Role of the angiotensin type 2 receptor gene in congenital anomalies of the kidney and urinary tract, CAKUT, of mice and men.
Angiotensin type 2 receptor gene null mutant mice display congenital anomalies of the kidney and urinary tract (CAKUT). Various features of mouse CAKUT impressively mimic human CAKUT. Studies of the human type 2 receptor (AGTR2) gene in two independent cohorts found that a significant association exists between CAKUT and a nucleotide transition within the lariat branchpoint motif of intron 1, which perturbs AGTR2 mRNA splicing efficiency. AGTR2, therefore, has a significant ontogenic role for the kidney and urinary tract system. Studies revealed that the establishment of CAKUT is preceded by delayed apoptosis of undifferentiated mesenchymal cells surrounding the urinary tract during key ontogenic events, from the ureteral budding to the expansive growth of the kidney and ureter. (+info)
Urinary tract toxicity in rats following administration of beta 3-adrenoceptor agonists.
ZD7114, [(S)-4-[2-(2-hydroxy-3 phenoxypropylamine)ethoxy]-N-(2-methoxyethyl) phenoxyacetamide], and ZD2079, [(R)-N-(2-[4- (carboxymethyl)phenoxy]ethyl)-N-(beta-hydroxyphenethyl)ammonium chloride], are beta 3-adrenoceptor stimulants with selectivity for brown adipose tissue. ZD7144 is the hydrochloride salt of the S-enantiomer of the racemic amide ZD2079. They were developed as potential novel treatments for obesity and non-insulin-dependent diabetes mellitus. Male and female rats were dosed separately by gavage for a minimum of 28 days with 0, 10, 50, and 500 mg/kg/day of ZD7114 or with 0, 10, 30, and 150 mg/kg/day of ZD2079. Two further groups of male and female rats were dosed with 0 and 500 mg/kg/day of ZD7114 for 28 days and were then allowed a 6-wk, undosed withdrawal period. At high doses, both compounds caused urinary tract toxicity, which primarily affected the distal tubules and collecting ducts of the kidney via tubular necrosis. They also caused ureteric inflammation, cystitis, and accumulation of crystalline inclusions throughout the urinary tract. As a result of urinary tract toxicity, affected animals from one or both studies showed reduced red blood cell indices, lower platelet counts, and higher white cell counts. Blood chemistry revealed lower plasma concentrations of glucose (7.28 +/- 1.37 compared to 8.11 +/- 0.65 for the control) and total protein (63.42 +/- 3.65 compared to 69.17 +/- 3.24 for the control) and increased plasma urea (37.15 +/- 19.96 compared to 8.09 +/- 0.87 for the control). Urinalysis showed an increase in the number of crystals, blood, and protein. In the urinary tract, the severe crystalluria with accumulation of crystalline material indicated that this may have a role in the etiology of the target organ toxicity. Poor solubility of the compounds at normal urinary pH was considered a possible mechanism for the crystalluria. (+info)
Significant changes in volume of seminal vesicles as determined by transrectal sonography in relation to age and benign prostatic hyperplasia.
We evaluated the changes in volume of the seminal vesicles as determined by transrectal sonography in terms of the possible relationship with aging, lower urinary tract symptoms and benign prostatic hyperplasia (BPH) in community based populations in Japan. In 641 men (55-86 year, mean 67) on a mass screening program for prostatic diseases, the maximum horizontal area of the seminal vesicles (MHA) was compared with age, American Urological Association (AUA) symptom index scores and transrectal ultrasonic parameters of the prostate including prostatic volume, transition zone (TZ) volume, TZ index and presumed circle area ratio (PCAR). Simple regression analyses demonstrated that MHA correlated significantly with age, prostatic volume, TZ volume, TZ index and PCAR, but not with AUA symptom index scores. Multiple regression analysis revealed age, prostatic volume and PCAR to be independent determinants of MHA. There was a difference in MHA between subjects with BPH (7.1+/-2.5 cm2) and those with a normal prostate (5.6+/-2.1 cm2) with a statistical significance. In the morphological evaluation of the seminal vesicles, the significant influence of age and BPH has to be taken into account. (+info)
Recurrent cystitis in nonpregnant women.
Consistent evidence from RCTs shows that antibiotic prophylaxis (either continuous or postcoital), using trimethoprim TMP-SMZ, nitrofurantoin, or a quinolone, reduces infection rates in women with high rates of recurrent cystitis (at least two per year). Limited evidence suggests that intermittent patient-administered treatment (taken at the onset of symptoms) is an effective alternative management strategy to continuous antibiotic prophylaxis in women with high rates of infection (at least two per year). Limited evidence suggests that long-term prophylaxis is likely to benefit women with a baseline rate of more than two infections per year over many years. However, long-term treatment has not yet been evaluated in RCTs. In women who experience recurrent, uncomplicated cystitis, there is no evidence to support routine investigation of the urinary tract with excretory urography, ultrasonography, cystoscopy, or voiding cystourethrography. No specific subgroups of women who would clearly benefit from investigation have yet been adequately defined. (+info)
Obstruction of the fetal urinary tract.
