The FGF/FGFR system in the physiopathology of the prostate gland.

Fibroblast growth factors (FGFs) are a family of proteins possessing paracrine, autocrine, or endocrine functions in a variety of biological processes, including embryonic development, angiogenesis, tissue homeostasis, wound repair, and cancer. Canonical FGFs bind and activate tyrosine kinase FGF receptors (FGFRs), triggering intracellular signaling cascades that mediate their biological activity. Experimental evidence indicates that FGFs play a complex role in the physiopathology of the prostate gland that ranges from essential functions during embryonic development to modulation of neoplastic transformation. The use of ligand- and receptor-deleted mouse models has highlighted the requirement for FGF signaling in the normal development of the prostate gland. In adult prostate, the maintenance of a functional FGF/FGFR signaling axis is critical for organ homeostasis and function, as its disruption leads to prostate hyperplasia and may contribute to cancer progression and metastatic dissemination. Dissection of the molecular landscape modulated by the FGF family will facilitate ongoing translational efforts directed toward prostate cancer therapy.

Estrogens in Male Physiology.

Estrogens have historically been associated with female reproduction, but work over the last two decades established that estrogens and their main nuclear receptors (ESR1 and ESR2) and G protein-coupled estrogen receptor (GPER) also regulate male reproductive and nonreproductive organs. 17ß-Estradiol (E2) is measureable in blood of men and males of other species, but in rete testis fluids, E2 reaches concentrations normally found only in females and in some species nanomolar concentrations of estrone sulfate are found in semen. Aromatase, which converts androgens to estrogens, is expressed in Leydig cells, seminiferous epithelium, and other male organs. Early studies showed E2 binding in numerous male tissues, and ESR1 and ESR2 each show unique distributions and actions in males. Exogenous estrogen treatment produced male reproductive pathologies in laboratory animals and men, especially during development, and studies with transgenic mice with compromised estrogen signaling demonstrated an E2 role in normal male physiology. Efferent ductules and epididymal functions are dependent on estrogen signaling through ESR1, whose loss impaired ion transport and water reabsorption, resulting in abnormal sperm. Loss of ESR1 or aromatase also produces effects on nonreproductive targets such as brain, adipose, skeletal muscle, bone, cardiovascular, and immune tissues. Expression of GPER is extensive in male tracts, suggesting a possible role for E2 signaling through this receptor in male reproduction. Recent evidence also indicates that membrane ESR1 has critical roles in male reproduction. Thus estrogens are important physiological regulators in males, and future studies may reveal additional roles for estrogen signaling in various target tissues.

Beneficial effects of lipidic extracts of saladette tomato pomace and Serenoa repens on prostate and bladder health in obese male Wistar rats.

BACKGROUND: Obesity is associated with increased risk of a number of serious medical conditions, including urological disorders. This study investigated the effect of lipidic extracts of saladette tomato pomace (STP) and Serenoa repens (SR) on the prostate and bladder in a rat obese model induced by high-carbohydrate diet. RESULTS: High-sucrose-fed rats showed higher prostate weight as well as increased contractility and stromal and epithelial hyperplasia in the prostate. Treatment with STP and SR improved contractility and diminished hyperplasia and hypertrophy in the prostate. Obese animals also showed impaired bladder contractility, but neither extract reversed this deterioration. In the histological study, a disarray in the process of smooth muscle cell proliferation with non-parallel fibers was observed; interestingly, treatment with STP and SR led to improvement in this derangement. CONCLUSION: These findings indicated impaired contractility and hyperplasia in the prostate and bladder of obese rats induced by high sucrose. STP and SR could enhance prostate function by reducing contractility and hyperplasia and improve smooth muscle fiber structure and decrease cell proliferation in the bladder, suggesting their possible health-beneficial effects on lower urinary tract symptoms. © 2017 Society of Chemical Industry.

Does MRI help in the pre - operative evaluation of pelvic fracture urethral distraction defect? - A pilot study.

