Alterations in detrusor contractility in rat model of bladder cancer.

Urinary incontinence of idiopathic nature is a common complication of bladder cancer, yet, the mechanisms underlying changes in bladder contractility associated with cancer are not known. Here by using tensiometry on detrusor smooth muscle (DSM) strips from normal rats and rats with bladder cancer induced by known urothelial carcinogen, N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), we show that bladder cancer is associated with considerable changes in DSM contractility. These changes include: (1) decrease in the amplitude and frequency of spontaneous contractions, consistent with the decline of luminal pressures during filling, and detrusor underactivity; (2) diminution of parasympathetic DSM stimulation mainly at the expense of m-cholinergic excitatory transmission, suggestive of difficulty in bladder emptying and weakening of urine stream; (3) strengthening of TRPV1-dependent afferent limb of micturition reflex and TRPV1-mediated local contractility, promoting urge incontinence; (4) attenuation of stretch-dependent, TRPV4-mediated spontaneous contractility leading to overflow incontinence. These changes are consistent with the symptomatic of bladder dysfunction in bladder cancer patients. Considering that BBN-induced urothelial lesions in rodents largely resemble human urothelial lesions at least in their morphology, our studies establish for the first time underlying reasons for bladder dysfunction in bladder cancer.

Reducing Neuron Apoptosis in the Pontine Micturition Center by Nerve Root Transfer for Restoration of Micturition Function after Spinal Cord Injury.

OBJECTIVE: The rate of neuronal apoptosis increases after spinal cord injury (SCI). Anastomosing the normal nerve roots above the SCI level to the injured sacral nerve roots can enhance the functional recovery of neurons. Therefore, we evaluated the effect of sacral nerve root transfer after SCI on pontine neuronal survival. METHODS: Sprague-Dawley rats were randomly divided into three groups: Group A, reconstruction of afferent and efferent nerve pathways of the bladder after SCI; Group B, SCI only; and Group C, control group. We examined pontine neuronal morphology using hematoxylin and eosin (H&E) staining after SCI and nerve transfer. Bcl-2 and Bax protein expression changes in the pontine micturition center were quantified by immunohistochemistry. The number of apoptotic neurons was determined by TUNEL staining. We examined pontine neuronal apoptosis by transmission electron microscopy (TEM) at different time points. RESULTS: H&E staining demonstrated that the number of neurons had increased in Group A, but more cells in Group B displayed nuclear pyknosis, with the disappearance of the nucleus. Compared with Group B, Group A had significantly higher Bcl-2 expression, significantly lower Bax expression, and a significantly higher Bcl-2/Bax ratio. The number of apoptotic neurons and neuron bodies in Group A was significantly lower than that in Group B, as indicated by TUNEL staining and TEM. CONCLUSIONS: These findings demonstrate that lumbosacral nerve transfer can reduce neuronal apoptosis in the pontine micturition center and enhance functional recovery of neurons. This result further suggests that lumbosacral nerve transfer can be used as a new approach for reconstructing bladder function after spinal cord injury.

Investigating the associations of mucosal P2Y6 receptor expression and urinary ATP and ADP concentrations, with symptoms of overactive bladder.

AIM: To characterize purinergic signaling in overactive bladder (OAB). METHODS: Mucosal biopsies were taken by flexible cystoscopy from patients with storage symptoms referred to Urology Departments of collaborating hospitals. Immunohistochemistry (n = 12) and Western blot analysis (n = 28) were used to establish the qualitative and quantitative expression profile of P2Y6 in human mucosa. Participants from the general population provided a mid-stream urine sample. Bioluminescent assays were used to quantify adenosine triphosphate (ATP; n = 66) and adenosine diphosphate (ADP; n = 60) concentrations, which were normalized to creatinine (Cr) concentration. All participants completed a questionnaire (International Consultation on Incontinence Questionnaire - Overactive Bladder) to score urinary symptoms of OAB. RESULTS: P2Y6 immunoreactivity, more prominent in the urothelium (colocalized with the uroepithelial marker pan-cytokeratin), was more greatly expressed in OAB compared to age- and sex-matched controls (benign prostatic hyperplasia) without OAB symptoms. Mucosal P2Y6 was positively correlated only with incontinence (P = .009). Both urinary ATP and its hydrolysis product, ADP, an agonist to P2Y6, were positively correlated with total OAB symptom score (P = .010 and P = .042, respectively). CONCLUSIONS: The positive correlation of P2Y6 only with incontinence may indicate a different phenotype in OAB wet and warrants further investigation. Positive correlations of ATP and ADP with total OAB symptom score demonstrate upregulation in purinergic signaling in OAB; shown previously only in animal models. Further research is required to validate whether purinoceptors are indeed new therapeutic targets for this highly prevalent symptom complex.

