The protective arm of the renin -angiotensin system may counteract the intense inflammatory process in fetuses with posterior urethral valves / O braço protetor do sistema renina-angiotensina pode contrapor-se ao intenso processo inflamatório em fetos com válvula de uretra posterior

Abstract Objective: Posterior urethral valve is the most common lower urinary tract obstruction in male children. A high percentage of patients with posterior urethral valve evolve to end‐stage renal disease. Previous studies showed that cytokines, chemokines, and components of the renin-angiotensin system contribute to the renal damage in obstructive uropathies. The authors recently found that urine samples from fetuses with posterior urethral valve have increased levels of inflammatory molecules. The aim of this study was to measure renin-angiotensin system molecules and to investigate their correlation with previously detected inflammatory markers in the same urine samples of fetuses with posterior urethral valve. Methods: Urine samples from 24 fetuses with posterior urethral valve were collected and compared to those from 22 healthy male newborns at the same gestational age (controls). Renin-angiotensin system components levels were measured by enzyme‐linked immunosorbent assay. Results: Fetuses with posterior urethral valve presented increased urinary levels of angiotensin (Ang) I, Ang‐(1‐7) and angiotensin‐converting enzyme 2 in comparison with controls. ACE levels were significantly reduced and Ang II levels were similar in fetuses with posterior urethral valve in comparison with controls. Conclusions: Increased urinary levels of angiotensin‐converting enzyme 2 and of Ang‐(1‐7) in fetuses with posterior urethral valve could represent a regulatory response to the intense inflammatory process triggered by posterior urethral valve.

Resumo Objetivo: A válvula de uretra posterior é a obstrução do trato urinário inferior mais comum em crianças do sexo masculino. Uma alta porcentagem de pacientes com válvula de uretra posterior evolui para doença renal em estágio final. Estudos anteriores mostraram que citocinas, quimiocinas e componentes do sistema renina-angiotensina contribuem para o dano renal em uropatias obstrutivas. Recentemente, descobrimos que amostras de urina de fetos com válvula de uretra posterior tinham níveis aumentados de moléculas inflamatórias. O objetivo deste estudo foi medir as moléculas de renina-angiotensina e investigar sua correlação com marcadores inflamatórios previamente detectados nas mesmas amostras de urina de fetos com válvula de uretra posterior. Métodos: Amostras de urina de 24 fetos com válvula de uretra posterior foram coletadas e comparadas com amostras de urina de 22 recém-nascidos saudáveis de mesma idade gestacional (controles). Os níveis dos componentes de SRA foram medidos por ensaio de imunoabsorção enzimática. Resultados: Os fetos com válvula de uretra posterior apresentaram níveis urinários aumentados de angiotensina (Ang) I, Ang-(1-7) e enzima conversora de angiotensina 2 em comparação com os controles. Os níveis de enzima conversora de angiotensina eram significativamente menores e os níveis de Ang II eram semelhantes nos fetos com válvula de uretra posterior em comparação com os controles. Conclusões: O aumento dos níveis urinários de enzima conversora de angiotensina 2 e de Ang-(1-7) em fetos com válvula de uretra posterior poderia representar uma resposta regulatória ao intenso processo inflamatório desencadeado pela válvula de uretra posterior.

The protective arm of the renin-angiotensin system may counteract the intense inflammatory process in fetuses with posterior urethral valves.