OBJECTIVES: To study the usefulness of MRI in preoperative evaluation of PFUDD. Can MRI provide additional information on urethral distraction defect (UDD) and cause of erectile dysfunction (ED)? MATERIALS AND METHODS: In this prospective study, consecutive male patients presenting with PFUDD were included from Feb 2011 till Dec 2012. Those with traumatic spinal cord injury and pre-existing ED were excluded. Patients were assessed using IIEF questionnaire, retrograde urethrogram and micturating cystourethrogram (RGU+MCU) and MRI pelvis. Primary end point was erectile function and secondary end point was surgical outcome. RESULTS: Twenty patients were included in this study. Fourteen patients (70%) were ≤40years; fifteen patients (75%) had ED, seven patients (35%) had severe ED. MRI findings associated with ED were longer median UDD (23mm vs. 15mm, p=0.07), cavernosal injury (100%, p=0.53), rectal injury (100%, p=0.53), retropubic scarring (60%, p=0.62) and prostatic displacement (60%, p=0.99). Twelve patients (60%) had a good surgical outcome, five (25%) had an acceptable outcome, three (15%) had a poor outcome. Poor surgical outcome was associated with rectal injury (66.7%, p=0.08), cavernosal injury (25%, p=0.19), retropubic scarring (18.1%, p=0.99) and prostatic displacement (16.7%, p=0.99). Five patients with normal erections had good surgical outcome. Three patients with ED had poor outcome (20%, p=0.20). CONCLUSIONS: MRI did not offer significant advantage over MCU in the subgroup of men with normal erections. Cavernosal injury noted on MRI strongly correlated with ED. Role of MRI may be limited to the subgroup with ED or an inconclusive MCU.

[Results of a multicenter non-interventional study on the efficacy and safety of NeyroDoz complex for sexual dysfunction in men].

The article presents the results of a multi-center observational study carried out in 2014-2015 comprising 630 male patients from 23 Russian health care institutions. The study aimed to accumulate epidemiological data on sexual dysfunction in men and test the efficacy and safety of biologically active complex NeyroDoz. Data for the study were collected using questionnaires. The study findings showed a high prevalence of premature ejaculation (PE) in 38.2% of patients with chronic prostatitis (CP) and in 33.25% of patients with erectile dysfunction (ED). The data were analyzed for the total study population (n=630) and separately for three groups of patients selected according to the presence of PE (n=582), orgasmic disorders without PE (n=17) and increased anxiety related to urological diseases without PE (n=31). In all patients of the study, NeyroDoz intake produced a statistically significant increase in the intensity of orgasm from 5,0+/-2,2 to 7,6+/-1,8 points, duration of sexual intercourse from 3,3+/-5,4 to 6,5+/-4,8 min, and satisfaction with sexual intercourse from 1,4+/-0,7 to 3,1+/-1,1 points. In 81% of PE patients the duration of penetration phase of sexual intercourse increased by 50% of the baseline values. The intensity of orgasm increased on average by 60% and 75% in men with PE and orgasm disorders without PE, respectively. Reduction of psycho-emotional burden was observed in 90% of patients with anxiety and depression. The dietary supplement NeyroDoz showed clinical efficacy and safety in the combined treatment of sexual dysfunction in men.

[Experience of the use of drug urorec: efficacy and safety].

The article presents the experience of use of the new superselective alpha-blocker urorec (silodosin) in the treatment of 30 patients with lower urinary tract symptoms aged 49 to 69 years. Patients have received silodosin 1 capsule a day for 2 months. According to the results of study, silodosin has demonstrated high efficacy and an acceptable safety profile. It was shown that silodosin does not increase the risk of hypotension in patients taking antihypertensive medications. Therapy with silodosin had positive and statistically significant impact on subjective and objective symptoms of the disease, which was confirmed by the IPSS-QoL score and uroflowmetry. Silodosin has rapid onset of effect (3-4 days after the start of treatment); it can be used in all patients suffering from BPH and having indications to the administration of alpha-blockers, and does not require correction of doses of antihypertensive drugs in the case of combined appointment.

Semen quality and associated reproductive indicators in middle-aged males: the role of non-malignant prostate conditions and genital tract inflammation.

PURPOSE: To compare the associations between non-malignant prostate conditions, genital tract inflammation, and reproductive function in middle-aged men. METHODS: Three-hundred and eighty-two voluntary male subjects who underwent the screening for prostate health were recruited for the study. Semen quality and associated reproductive indicators, seminal inflammation, and prostate-related pathologies were evaluated. RESULTS: Sperm motility and prostate-related parameters were significantly impaired in patients with chronic prostatitis syndromes and lower urinary tract symptoms in comparison with controls. Elevated seminal markers of inflammation were in positive association with body mass index, prostate-specific antigen, and estradiol level in serum while in negative association with semen volume, total sperm count, and sperm motility. According to WHO reference limits, speculative cutoff values for WBC and IL-6 in semen to detect reduced sperm parameters were 0.342 M/mL and 56.8 ng/L, respectively. CONCLUSIONS: According to our data, one of the possible pathways for impaired reproductive quality in male subjects >45 years could be related to infection and inflammation in the genital tract with subsequent (partial) obstruction and damage of prostate and other male accessory glands.