Genome-Wide Association Study for Urinary and Fecal Incontinence in Women.

PURPOSE: Urinary incontinence and fecal incontinence are common disorders in women that negatively impact quality of life. In addition to known health and lifestyle risk factors, genetics may have a role in continence. Identification of genetic variants associated with urinary incontinence and fecal incontinence could result in a better understanding of etiologic pathways, and new interventions and treatments. MATERIALS AND METHODS: We previously generated genome-wide single nucleotide polymorphism data from Nurses' Health Studies participants. The participants provided longitudinal urinary incontinence and fecal incontinence information via questionnaires. Cases of urinary incontinence (6,120) had at least weekly urinary incontinence reported on a majority of questionnaires (3 or 4 across 12 to 16 years) while controls (4,811) consistently had little to no urinary incontinence reported. We classified cases of urinary incontinence in women into stress (1,809), urgency (1,942) and mixed (2,036) subtypes. Cases of fecal incontinence (4,247) had at least monthly fecal incontinence reported on a majority of questionnaires while controls (11,634) consistently had no fecal incontinence reported. We performed a genome-wide association study for each incontinence outcome. RESULTS: We identified 8 single nucleotide polymorphisms significantly associated (p <5×10-8) with urinary incontinence located in 2 loci, chromosomes 8q23.3 and 1p32.2. There were no genome-wide significant findings for the urinary incontinence subtype analyses. However, the significant associations for overall urinary incontinence were stronger for the urgency and mixed subtypes than for stress. While no single nucleotide polymorphism reached genome-wide significance for fecal incontinence, 4 single nucleotide polymorphisms had p <10-6. CONCLUSIONS: Few studies have collected genetic data and detailed urinary incontinence and fecal incontinence information. This genome-wide association study provides initial evidence of genetic associations for urinary incontinence and merits further research to replicate our findings and identify additional risk variants.

Prelamin A overexpression promotes detrusor calcification/aging in urinary incontinence via prelamin A accumulation.

Urinary incontinence (UI) is known as a distressing condition particularly among older adults, and negatively associated with health-related quality of life in both males and females. Prelamin A accumulation has been found in all progeroid laminopathies and is obviously linked to cell and organism aging. Therefore, this study was expected to investigate the effect of prelamin A on detrusor on UI. Prelamin A expression in clinical and animal samples was detected. To investigate the degree of prelamin A accumulation and detrusor calcification/aging, the detrusor cells were subcultured separately into low and high passage. The low-passage subculture cells were treated with transfection of overexpressed prelamin A plasmid, and transfection of overexpressed prelamin A plasmid and application of farnesyl transferase inhibitor (FTIs) H-9279, respectively. Zmpste24, Icmt and lamin A/C expression were detected to explore how prelamin A affected detrusor calcification/aging. Prelamin A was overexpressed in aged detrusor cells, indicating prelamin A expression was positively related to the age of subjects. The degree of prelamin A accumulation and detrusor calcification/aging was higher in aged rats and high passage subculture cells. Zmpste24, Icmt and lamin A/C were poorly expressed in cells transfected with overexpressed prelamin A, as well as cell proliferation activity decreased and calcium deposition and apoptotic rate increased. Furthermore, we also found that the effect of overexpressed prelamin A was lost when cells were treated with H-9279. These findings provide evidence that prelamin A overexpression impairs degradation of its farnesylated form, thus causing prelamin A accumulation which induces detrusor calcification/aging in UI.

Age and multiparity related urethral sphincter muscle dysfunction in a rabbit model: Potential roles of TGF-ß and Wnt-ß catenin signaling pathways.

