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At least 271 records · Page 15Linked to original sources

Extracellular matrix gene responses in a novel ex vivo model of bladder stretch injury.

PURPOSE: Congenital bladder outlet obstruction from either mechanical or functional causes often results in clinical bladder fibrosis. We tested the hypothesis that early molecular changes relevant to fibrosis occur in response to stretch injury of the bladder wall and that specific extracellular matrix receptors mediate some of these responses. Furthermore, we introduce a novel ex vivo model of bladder injury which has advantages over previously described in vivo bladder outlet obstruction models by uniquely interrogating molecular responses to bladder distention. MATERIALS AND METHODS: The bladders of Sprague Dawley rats were hydrodistended transurethrally, the ureters and bladder neck were ligated, and the whole bladder was excised and incubated in culture medium in the distended state. At fixed time-points control and stretch bladders were snap frozen, RNA was extracted, and semiquantitative reverse transcription polymerase chain reaction for collagens I, III and XII, and RHAMM (receptor for hyaluronic acid) messenger (m) RNA was performed to establish trends in stretch related gene expression. Bladder specimens were also subjected to routine histological evaluation. RESULTS: An average 3-fold reduction in collagen I mRNA expression was seen with 8 hours of static stretch (p <0.05). Bladder stretch increased collagen III mRNA levels approximately 2.5-fold (p <0.05). Whole bladder collagen XII and RHAMM mRNA were elevated as much as 5-fold (p <0.05) with stretch. Blocking RHAMM function significantly attenuated these matrix gene responses (p = 0.01 to 0.005). CONCLUSIONS: The ex vivo model of whole bladder stretch is viable and easily reproducible for the study of molecular pathophysiological mechanisms contributing to maladaptive bladder disease. Furthermore, collagen gene transcription is revealed to be rapidly responsive to stretch injury of the bladder. Intact RHAMM receptor function is involved in these responses. Elucidation of the intermediate steps in this response to injury may allow for the development of novel therapeutic strategies which may prevent pathological matrix remodeling seen in clinical bladder disease.

Animals↗

Obstructive primary bladder neck disease: evaluation of the efficacy and safety of alpha1-blockers.

OBJECTIVE: The efficacy and safety of using alpha(1)-adrenergic blockers for treating primary bladder neck obstruction in young and middle-aged men was assessed as the first therapeutic step, before surgery, in a symptomatic non-neurogenic selected group of patients. MATERIALS AND METHODS: From January 1995 to December 2001, primary bladder neck obstruction was diagnosed in 41 men whose average age was 43 years. All of them were evaluated by a complete clinical history, American Urological Association (AUA) symptom score index, physical examination, uroflowmetry, transabdominal ultrasound prostatic volume determination, ultrasound post-void residual determination, videourodynamics including pressure-flow analysis and upper urinary tract screening with renal ultrasound or an excretory urogram. A full daily dose of alpha(1)-adrenergic blockers (alfuzosin or tamsulosin) was administered for at least 6 months. Successful treatment was defined as improved symptoms, voiding diary, maximum flow rate and pressure-flow parameters. Patients who did not gain improvement of symptoms with pharmacological treatment were offered surgery. RESULTS: Overall, pharmacological treatment was successful in 29/41 patients (70.7%) whereas bladder neck endoscopic incision was mandatory in 12/41 (29.3%). CONCLUSIONS: alpha(1)-Blockers were effective and safe for treating young and middle-aged men with symptomatic bladder neck obstruction.

Adrenergic alpha-Antagonists↗

Premalignant epithelial lesions of the gall bladder: a prospective study of 120 cholecystectomy specimens.

One hundred and twenty gall-bladders obtained at cholecystectomy for gall bladder diseases formed the basis of a prospective study of premalignant epithelial lesions. Six cases displayed abnormal mucosa (5%); 4 had atypical hyperplasia (dysplasia) and 2 gall-bladders had carcinoma-in-situ; all were associated with chronic cholecystitis and lithiasis. These changes are considered premalignant and are probably precursors of gall-bladder carcinoma. It is impossible to predict which patient with chronic gall-bladder disease is likely to harbour premalignant epithelial changes. In any event, thorough histological examination of all gall bladders removed surgically is more than justified.

Adult↗

[Percutaneous cystoscopy in dogs and cats].

Cystoscopy enables a reliable diagnosis of urinary bladder diseases. The use of transurethral or perineal endoscopic technique is limited by anatomical features. Therefore it was examined, if the prepubic percutaneous access shows advantages referring to diagnosis and treatment. Using this technique three dogs and two cats were examined. The endoscopic instrumentarium and the technical procedure are described.

Animals↗

Identification of polyamides that enhance adenovirus-mediated gene expression in the urothelium.

Adenovirus-mediated gene therapy of bladder diseases has been limited by the inability to transduce the urothelium successfully using adenoviral vectors. We have sought to identify agents that would increase adenovirus-mediated transgene expression in the bladder. We have utilized a rat model to screen compounds for their ability to enhance viral transgene expression in the rat bladder. Rats received intravesical administration of replication-deficient adenovirus (rAd) formulated in various agents, and transgene expression was evaluated after 48 h by determining the amount of lacZ expression in the luminal epithelium of the bladder. We report the identification of two different polyamides, each capable of dramatically increasing viral transgene expression in the bladder without causing detectable alteration of the umbrella cell layer of the urothelium. We have utilized a carcinogen-induced rat bladder tumor model to demonstrate that these polyamides are also capable of enhancing viral transgene expression in tumor tissue. The identification of these polyamides potentiates the use of adenovirus-mediated gene therapy for the treatment of superficial bladder cancer or other bladder diseases.

Adenoviridae↗