all other loci examined in this study. CONCLUSION: This is the first report demonstrating that a high frequency of MSI and LOH is associated with Peyronie's disease, suggesting their role in the pathogenesis of this disease.

Mesenchymal reprogramming of adult human epithelial differentiation.

The objective of this study was to determine whether neonatal rat seminal vesicle mesenchyme (rSVM) can reprogram epithelial differentiation in a fully differentiated adult human bladder epithelium. For this purpose neonatal rSVM was isolated from newborn (0-day) Sprague-Dawley rats, and normal adult human bladder epithelium (hBLE) was isolated from radical cystoprostatectomy specimens to prepare rSVM+hBLE tissue recombinants in vitro. After overnight culture the tissue recombinants were grafted beneath the renal capsule of male athymic rodent hosts and allowed to grow in vivo for 6 months. As controls, rSVM and hBLE were grafted separately and allowed to grow for the same period. Tissue recombinants and control tissue grafts were harvested, and secretions were collected for biochemical studies. Tissues were fixed both for histologic as well as immunohistochemical staining. Neonatal rSVM induced normal adult human bladder urothelium to form glandular structures resembling prostate. The induced prostatic acini were filled with secretions that expressed human prostate-specific secretory proteins. These findings demonstrate that adult human urothelial cells retain a responsiveness to neonatal prostatic mesenchymal inductors. Change in urothelial histodifferentiation was associated with change in functional activity. The ability of the neonatal rat mesenchymal tissues to induce morphologic as well as biochemical changes in normal adult human urothelium provides a basis for human tissue engineering and organ reconstruction.

Effects of diabetes on nitric oxide synthase and growth factor genes and protein expression in an animal model.

Erectile dysfunction occurs frequently in humans with diabetes mellitus; the molecular basis of this phenomenon is not known. We investigated the effects of diabetes on penile erection, nitric oxide synthase and growth factors expression in an animal model. Forty male rats were divided into two groups: the experimental group (n = 30) received intraperitoneal injection of Streptozotocin (STZ) dissolved in citrate buffer to induce diabetes; ten age-matched control rats received injection of citrate buffer vehicle only. Before euthanization at eight weeks, erectile function was assessed by electrostimulation of the cavernous nerves. NADPH diaphorase staining was used to identify NOS and immunostaining technique was used to identify nNOS in the penile nerve fibers. RT-PCR was used to identify mRNA expression of nNOS, eNOS, iNOS, ER-beta, ER-alpha, NGF, IGF-I, TGF-beta 1, and AR. Western blot was used to identify nNOS, IGF-I, NGF, and TFG-beta protein expressions. In the diabetic group, there was: (1) a significant decrease in NOS containing nerve fibers in the dorsal and intracavernosal nerves; (2) a significant lower maximal intracavernosal pressure. RT-PCR showed down-regulation of nNOS (large form), iNOS and ER-beta mRNA expression, Immunoblot showed down-regulation of nNOS protein expression and nNOS immunostaining showed less positive staining in the dorsal and intracavernous nerves in the diabetic group. These molecular changes may provide the basis for further studies to explore the association between diabetes and impotence.

The effects of colchicine on a Peyronie's-like condition in an animal model.

PURPOSE: We have developed an animal model of Peyronie's disease by injecting transforming growth factor beta (TGF-beta) into the rat penis. Our objective is to study the effects of colchicine on the Peyronie's condition in an animal model. MATERIALS AND METHODS: Thirty-six adult male Sprague-Dawley rats received TGF-beta injections into the tunica albuginea and were divided into two groups (n = 18 each). Rats in the first group were divided into three subgroups (n = 6 each). Each rat in the three subgroups received the following: Subgroup 1 received colchicine, subgroup 2 received ibuprofen, and subgroup 3 received regular water. The rats were euthanized after 6 weeks. Rats in the second group were also divided into three subgroups. These rats received the same treatments as the rats in the first group, but treatments began 6 weeks after TGF-beta injection. These rats were euthanized after 12 weeks. Tunical tissue samples were collected and examined using Hart and trichrome stains, electron microscopy (EM), and western blot analysis for TGF-beta detection. RESULTS: In the first group, the colchicine-treated rats exhibited less collagen deposition and less elastic fiber fragmentation than the untreated or ibuprofen-treated rats. EM confirmed the results and showed normal distribution and shape of both collagen and elastic fibers in the colchicine-treated group. In the second group, the colchicine-treated rats exhibited less crowding of the collagen fibers. However, the elastic fibers remained fragmented and scarce. Western blot analysis showed significant down-regulation of TGF-beta expression (5/6) in the colchicine-treated group after 6 weeks. Down-regulation was observed in only 1/6 in both ibuprofen and non-treated groups. After 12 weeks 2/6, 1/6, and 1/6 rats displayed down regulation in the colchicine treated, ibuprofen treated, and non-treated groups, respectively. CONCLUSION: Early colchicine treatment may suppress a Peyronie's like condition in the rat animal model.