AIMS: Prior studies demonstrate increased incidence of urinary incontinence (UI) in the geriatric population which affects their quality of life. Pathophysiology of UI in the geriatric population and the underlying molecular mechanisms are still unclear. To elucidate these mechanisms, we performed a pre-clinical study in a rabbit model and the objectives were to (i) determine the effect of aging as well as multiparity on urethral sphincter muscle thickness and urethral closing pressure (UCP); (ii) examine the role of fibrosis and atrophy; and (iii) elucidate the molecular pathways that mediate fibrosis and atrophy in the urethral tissue. METHODS: New Zealand White female rabbits (n = 6 each; young 6-12 months and old over 30 months of age) were anesthetized and urethral muscle thickness and sphincter closure function were measured. Rabbits were then sacrificed and urethral tissues (bladder neck and mid-urethra) were collected to process for immunostaining as well as for molecular studies for markers for fibrosis (ß-catenin which is an important mediator of Wnt signaling, Collagen-1, and TGF-ß) and atrophy (MuRF-1). RESULTS: Our studies showed a significant decrease in the urethral sphincter muscle thickness and closure function with age. Age-related increase in protein and mRNA expression levels of fibrosis, as well as atrophy markers were observed in the bladder neck and mid-urethral tissues. CONCLUSIONS: Age and multiparity related increase in fibrosis and atrophy of urethral sphincter muscles may contribute to impaired urethral closure function seen in old animals.

Endoplasmic reticulum stress contributes to the pathogenesis of stress urinary incontinence in postmenopausal women.

OBJECTIVE: To investigate the relationship between endoplasmic reticulum stress (ERS) and the pathogenesis of stress urinary incontinence (SUI) in postmenopausal women. METHODS: Anterior vaginal wall tissue was collected from postmenopausal women with SUI and control subjects. Western blotting was performed for glucose-regulated protein (GRP78), inositol-requiring enzyme 1(IRE1), protein kinase-like endoplasmic reticulum kinase (PERK), activating transcription factor 6 (ATF6), C/EBP-homologous protein (CHOP), and B-cell lymphoma 2 (Bcl-2). Additionally, mRNA expression levels of PERK, activating transcription factor 4 (ATF4), and CHOP were examined by real-time polymerase chain reaction. RESULTS: GRP78 protein and mRNA expression levels were significantly lower in women with SUI, compared with control subjects. PERK and p-PERK expression levels were higher in women with SUI than in control subjects. However, no differences in IRE1 or ATF6 expression levels were observed in either group. Notably, higher CHOP and lower Bcl-2 protein expression levels were detected in women with SUI, compared with control subjects. Furthermore, PERK, ATF4, and CHOP mRNA expression levels were significantly higher in women with SUI than in control subjects. CONCLUSIONS: Alterations of ERS markers in SUI suggest that ERS may be involved in the development of SUI in postmenopausal women.

[Absorbent products for urinary incontinence management]. / Place des protections dans la prise en charge de l'incontinence urinaire.

INTRODUCTION: Despite therapeutic strategies of female and male urinary incontinence (UI) are currently well defined, there is no precise indication of the real place or strategy use of absorbent products regardless of the etiology of the incontinence or the clinical context. METHODS: We performed a research from the PubMed database using the following keywords: (urinary incontinence [MESH Terms]) AND absorbent pad [MeSH Terms]; allowing us to isolate 362 articles. RESULTS: Many protections designs are available over-the-counter without prescription and without reimbursement in France. For "light UI", disposable insert pads are the design that seems to be the most suitable for women, compared to disposable menstrual pads, OR=0.27 [0.14, 0.52], washable pants with integral pad OR=0.12 [0.06, 0.26] or washable insert pads OR=0.05 [0.02, 0.26]. For moderate to severe UI, there is no "best universal product". There are differences between the gender and the use of a panel of protections seems the most appropriate. Both women and men prefer pull-ups to disposable insert pads, OR=0.41 [0.20, 0.87] and OR=0.39 [0.22, 0.68] respectively. In men, a preference in 70 % of subjects for urisheats is observed compared to the protections they usually use (P=0.02). The use of protections improves independence in daily OR activities=0.102 [0.046, 0.158] and quality of life related to UI OR=4.40 [1.74, 7.07] compared to patients not using protections. Despite this, their use must remain cautious because of the potential infectious urinary complications, more frequent in particular in institutional people, with 41 % of users developing at least one urinary infection over an evaluation period of 12 months vs. 11 % of non-users (P=0.001), or immuno-allergic with the "dermatitis associated incontinence" whose prevalence can reach a rate of 50 %. CONCLUSION: Comparative analyzes of risk-benefit, economic costs, patient satisfaction, protections vs. other measures are lacking. It is necessary to continue the development of these products and to compare more precisely their intrinsic characteristics, to best support patients choices.