Prostatic disorders in acromegalic patients experience of a Brazilian center.

INTRODUCTION: Published data suggest that patients with acromegaly have an increased prevalence of prostate disorders. OBJECTIVE: To evaluate prostatic disorders in acromegalic patients comparing these results after one year of treatment of acromegaly and with a group of healthy men. MATERIALS AND METHODS: This study was composed of two parts: sectional study comparing patients with healthy controls (baseline) and prospective, longitudinal study (at baseline and after one year of treatment). Forty acromegalic patients were enrolled and evaluated at baseline and after one year with the application of international prostatic symptoms score (IPSS), digital rectal examination, measurements of growth hormone (GH), insulin-like growth factor-I (IGF-I), insulin-like growth factor-binding protein-3 (IGFBP-3), sex hormone-binding globulin (SHBG), prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone, total and free prostate-specific antigen (PSA) levels and prostate ultrasonography (US). Thirty healthy men were selected as control group. RESULTS: We stratified patients and controls according to age, considering 40 years-old as cut off. Healthy controls under 40 had IPSS values lower than acromegalic patients. When considering only older patients and controls prostate hyperplasia and structural abnormalities were more frequent in acromegalics. After one year of treatment there was significant decrease in GH, IGF-I and prostate volume in acromegalics over 40 years-old. CONCLUSIONS: Acromegalics under 40 have more urinary symptoms according to IPSS and above 40 years-old higher frequency of structural changes and increased prostate volume than healthy men. Significant reduction of GH and IGF-I levels during treatment of acromegaly leads to decrease in the prostate volume.

[Composition and morphology of stones in enlarged prostatic utricle].

OBJECTIVE: To investigate the composition and morphology of the stones in the enlarged prostatic utricle (EPU). METHODS: We took out 36 EPU stones from 11 patients by transurethral fenestration between 1992 and 2011, and analyzed the stones by scanning electron microscopy, x-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIS). RESULTS: Under the scanning electron microscope, all the EPU stones were constituted of many intensive minicrystals and amorphous matrix. XRD and FTIS revealed that all were hydroxyapatite crystal. CONCLUSION: EPU stones belong to the category of prostatic pseudo-calculi, whose formation is ascribed not to the abnormal change of urine composition, but to the continuous secretion, absorption and concentration of EPU liquid and ablated epithelial cells from the EPU.

[Urology. Trends in prostatic diseases in 2012]. / Urologie. "Revisitons la prostate!".

This article discusses the management of prostate disease and new therapeutic approaches as a result from epidemiological and physiopathological links between benign prostatic hyperplasia and erectile dysfunction.

Proliferative, structural and molecular features of the Mdx mouse prostate.

The prostate is fundamental to the male reproductive process, and the stroma-epithelium interaction has an important role in prostate maintenance. Studies suggest that dystroglycan (DG) plays a role in cancer development in various organs. Thus, the aims of this work were to characterize morphological and proliferative features of the prostatic stroma and epithelium of mdx mice; to verify the immunolocalization of the α and ß DG, IGF-1 and laminin α3 receptors; and to relate those structural and molecular events to prostate pathogenesis and to verify the viability of this experimental model in prostate studies. Thirty male mice (mdx and C57BL10/Uni) were divided into control and mdx groups. Samples from the ventral prostate were collected for immunological, Western Blotting, transmission electron microscopy and morphometric analyses. Oestradiol and testosterone measurements were verified. The results showed diminished testosterone and increased oestradiol levels in the mdx group. Atrophied cells and hypertrophied stroma were seen in the mdx mice. Weak α and ß DG and laminin α3 immunolocalization was demonstrated in the mdx group. Intense insulin-like growth factor receptor α-1 (IGFRα-1) localization was identified in the mdx animals. Thus, mdx animals showed changes in molecular and structural integrity and proliferation signals, leading to glandular homoeostasis imbalance, and compromise of prostate function. Also, the steroid hormone imbalance and the increased IGF-1 receptor level detected in mdx mice could be considered as a crucial factor in the pathogenesis of prostatic disorders.

