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      Structural alterations of the bladder induced by detrusor instability: experimental study in rabbits

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          Abstract

          OBJECTIVES: The aim of this study was to evaluate the histopathological and immunohistochemical alterations induced by detrusor instability in the bladder of rabbits submitted to partial bladder outlet obstruction. MATERIALS AND METHODS: Thirty male Norfolk rabbits were divided into 2 groups, a clinical control and a group with detrusor instability. Urine culture, cystometric study, histopathological and immunohistochemical analysis were performed in all animals prior to surgery (M1) and 4 weeks after-surgery (M2). RESULTS: Partial obstruction (G2) resulted in a 2.5 fold increment (p < 0.05) in bladder weight when compared to control (G1). Four weeks after surgery, 93% of animals in G2 developed cystitis. Partial obstruction resulted in detrusor instability at M2 and bladder capacity was significantly increased (p < 0.05) from M1 to M2. The incidence of mild to moderate mucosal and adventitious fibrosis at M2 was higher in G2 (p < 0.05) when compared to G1. Inflammatory reaction at M2 was statistically higher (p < 0.05) in G2. There was no difference in muscular hypertrophy between M1 and M2 in G1. However, 67% of G2 bladders showed a moderate to intense muscular hypertrophy at M2. Hyperplasia of the epithelium was also increased in G2 when M1 and M2 were compared (p < 0.05). CONCLUSION: Detrusor instability induced by partial bladder outlet obstruction caused significant histopathological and immunohistochemical alterations in the bladder of rabbits.

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          Most cited references31

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          Storage and voiding symptoms: pathophysiologic aspects.

          Lower urinary tract symptoms (LUTS) can be categorized as storage, voiding, and postmicturition symptoms. Although often associated with benign prostatic hyperplasia (BPH), they may also occur in women. This observation, the beneficial effects of alpha-adrenoceptor (AR) antagonists in men with BPH and LUTS, and the frail correlation between LUTS, and prostatic enlargement and/or outflow obstruction have focused interest on the role of extraprostatic alpha-ARs in the pathogenesis of LUTS. It has been suggested that an upregulation of contraction-mediating alpha-ARs and a downregulation of relaxation-mediating beta-ARs can contribute to LUTS generation. However, recent investigations on human bladder tissue could not confirm such a change. Antimuscarinic agents are effective for treatment of the overactive bladder, which is characterized by urge, frequency, urge incontinence, and nocturia (ie, LUTS). This suggests that muscarinic receptors are involved in the pathogenesis of LUTS, and there is recent evidence implicating purinergic receptors. Structural changes in the bladder, such as smooth muscle hypertrophy and connective tissue infiltration, are associated with detrusor overactivity in about 50% to 66% of patients with BPH. However, it is unclear whether this is caused by bladder outlet obstruction because the symptoms may remain in up to 33% of the patients after surgical removal of the obstruction. When outflow obstruction is reversed in rats, there is a subset (20%) that continues to have overactive voiding, despite a reversal of the bladder hypertrophy, suggesting that changes within the central nervous system may be a contributing factor. LUTS can be caused by many, often overlapping, pathophysiologic mechanisms, which may contribute to individual variation in response to treatment.
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            Current concepts in the treatment of disorders of micturition.

            Disorders of micturition may be divided into disturbances of the storage function of the bladder, and disturbances of the emptying function. The main symptoms of disturbances of storage function are frequency, urgency and incontinence. Hyperactivity of the bladder may lead to urge incontinence, and incompetence of the urethral closure mechanism to stress incontinence. There are many drugs available for treating bladder hyperactivity, but their efficacy as judged from controlled clinical trials (when available) is often limited. Bladder contraction in man is mediated by stimulation of muscarinic receptors, and when given parenterally anticholinergic drugs have been shown to depress bladder hyperactivity irrespective of the underlying cause. Clinically, however, treatment of urge incontinence with anticholinergic drugs is often unsatisfactory. Lack of effect of oral treatment and systemic side effects limit the use of available agents. Drugs with "mixed" actions (anticholinergic and 'direct' muscle effects), for example oxybutynin and terodiline, have well-documented efficacy in bladder hyperactivity. Side effects are common with oxybutynin; terodiline seems to be well tolerated. The aim of drug treatment of stress incontinence is to increase outflow resistance. Although there is only limited possibility of improving the condition with drugs, beneficial effects can be obtained in some patients by use of orally active alpha-adrenoceptor agonists (e.g. phenylpropanolamine) and/or oestrogens. The main symptom of disturbed bladder emptying is urinary retention. Drug therapy is aimed at improving the contractile activity of the detrusor or reducing urethral outflow resistance. Drugs used for improving bladder contractility include parasympathomimetic agents, e.g. bethanechol or carbachol, and intravesical instillation of prostaglandins. Although the efficacy of both types of treatment is open to question, bethanechol seems to be widely used. Increased outflow resistance may be seen in patients with parasympathetic decentralization of the lower urinary tract or in patients with benign prostatic hypertrophy. These patients may respond favourably to alpha-adrenoceptor blockers such as phenoxybenzamine or prazosin.
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              Muscarinic receptor subtypes modulating smooth muscle contractility in the urinary bladder

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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                ibju
                International braz j urol
                Int. braz j urol.
                Sociedade Brasileira de Urologia (Rio de Janeiro )
                1677-6119
                December 2005
                : 31
                : 6
                : 579-586
                Affiliations
                [1 ] Universidade Estadual Paulista Brazil
                Article
                S1677-55382005000600012
                10.1590/S1677-55382005000600012
                1b0384ad-7e11-451e-aaf6-8110d71ca411

                http://creativecommons.org/licenses/by/4.0/

                History
                Product

                SciELO Brazil

                Self URI (journal page): http://www.scielo.br/scielo.php?script=sci_serial&pid=1677-5538&lng=en
                Categories
                UROLOGY & NEPHROLOGY

                Urology
                bladder,rabbits,bladder outlet obstruction,histopathology
                Urology
                bladder, rabbits, bladder outlet obstruction, histopathology

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