The role of ATP signalling in response to mechanical stimulation studied in T24 cells using new microphysiological tools.

The capacity to store urine and initiate voiding is a valued characteristic of the human urinary bladder. To maintain this feature, it is necessary that the bladder can sense when it is full and when it is time to void. The bladder has a specialized epithelium called urothelium that is believed to be important for its sensory function. It has been suggested that autocrine ATP signalling contributes to this sensory function of the urothelium. There is well-established evidence that ATP is released via vesicular exocytosis as well as by pannexin hemichannels upon mechanical stimulation. However, there are still many details that need elucidation and therefore there is a need for the development of new tools to further explore this fascinating field. In this work, we use new microphysiological systems to study mechanostimulation at a cellular level: a mechanostimulation microchip and a silicone-based cell stretcher. Using these tools, we show that ATP is released upon cell stretching and that extracellular ATP contributes to a major part of Ca2+ signalling induced by stretching in T24 cells. These results contribute to the increasing body of evidence for ATP signalling as an important component for the sensory function of urothelial cells. This encourages the development of drugs targeting P2 receptors to relieve suffering from overactive bladder disorder and incontinence.

Path of translational discovery of urological complications of obesity and diabetes.

Diabetes mellitus (DM) is a prevalent chronic disease. Type 1 DM (T1DM) is a metabolic disorder that is characterized by hyperglycemia in the context of absolute lack of insulin, whereas type 2 DM (T2DM) is due to insulin resistance-related relative insulin deficiency. In comparison with T1DM, T2DM is more complex. The natural history of T2DM in most patients typically involves a course of obesity to impaired glucose tolerance, to insulin resistance, to hyperinsulinemia, to hyperglycemia, and finally to insulin deficiency. Obesity is a risk factor of T2DM. Diabetes causes some serious microvascular and macrovascular complications, such as retinopathy, nephropathy, neuropathy, angiopathy and stroke. Urological complications of obesity and diabetes (UCOD) affect quality of life, but are not well investigated. The urological complications in T1DM and T2DM are different. In addition, obesity itself affects the lower urinary tract. The aim of this perspective is to review the available data, combined with the experience of our research teams, who have spent a good part of last decade on studies of association between DM and lower urinary tract symptoms (LUTS) with the aim of bringing more focus to the future scientific exploration of UCOD. We focus on the most commonly seen urological complications, urinary incontinence, bladder dysfunction, and LUTS, in obesity and diabetes. Knowledge of these associations will lead to a better understanding of the pathophysiology underlying UCOD and hopefully assist urologists in the clinical management of obese or diabetic patients with LUTS.

Sulforaphane Ameliorates Bladder Dysfunction through Activation of the Nrf2-ARE Pathway in a Rat Model of Partial Bladder Outlet Obstruction.

Purpose. We evaluated the effect of sulforaphane (SFN) treatment on the function and changes of expression of Nrf2-ARE pathway in the bladder of rats with bladder outlet obstruction (BOO). Materials and Methods. A total of 18 male Sprague-Dawley rats at age of 8 weeks were divided into 3 groups (6 of each): the sham operated group, the BOO group, and the BOO+SFN group. We examined histological alterations and the changes of oxidative stress markers and the protein expression of the Nrf2-ARE pathway. Results. We found that SFN treatment could prolong micturition interval and increase bladder capacity and bladder compliance. However, the peak voiding pressure was lower than BOO group. SFN treatment can ameliorate the increase of collagen fibers induced by obstruction. SFN treatment also increased the activity of SOD, GSH-Px, and CAT compared to the other groups. The level of bladder cell apoptosis was decreased in BOO rats with SFN treatment. Moreover, SFN could reduce the ratio of Bax/Bcl-2 expression. Furthermore, SFN could activate the Nrf2 expression with elevation of its target antioxidant proteins. Conclusions. The sulforaphane-mediated decrease of oxidative stress and activation of the Nrf2-ARE pathway may ameliorate bladder dysfunction caused by bladder outlet obstruction.

Genitourinary syndrome of menopause: an overview of clinical manifestations, pathophysiology, etiology, evaluation, and management.