OBJECTIVE: Posterior urethral valve is the most common lower urinary tract obstruction in male children. A high percentage of patients with posterior urethral valve evolve to end-stage renal disease. Previous studies showed that cytokines, chemokines, and components of the renin-angiotensin system contribute to the renal damage in obstructive uropathies. The authors recently found that urine samples from fetuses with posterior urethral valve have increased levels of inflammatory molecules. The aim of this study was to measure renin-angiotensin system molecules and to investigate their correlation with previously detected inflammatory markers in the same urine samples of fetuses with posterior urethral valve. METHODS: Urine samples from 24 fetuses with posterior urethral valve were collected and compared to those from 22 healthy male newborns at the same gestational age (controls). Renin-angiotensin system components levels were measured by enzyme-linked immunosorbent assay. RESULTS: Fetuses with posterior urethral valve presented increased urinary levels of angiotensin (Ang) I, Ang-(1-7) and angiotensin-converting enzyme 2 in comparison with controls. ACE levels were significantly reduced and Ang II levels were similar in fetuses with posterior urethral valve in comparison with controls. CONCLUSIONS: Increased urinary levels of angiotensin-converting enzyme 2 and of Ang-(1-7) in fetuses with posterior urethral valve could represent a regulatory response to the intense inflammatory process triggered by posterior urethral valve.

Allantoic cysts and posterior urethral valves: a case report.

Allantoic cysts are a somewhat rare entity. They are identifiable on antenatal ultrasound examination but are not easily distinguishable from pseudocysts, which are often associated with a poor prognosis. Their etiology remains obscure and obstructive uropathies have been proposed to be one of the underlying mechanisms. We report on a case in which both allantoic cysts and a patent urachus were detected antenatally and turned out to be associated with posterior urethral valves (PUV). The cysts were first seen in the early second trimester, with a full fetal bladder and patent urachus. They disappeared by the 29(th) week. During the subsequent sonographic examinations, the bladder was emptying regularly. The kidneys remained normal throughout the pregnancy. It is hypothesized that the increased pressure within the urinary tract kept the urachus patent, led to the formation of allantoic cysts and, later, to their perforation; this allowed the fetus to empty his bladder and kept him from the usual complications of PUV. This case emphasizes the importance of detection and characterization of umbilical cord cysts on antenatal ultasound examination and suggests that obstructive uropathies should be included in the differential diagnosis of umbilical cord cyst communicating with the fetal bladder.

Benign masses of the female periurethral tissues and anterior vaginal wall.

Due to their rarity, benign masses of the periurethral tissues and anterior vaginal wall are poorly understood. Arriving at the proper evaluation and treatment is challenging because many of these masses have similar presenting signs and symptoms, as well as overlapping differential diagnoses. The literature regarding these lesions mainly consists of level III evidence, mostly involving case reports and series. Clinical management has traditionally been based on established surgical principles and expert opinion. This review presents the pertinent embryologic and anatomic background for these benign masses, as well as other pertinent etiological processes. Furthermore, the most current evidence is reviewed regarding the differential diagnosis, evaluation, and treatment for each mass.

Fetal urinary bladder rupture and urinary ascites secondary to posterior urethral valves. A case report.

Megacystis is a typical prenatal sonographic finding in cases of lower urinary tract obstruction. Urinary bladder perforation represents a rare complication in this condition. We report on a boy with in utero bladder perforation and urinary ascites secondary to posterior urethral valves. The pre- and postnatal therapy is described and the current literature is reviewed.

Normal and abnormal embryonic development of the anorectum in rats.

BACKGROUND: The embryologic and pathologic aspect of anorectal malformation (ARM) remains poorly understood. There is no universally accepted theory to explain anorectal embryology and the abnormal development that produces ARM. The aim of this study was to observe the developmental processes of anorectum in rats and to explore the abnormal embryonic development that leads to ARM. METHODS: Rat embryos with ARM were obtained by treating pregnant rats with administration of ethylenethiourea (ETU). Normal rat embryos and embryos with ARM from gestational days 12.5 to 20 were sectioned serially and sagittally and stained with H & E. The relevant structure including cloaca and urorectal septum (URS) were examined in a temporospatial sequence. RESULTS: Characteristics of anorectum development in ARM rat embryos treated by ETU were as follows: (1) URS never fused with cloaca membrane. (2) Dorsal cloacal membrane was maldeveloped. (3) Cloacal configuration was abnormal. (4) Tail groove never appeared. All type of ARM was the rectourethal fistula and common cloaca in ETU-treated rat embryos and was discernible on gestation day 16. CONCLUSIONS: Absence of the tail groove and maldevelopment of the dorsal cloacal membrane, cloacal configuration, and urorectal septum are likely to be responsible for the formation of ARM. Failure of fusion of the URS with cloacal membrane is the immediate reason for rectourethral fistula or common cloaca in ETU-treated rats.