Understanding the mechanisms of fetal obstructive uropathy will be essential for the specific management of the wide clinical spectrum of congenital obstructive conditions, including selecting observational therapy for mild cases and attempting to maximize renal function in severe cases. Recognition of the unique aspects of fetal renal obstruction is essential to formulate a useful research program, as the lessons of postnatal acquired obstruction are not directly transferable to congenital obstruction. Experimental studies of renal obstruction have demonstrated alterations in the developmental regulation of growth and differentiation in the fetal kidney. Depending on the gestational timing and severity of obstruction, growth may be impaired or accelerated. Similarly, patterns of altered differentiation may indicate immaturity or accelerated maturation, as well as aberrant differentiation. Concomitant with altered development, there is evidence that normal renal regulatory mechanisms, including the renin-angiotensin system and renal hemodynamics, may be affected by obstruction, possibly as compensatory responses. The mechanisms of these various alterations remain to be defined, but are likely to involve combinations of biomechanical signal transduction, growth factor expression, and responses of specific renal autoregulatory mechanisms. Fetal renal obstruction remains incompletely defined. The body of experimental evidence indicates that investigation of mechanisms regulating growth and differentiation is likely to yield important understanding of fetal renal obstruction to permit more accurate prognosis and management. Viewing fetal renal obstruction as a disorder of kidney development, with disordered growth and differentiation, suggests a definition of obstruction as a condition, that--if uncorrected--will lead to impairment in the ultimate functional potential of the kidney. Intervention should aim to maximize functional potential rather than to simply maintain the status quo. (+info)
Evaluation of dysuria in men.
Men with pain or a burning sensation on urination should be evaluated with a thorough history, a focused physical examination and urinalysis (both urine dipstick and microscopic examination of the urine specimen). Although dysuria may be caused by anything that leads to inflammation of the urethal mucosa, it is most often the result of urinary tract infection. In younger patients, the infectious agent is usually a sexually transmitted organism such as Chlamydia trachomatis. In patients over 35 years of age, coliform bacteria predominate. Infection in older men most often occurs as a result of urinary stasis secondary to benign prostatic hyperplasia. Other conditions that may cause dysuria include renal calculus, genitourinary malignancy, spondyloarthropathy and medications. Successful treatment of dysuria depends on correct identification of its cause. (+info)
Evaluation of asymptomatic microscopic hematuria in adults.
In patients without significant urologic symptoms, microscopic hematuria is occasionally detected on routine urinalysis. At present, routine screening of all adults for microscopic hematuria with dipstick testing is not recommended because of the intermittent occurrence of this finding and the low incidence of significant associated urologic disease. However, once asymptomatic microscopic hematuria is discovered, its cause should be investigated with a thorough medical history (including a review of current medications) and a focused physical examination. Laboratory and imaging studies, such as intravenous pyelography, renal ultrasonography or retrograde pyelography, may be required to determine the degree and location of the associated disease process. Cystourethroscopy is performed to complete the evaluation of the lower urinary tract. Microscopic hematuria associated with anticoagulation therapy is frequently precipitated by significant urologic pathology and therefore requires prompt evaluation. (+info)
Vesicoanal, urethroanal, and urethrovesical reflexes initiated by lower urinary tract irritation in the rat.
Irritation of the urinary bladder causes activation of normally "silent" nociceptive primary afferent fibers. In the present study, it is reported that irritation of the urinary bladder or urethra with infusion of 0.5% acetic acid robustly activates motoneurons that innervate the striated muscle of the external anal sphincter via spinal reflex mechanisms. The activation of anal motoneurons following irritation of the bladder and urethra are termed vesicoanal and urethroanal reflexes, respectively. The reflexes can be mimicked by acute application of capsaicin to the bladder and urethra, and they show desensitization following prolonged topical application of capsaicin or following chronic systemic pretreatment with capsaicin. The reflexes can be demonstrated in chronic spinal cord-transected animals, indicating that the reflex pathways are organized within the spinal cord. The urethroanal reflex is also physiologically activated by urethral distension and/or increases in intraluminal pressure. In addition to activation of anal sphincter activity, slight distension, pressure increases, or instillation of 0.5% acetic acid into the urethra inhibited bladder contractions through activation of an inhibitory urethrovesical reflex. These reflexes are discussed in terms of clinical characteristics of urethritis and prostatitis. Anecdotally, it was discovered that the bladder can buffer acetic acid. (+info)