Genitourinary syndrome of menopause, a new term for a condition more renowned as atrophic vaginitis, is a hypoestrogenic condition with external genital, urological, and sexual implications that affects >50% of postmenopausal women. Due to sexual embarrassment and the sensitive nature of discussing symptoms, genitourinary syndrome of menopause is greatly underdiagnosed. The most up-to-date literature pertaining to clinical manifestations, pathophysiology, etiology, evaluation, and management of genitourinary syndrome of menopause is comprehensively reviewed. Early detection and individually tailored pharmacologic (eg, estrogen therapy, selective estrogen receptor modulator, synthetic steroid, oxytocin, and dehydroepiandrosterone) and/or nonpharmacologic (eg, laser therapies, moisturizers and lubricants, homeopathic remedies, and lifestyle modifications) treatment is paramount for not only improving quality of life but also for preventing exacerbation of symptoms in women with this condition.

Transplantation of bone marrow-derived mesenchymal stem cells expressing elastin alleviates pelvic floor dysfunction.

BACKGROUND: Pelvic floor dysfunction (PFD) is a group of clinical conditions including stress urinary incontinence (SUI) and pelvic organ prolapse (POP). The abnormality of collagen and elastin metabolism in pelvic connective tissues is implicated in SUI and POP. METHODS: To reconstitute the connective tissues with normal distribution of collagen and elastin, we transduced elastin to bone marrow-derived mesenchymal stem cells (BMSC). Elastin-expressing BMSCs were then differentiated to fibroblasts using bFGF, which produced collagen and elastin. To achieve the sustained release of bFGF, we formulated bFGF in poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NP). RESULTS: In an in vitro cell culture system of 7 days, when no additional bFGF was administrated, the initial PLGA-loaded bFGF NP induced prolonged production of collagen and elastin from elastin-expressing BMSCs. In vivo, co-injection of PLGA-loaded bFGF NP and elastin-expressing BMSCs into the PFD rats significantly improved the outcome of urodynamic tests. Together, these results provided an efficient model of connective tissue engineering using BMSC and injectable PLGA-loaded growth factors. CONCLUSIONS: Our results provided the first instance of a multidisciplinary approach, combining both stem cell and nanoparticle technologies, for the treatment of PFD.

Instrumentación transuretral en portadores de esfínter urinario artificial. Presentación y discusión de tres casos clínicos / Transurethral instrumentation in patients with artificial urinary sphincter. Presentation and discussion of three clinical cases

El tratamiento para la incontinencia urinaria masculina de esfuerzo severa es la colocación de un esfínter urinario artificial (EUA). La etiología de la incontinencia con frecuencia es la cirugía prostática previa. Los resultados funcionales son buenos con una tasa aceptable de complicaciones. Las complicaciones son más frecuentes si existe radioterapia previa o se realizan procedimientos transuretrales sin tener en cuenta la presencia del manguito del EUA. Cuando es necesaria la cirugía transuretral, por ejemplo por tumor vesical, es necesario realizar el desabrochado del manguito esfinteriano. Los sondajes uretrales precisan también desactivar el manguito y manipular la uretra con sumo cuidado, evitando su manipulación siempre que sea posible. Se presentan tres casos muy complejos de pacientes portadores de EUA que han precisado diversas soluciones ante manipulación uretral y presencia de complicaciones como estenosis de uretra (AU)

Artificial urinary sphincter (AS) is the gold standard treatment for severe male urinary stress incontinence. The etiology of incontinence is often previous prostate surgery as a radical prostatectomy. Functional results are good with an acceptable rate of complications. If there is prior radiotherapy complications are more frequent. When transurethral surgery, for example for bladder tumor is needed, it is necessary unbuttoned the sleeve. Urethral soundings need also turn off the sleeve and manipulate the urethra carefully, avoiding handling whenever possible. We present three very complex cases of patients with US showing several solutions to urethral manipulation and to resolve complications such as urethral perforation and stricture (AU)

Evaluación y prevalencia de incontinencia urinaria tras prostatectomía radical: análisis de una serie histórica / Assessment and prevalence of urinary incontinence after radical prostatectomy: analysis of a historical series