Development of anorectal malformations using etretinate.

PURPOSE: To investigate the pathogenesis of anorectal malformations (ARM), the authors studied cell proliferation and programmed cell death (apoptosis) patterns in murine embryos that develop ARM as a result of administering an overdose of etretinate, a long-acting vitamin A analogue (retinoid). METHODS: Pregnant mice were fed 60 mg/kg of etretinate on the ninth gestational day (E9). Embryos were obtained between E9.5 and E13, and prepared for histological study. Cell proliferation was examined using proliferative cell-specific nuclear antigen (PCNA) expression. Apoptosis was identified by detecting in situ DNA fragmentation using the TdT-mediated dUTP-digoxigenin nick end-labeling (TUNEL) method. RESULTS: Over 95% of etretinate-treated embryos had ARM including rectoprostatic urethral or rectocloacal fistula. In the histological study, ARM embryos showed defective cell proliferation in the cloacal membrane and excessive apoptosis in the dorsocaudal region on E11, which resulted in a lack of apoptosis in the anal orifice and a short tail on E12, respectively. Cells forming the urorectal septum showed the same pattern of cell proliferation and apoptosis both in ARM embryos and the controls. These results suggest that impairments of embryonal cellular dynamics in the cloacal membrane and dorsocaudal region induce some types of ARM.

Imperforate anus associated with a recto-bulbar-cutaneous fistula.

This is the report of two newborn boys with imperforate anus associated with a long rectocutaneous fistula running deep into the scrotum and communicating, in its midportion, with the bulbar urethra. The findings are compared with those of a somewhat similar case in the literature, with some speculations as to the possible embryogenesis of the lesion.

A hypothesis for the higher incidence of vesico-ureteral reflux and primary megaureters in male babies.

The authors propose a new explanation for the male preponderance in cases with prenatally diagnosed vesico-ureteral reflux and primary megaureters. The theory is based on conclusions drawn from the characteristics of 4 patients (3 perinatal cases and 1 occurring in a 14-year-old boy) presenting with unusual anomalies of the lower urinary tract. In this hypothesis, the male preponderance could be related to an abnormal dilatation of the posterior urethra occurring during the embryological development of the male urethra. The dilatation leads to a flap valve mechanism and to a functional obstruction of the bladder outlet and finally to secondary dilatation of the upper urinary tract. This obstruction may be transitory; reflux and megaureters found in utero or after birth could be considered as sequellae of this phenomenon.

Dorsal urethral diverticulum of the fossa navicularis: symptoms, diagnosis and treatment.

Spotting of blood per urethram, hematuria and episodic painful voiding in boys are not uncommon symptoms, although often the causes are not known. The lacuna magna of the urethra on the glans penis can cause such symptoms, as is demonstrated in this report of 4 cases. Treatment was surgical, which resulted in the immediate cure and relief of symptoms. Our study indicates that radiography of the terminal urethra, probing and endoscopy of the fossa navicularis should be done regularly to determine whether the lacuna magna is the enigma of the symptom complex.

[Congenital recto-urethral fistula. Report of one case without associated anorectal malformation (author's transl)]. / Fistule recto-urétrale congénitale. Rapport d'un cas sans malformation ano-rectale associée.

Report of a case of congenital recto-urethral fistula in a man presenting with sterility. Cure of the fistula after a trans-anal sphincter and trans-anorectal approach of York-Mason without temporary colostomy.

Paraurethral cysts in female neonate.

Paraurethral cysts in the female neonate are uncommon lesions. All reported cases have either ruptured spontaneously or responded to simple marsupialization. However, complete urologic evaluation is mandatory because they simulate ectopic ureteroceles in appearance. Herein is reported our experience with 5 patients. The etiology, embryogenesis, natural history, differential diagnosis, and treatment are discussed.