Does Prostate Artery Embolization (PAE) Improve Voiding Symptoms, Storage Symptoms, or Both?

INTRODUCTION: Many studies have looked at global changes in the International Prostate Symptom Score (IPSS) following PAE; however, no studies have examined the breakdown between storage and voiding symptoms. We aimed to explore the extent to which PAE improves storage symptoms in relation to voiding symptoms. METHOD: This single-center, prospective cohort study recruited consecutive patients undergoing PAE from June 2012 to June 2016. The IPSS breakdown was recorded pre-PAE, at 3 months and 12 months post-PAE. Planned statistical analysis included the paired t test. RESULTS: A total of 43 patients were recruited (mean age 64.72 ± 6.27, prostate volume 88.65 ± 37.23 cm3, IPSS 23.02 ± 5.84, QoL 4.98 ± 1.01, PSA 4.2 ± 2.8). Storage symptoms were more frequently the most severe symptom (58.1%). Voiding score (13.35-5.39, p < 0.001) and storage score (9.67-5.08, p < 0.001) both improved; however, voiding improved to a greater extent (1.9 vs. 1.5 mean per question, p = 0.023). PAE was most consistent when improving storage symptoms ('Urgency' improved in 86% patients, 'Frequency' and 'Nocturia' 77%). CONCLUSION: Storage symptoms are a significant problem for patients with benign prostatic obstruction. PAE is an effective treatment for both storage and voiding symptoms. More research is needed to evaluate how this compares with surgical techniques.

Eight Days of Water-Only Fasting Promotes Favorable Changes in the Functioning of the Urogenital System of Middle-Aged Healthy Men.

The aim of this study was to determine whether, after 8 days of water-only fasting, there are changes in the efficiency of the lower urinary tract, the concentration of sex hormones, and the symptoms of prostate diseases in a group of middle-aged men (n = 14). For this purpose, before and after 8 days of water-only fasting (subjects drank ad libitum moderately mineralized water), and the following somatic and blood concentration measurements were made: total prostate specific antigen (PSA-T), free prostate specific antigen (PSA-F), follicle stimulating hormone (FSH), luteotropic hormone (LH), prolactin (Pr), total testosterone (T-T), free testosterone (T-F), dehydroepiandrosterone (DHEA), sex hormone globulin binding (SHGB), total cholesterol (Ch-T), ß-hydroxybutyrate (ß-HB). In addition, prostate volume (PV), volume of each testis (TV), total volume of both testes (TTV), maximal urinary flow rate (Qmax), and International Prostate Symptom Score (IPSS) values were determined. The results showed that after 8 days of water-only fasting, Qmax and IPSS improved but PV and TTV decreased significantly. There was also a decrease in blood levels of PSA-T, FSH, P, T-T, T-F, and DHEA, but SHGB concentration increased significantly. These results indicate that 8 days of water-only fasting improved lower urinary tract functions without negative health effects.

Impact of diabetes and obesity on the prostate and urethra: implications to improved bladder dysfunction understanding and treatment.

PURPOSE: Alterations in bladder function are well documented in response to diabetes and obesity. Nonetheless, clinical manifestations of bladder dysfunction are diverse and the efficacy of available therapy is suboptimal. Since the bladder is only 1 component of the lower urinary tract, we explored existing evidence for the potential contribution(s) of other major lower urinary tract structures to diabetes and obesity related bladder dysfunction, namely the prostate and the urethra. MATERIALS AND METHODS: We performed a MEDLINE database search of the relevant literature. RESULTS: A relatively large literature exists on bladder dysfunction and the urethra. However, when additional search terms were added, such as prostate, diabetes and obesity, there was a dramatic decrease in the number of retrieved citations. These observations are consistent with the vanishingly small available literature on the impact of diabetes on prostatic biology and urethral function, and their potential impact on bladder physiology/dysfunction. The available literature documents significant alterations in prostatic biology and urethral function in the setting of diabetes and/or obesity. CONCLUSIONS: The observed diversity in diabetes and obesity related bladder dysfunction, and the variable efficacy of currently available treatments may be related at least in part to the differential impact of these disease states on the complex integration of bladder function with other structural components of the lower urinary tract, namely the urethra and the prostate. More comprehensive investigations of this system should lead to improved understanding of the mechanistic basis for the observed pathophysiology and identify novel treatment regimens.