OBJETIVO: El tratamiento del cáncer de próstata mediante prostatectomía radical puede ocasionar incontinencia urinaria. Nuestro objetivo es calcular la prevalencia de incontinencia urinaria a través del análisis de una serie histórica, analizar las características de las pérdidas y los factores influyentes en la aparición de incontinencia. MÉTODOS: Estudio descriptivo, observacional y retrospectivo de las variables clinicopatológicas de 1310 pacientes intervenidos entre 1989-2011. La prevalencia se calcula a los 12 meses de la cirugía usando la definición de ICS. Estudio transversal para completar el cuestionario ICIQ-SF y las protecciones usadas. Se estudia la serie completa y en dos grupos según características oncológicas. Se realiza estudio descriptivo, comparativo y predictivo. RESULTADOS: La prevalencia de la serie es de 23.5% con 296 pacientes. 279 incontinentes completaron el cuestionario ICIQ-SF con una media de 11.1±4.03. 16.4% de los pacientes intervenidos usan al menos 1 protección al día, de ellos el 69% usan compresas (11.4% del total), y el 22% pañales clásicos. El 8% usa más de una protección al día. Las características clinicopatológicas dividen la serie en dos grupos distintos: 1989-1999 con una prevalencia de 24.6% y grupo 2000-2011 con 22.8%. El análisis multivariado encontramos la edad (65 años) (OR:1.65, p = 0.013) y volumen prostático (50cc) (OR:1.49, p = 0.029) influyentes de forma independiente. CONCLUSIONES: La incontinencia urinaria es una enfermedad de cierta prevalencia, que varía según la definición que utilicemos. La situación más frecuente en los pacientes incontinentes es tener pérdidas varias veces al día (42.2%), poca cantidad (59.1%), usando protecciones tipo compresa (69%) y afectando la calidad de vida de forma leve-moderada (0-7: 88.2%). Las variables predictivas fueron la edad (65 años) y el volumen prostático (50cc). La evolución histórica de los pacientes no influye en la prevalencia de incontinencia urinaria

OBJECTIVES: Prostate cancer can be treated by radical prostatectomy and provoke urinary incontinence as secondary effect. Our aim is to calculate the prevalence of urinary incontinence, characteristics of leakage and influential factors, through a historical series. METHODS: We perform a descriptive, observational and retrospective study of 1310 patients who received treatment for PCa between 1989 and 2011. Prevalence was obtained after 12 months of recovery and using ICS definition. To complete ICIQ-SF and number of pads/day used we perform a cross-sectional study. The series is studied globally and divided in two groups according to oncologic characteristics. We perform a descriptive, comparative and predictive analysis. RESULTS: Prevalence of the series was 23.5%, 296 patients. 279 incontinent patients completed ICIQ-SF with a mean score of 11.1±4.03. 16.4% of the patients use 1 pad/day or none, 69% (11.4% of the total) use compress and 22% diapers. 8% of the total use more than 1 pad/day. Clinico-pathological factors divide series in two groups: 1989-1999 with a prevalence of 24.6% and 2000-2011 with 22.8%. Multivariate analysis shows influential factors: age (65 years) (OR:1.65, p = 0.013) and prostate volume (50cc) (OR:1.49, p = 0.029). Concluisions: Urinary incontinence is a disease with some prevalence that varies depending on definition. The most common situation was to leak several times a day (42.2%), a small amount (59.1%), using compress (69%) most of incontinents with a mild (0-7: 88.2%) impact on quality of life. Predictive factors were age (65 years) and prostate volume (50cc). The historical changes does not influence over prevalence

Histopathology of Incontinence-Associated Skin Lesions: Inner Tissue Damage Due to Invasion of Proteolytic Enzymes and Bacteria in Macerated Rat Skin.

A common complication in patients with incontinence is perineal skin lesions, which are recognized as a form of dermatitis. In these patients, perineal skin is exposed to digestive enzymes and intestinal bacterial flora, as well as excessive water. The relative contributions of digestive enzymes and intestinal bacterial flora to skin lesion formation have not been fully shown. This study was conducted to reveal the process of histopathological changes caused by proteases and bacterial inoculation in skin maceration. For skin maceration, agarose gel containing proteases was applied to the dorsal skin of male Sprague-Dawley rats for 4 h, followed by Pseudomonas aeruginosa inoculation for 30 min. Macroscopic changes, histological changes, bacterial distribution, inflammatory response, and keratinocyte proliferation and differentiation were examined. Proteases induced digestion in the prickle cell layer of the epidermis, and slight bleeding in the papillary dermis and around hair follicles in the macerated skin without macroscopic evidence of erosion. Bacterial inoculation of the skin macerated by proteolytic solution resulted in the formation of bacteria-rich clusters comprising numerous microorganisms and inflammatory cells within the papillary dermis, with remarkable tissue damage around the clusters. Tissue damage expanded by day 2. On day 3, the proliferative keratinocyte layer was elongated from the bulge region of the hair follicles. Application of proteases and P. aeruginosa induced skin lesion formation internally without macroscopic erosion of the overhydrated area, suggesting that the histopathology might be different from regular dermatitis. The healing process of this lesion is similar to transepidermal elimination.

Efectos adversos a largo plazo de la fase de llenado vesical en varones tratados con radioterapia pélvica / Long-term adverse effects on bladder filling phase in males submitted to the pelvic radiotherapy

INTRODUCCIÓN: Los efectos adversos de la radioterapia externa RT sobre la función del tracto urinario inferior de los varones están pobremente estudiados. OBJETIVO: Estudiar y cuantificar los efectos a largo plazo sobre la fase de llenado en varones tratados con radioterapia. MÉTODOS: Estudio comparativo retrospectivo de una cohorte de 99 varones tratados con radioterapia externa, realizada con una media de 4,7 años antes del inicio del estudio. Los pacientes estudiados fueron sometidos a radioterapia como tratamiento del cáncer de próstata localizado, tumor de colon y tumor de recto. Se utilizó como grupo control una cohorte de 97 hombres mayores de 50 años que no habían sido sometidos a tratamiento radioterápico. RESULTADOS: La capacidad vesical cistomanométrica y en el momento del primer deseo miccional fueron significativamente menores en el grupo tratado con radioterapia. El análisis univariante mostró una disminución de la acomodación vesical 3,5 veces mayor en el grupo tratado con radioterapia y un aumento del riesgo para desarrollar incontinencia de esfuerzo de 9,3 veces. No se encontraron diferencias en el riesgo de hiperactividad del detrusor. En el análisis multivariante la existencia de antecedentes de cirugía radical pelviana fue un factor de confusión para el desarrollo de incontinencia urinaria de esfuerzo, no siéndolo para la disminución de la acomodación vesical. CONCLUSIONES: El principal efecto adverso que se produce a largo plazo después del tratamiento con radioterapia pélvica es la disminución de la acomodación vesical durante la fase de llenado. El tratamiento con RT adyuvante produce alteraciones urinarias a largo plazo

OBJECTIVE: To describe and quantify the long-term adverse effects on filling phase of lower urinary tract function in males submitted to radiotherapy. METHODS: We performed a retrospective comparative study on a cohort of 99 men undergoing EBRT a mean of 4.7 years before for clinically localized prostate, rectum or colon neoplasia, and another cohort formed by 97 men over 50 years who did not undergo radiotherapy. RESULTS: Cystometric bladder capacity and bladder capacity at first voiding desire were significantly lower in the radiotherapy group. Univariate analysis showed that the radiotherapy group evinced a risk to present a diminished compliance of 3.5 times more and 9.3 times more to find stress urinary incontinence, but we did not found increased risk for detrusor overactivity. In multivariate analysis the history of radical surgery acted as a confounding factor in the risk of stress urinary incontinence, but not to suffer diminished bladder compliance. CONCLUSIONS: The main long-term adverse effect of pelvic radiotherapy on male bladder function during filling is the increased risk of low bladder compliance