Evaluation of seminal citrate level by 1H nuclear magnetic resonance spectroscopy in men with spinal cord injury.

STUDY DESIGN: A case-control evaluating seminal citrate in patients with spinal cord injury (SCI). OBJECTIVE: Several studies have shown neurological prostatic dysfunction in patients with SCI, as confirmed by low levels of seminal prostate-specific antigen (PSA), which is used as a parameter of gland activity. However, seminal citrate, produced almost exclusively by the prostate, could also be used as a marker of prostate function. Thus, the objective of this study was to determine whether SCI causes any changes in seminal citrate concentration and to compare the results obtained for patients and healthy men (controls). SETTING: The study was carried out in Brazil. METHODS: We studied 30 men with SCI aged on average 37.77+/-10.04 years and 30 controls aged on average 38.03+/-10.06 years. Blood and semen samples were collected after 3 days of abstinence from ejaculation. Fifteen minutes after collection, semen was stored in liquid nitrogen and the samples were submitted to (1)H nuclear magnetic resonance ((1)H NMR). Serum was stored at a controlled temperature of -70 to -79 degrees C and later used for the determination of testosterone, prolactin and total PSA using an AxSYM instrument and Abbott reagents. RESULTS: The median concentration of seminal citrate was significantly lower in patients than in controls (521.65 versus 858.30 mg per 100 ml, P<0.001). CONCLUSIONS: Patients with SCI have a significant reduction of seminal citrate as a consequence of neurological dysfunction of the prostate.

Concurrent improvement of the metabolic syndrome and lower urinary tract symptoms upon normalisation of plasma testosterone levels in hypogonadal elderly men.

Central obesity in adulthood, the metabolic syndrome, erectile failure and lower urinary tract symptoms (LUTS) are all associated with lower-than-normal testosterone levels, although the relationship between testosterone and LUTS appears weak. The metabolic syndrome is associated with an overactivity of the autonomic nervous system. Alternatively, the metabolic syndrome is associated with markers of inflammation, such as C-reactive protein (CRP), maybe signalling intraprostatic inflammation. A large cohort of 95 middle-aged to elderly hypogonadal men (T levels 5.9-12.1 nmol l(-1)) were treated with parenteral testosterone undecanoate and its effects on the metabolic syndrome {waist circumference, cholesterol, CRP and LUTS [residual bladder volume (RBV), International Prostate Symptoms Score (IPSS), prostate volume, prostate-specific antigen (PSA)]} were evaluated. Along with the improvements of the metabolic syndrome, there was a significant decline of the values of the IPSS, RBV and CRP. There was a (low) level of correlation between the decline of waist circumference and residual volume of urine but not with IPSS and prostate size. Along with the improvement of the metabolic syndrome upon testosterone administration, there was also an improvement of the IPSS and of RBV of urine and CRP. The mechanism remains to be elucidated.

[A man with a palpable node on the prostate]. / Een palpabele nodus in de prostaat.

A 64-year-old man was referred to our urology outpatient clinic with lower urinary tract symptoms (LUTS). During rectal examination a smooth nodule was identified. MRI-images showed a prostatic cyst, originating from the utriculus. An utriculus cyst is a relatively rare finding and originates from a persistent remnant of the Müllerian duct.

Development of a CFD urethral model to study flow-generated vortices under different conditions of prostatic obstruction.

A novel, non-invasive method to diagnose bladder outlet obstruction involves the recording of noise with a contact microphone pressed against the perineum (between anus and scrotum). This noise results from flow-generated vortices caused by prostatic obstruction. We developed a computational fluid dynamic (CFD) urethral model including urethral geometry to study the relation between generated noise and the degree of obstruction. This model comprised a bladder, bladder neck, prostate and urethra. Calculations were carried out at four bladder pressures, five degrees of obstruction and three obstruction shapes. For each of the sixty simulations, the velocity and pressure distributions along the urethra were calculated including wall shear stresses to localize flow transition from disturbed to normal. Negative pressures at the obstruction outlet induced recirculation of flow. The location of transition was independent of the applied bladder pressure, but it depended primarily on the degree and secondarily on the shape of the obstruction. Based on the presented results, we hypothesize that the location of the maximum amplitude of perineal noise mainly depends on the degree and shape of the prostatic obstruction. Our future aim is to test our hypothesis in male patients and to extend the presented model to 3D with a viscoelastic urethral wall to calculate the fluid-wall interaction.