Reflujo Vaginal y Urocolpos / Vesicovaginal Reflux and Urocolpos

OBJETIVOS: El reflujo vaginal (RV) o micción intravaginal es una causa de incontinencia urinaria diurna, con goteo postmiccional. El llenado retrógrado de la vagina durante la micción obedece a causas anatómicas predisponentes o funcionales. MÉTODOS: Exposición de casos clínicos. RESULTADO: Caso clínico 1.- Niña de 10 años, con infecciones de orina acompañadas de incontinencia postmicional a diario. En CUMS se aprecia, en las placas miccionales, la aparición progresiva de urocolpos, que desaparece parcialmente al finalizar la micción. Se inicia tratamiento con re-educación miccional con resolución de síntomas. Caso clínico 2.- Niña de 9 años, con antecedentes de Reflujo Vesicoureteral (RVU) corregido en la infancia que desde hace un año presenta incontinencia de escasa cuantía, postmiccional, con sensación de vaciado incompleto. Aporta ecografia pre y postmiccional normal, pero en la CUMS se aprecia RV, por lo que se inicia tratamiento específico con mejoría de los síntomas. Caso clínico 3.- Niña de 10 años con sobrepeso que consulta por incontinencia diurna, sin síntomas nocturnos. En CUMS se aprecia RV por lo que se establecen medidas conductuales. A los seis meses, las fugas han recurrido, al incumplir la paciente dichas medidas. Concluisones: Hasta un 12-15% de las niñas prepúberes que consultan por escapes de orina pueden presentar RV. El tratamiento consiste en la re-educación del hábito miccional, insistiendo en micciones frecuentes y programadas con un hábito postural correcto consistente en apertura de piernas e inclinación hacia delante, o bien, a horcajadas sobre el inodoro en posición contraria a la habitual

OBJECTIVE: Vesico-vaginal reflux (VVR) is defined as the reflux of urine into the vaginal vault during voiding, occasionally seen in pre- adolescent girls. The typical history consists in post voiding leaks in the daytime, that correspond to the progressive urine discharge from the vagina, after it has been filled up during micturition. We intend to show two cases presenting with significant urocolpos. METHODS: Description of two clinical cases observed in the pediatric urology office. RESULTS: Clinical case 1.- A 10-year-old girl presented with the complaint of diurnal incontinence (in the immediate post-voiding minutes). The early voiding phase in the cystourethrogram (VCUG) demonstrated progressive gross distension of the vagina (urocolpos) due to retrograde filling as the bladder emptied. The girl was managed with behavioural modifications, and was dry afterwards. Clinical case 2.- A 9-year-old girl presented with history of incomplete voiding. In infancy, she had right-sided vesicoureteral reflux (VUR) and was endoscopically treated at the age of 2. VCUG showed VVR, and no VUR. She was then successfully treated with behavioural modifications. Clinical case 3.- A 10-year-old girl complained of diurnal urinary incontinence, described as post voiding leaks. Again, a VCUG showed VVR and a small urocolpos. After re-education of voiding habits, leaks disappeared, but recurred 6 months afterwards, when she acknowledged no adherence to the therapy. DISCUSSION: Between 12 to 15% of girls referred to Urological clinics because of urine incontinence present VVR. In the absence of a clear anatomical obstruction, reflux happens as the urine flow encounters a natural obstacle in the labia majora usually in girls that close their legs as they void. Instructions on proper voiding form a key element in the management of VVR, and if not enough, the behavioural modification consists on a reverse position during voiding

A novel intracerebral hemorrhage-induced rat model of neurogenic voiding dysfunction: Analysis of lower urinary tract function.

Neurogenic lower urinary tract dysfunction (NLUTD) is a major problem in patients with various neurological disorders, and may result in debilitating symptoms and serious complications, including chronic renal failure and recurrent urinary tract infections. Clinically, stroke is associated with voiding dysfunction. However, lower urinary tract function evaluation in an intracerebral hemorrhage (ICH) model has not, to the best of our knowledge, been reported. Therefore, in the present study, lower urinary tract function in ICH-induced rats was investigated and the results were compared with those obtained in normal rats. The effects of ICH on peripheral bladder function and central micturition centers [medial preoptic area, ventrolateral gray, pontaine micturition center and spinal cord (lumbar 4 (L4)-L5)] were also examined. Adult female Sprague-Dawley rats were divided into two groups: Control ICH-induced. Induction of ICH in the hippocampal CA1 region was performed using a stereotaxic frame and type IV collagenase. The effects of ICH on the central micturition centers were investigated by simultaneously determining the extent of neuronal activation (c-Fos) and nerve growth factor (NGF) expression, and assessing voiding function (urodynamically using cystometry). The results revealed that induction of ICH significantly enhanced bladder contraction pressure and time, while simultaneously reducing voiding pressure and time. Furthermore, the c-Fos and NGF expression levels in the neuronal voiding centers were significantly increased in the rats with induced ICH as compared with the control rats. Therefore, this ICH-induced NLUTD rat model may be a more appropriate method to analyze NLUTD in stroke patients than a cerebral infarction model, as the former more accurately reflects the nature of the hemorrhage in the two types of stroke.