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The new flavone derivative REC 15/2053, a compound with spasmolytic activity on the lower urinary tract, was examined for its in vitro interaction with alpha- and beta-noradrenergic receptors, dopaminergic, muscarinic, serotoninergic, and opiate receptors, and calcium-channel binding sites labeled with 1,4-dihydropyridines from normal rat brain. All the investigated receptors are directly or indirectly involved in the nervous control of the lower urinary tract functions. The activity of REC 15/2053 on these receptors was studied in comparison to the most common drugs used in the management of urinary bladder disorders such as flavoxate, emepronium bromide, oxybutynin, terodiline, and imipramine. REC 15/2053 showed only weak binding to [3H]nitrendipine sites (IC50 = 14 microM) and muscarinic receptors (IC50 = 18 microM), whereas flavoxate was slightly active only at muscarinic receptors (IC50 = 12.2 microM). Emepronium bromide, oxybutynin, and terodiline were active only at muscarinic receptors, with IC50 values of 236, 5.4, and 588 nM, respectively. Oxybutynin showed a weak affinity to [3H]nitrendipine binding sites (IC50 = 44.4 microM). Imipramine was active at alpha 1-adrenergic and muscarinic receptors (IC50 = 248 and 653 nM, respectively). The activity of REC 15/2053 at muscarinic receptors and 1,4-dihydropyridine binding sites seems too low to account for its mechanism of action.
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Physical examination, liver function tests, serology tests, autoantibody tests, genetic analysis of the TATA box of the UGT1A1 gene, ultrasonography and CT scan; MRI cholangiography; liver biopsy.
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The purpose of this study was to compare the effect on urodynamic parameters of anticholinergic and musculotropic agents in sham injured and spinal cord injured (SCI) rats. A standard rat SCI model induced by impact trauma was employed. Cystometrograms were performed under urethane anesthesia four weeks after SCI. Bladder capacity and voiding pressure were determined at the point of micturition monitored urodynamically and visually. The effect of oxybutynin chloride (0.01-0.1 mg/kg), propantheline bromide (0.05-0.5 mg/kg) and flavoxate hydrochloride (0.1-1.0 mg/kg) were assessed independently in sham injured and SCI rats (n = 10 in each group). Bladder capacities were 0.6 +/- 0.2 and 7.1 +/- 1.6 ml in sham and SCI rats (p < 0.01), respectively. Maximal filling pressure was 17.5 +/- 5 mmHg in sham and 25 +/- 5 mmHg in SCI rats (p < 0.05). Bladder capacity increased with all three medications. Administration of oxybutynin, propantheline and flavoxate in sham rats resulted in bladder capacities of 0.88 +/- 0.3, 0.71 +/- 0.3 and 0.8 +/- 0.2 ml, respectively (p < 0.01). In SCI rats, these drugs resulted in bladder capacities of 9.8 +/- 1.1, 7.9 +/- 1.3 and 8.8 +/- 2.0 ml, respectively (p < 0.01). No significant change in maximum filling pressure occurred. We conclude that anticholinergic and musculotropic agents caused a similar increase in bladder capacity in both sham and SCI rats. Oxybutynin enhanced bladder capacity more than propantheline or flavoxate.
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Randomised or quasi-randomised trials of bladder training for the treatment of any type of urinary incontinence.
NS-21 is under development for the treatment of urinary frequency and urinary incontinence. The purpose of this study was to investigate the effects of NS-21 and its active metabolite, RCC-36, on lower urinary tract function in an experimental rat model of urinary frequency.
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Injection of carbachol or flavoxate (0.3 microM each) into the RPRF abolished bladder contraction but there was no change after injection of physiological saline or propiverine. Intravenous injection of flavoxate or propiverine (0.1 to 10 mg/kg each) inhibited bladder contraction. Amino acid analysis revealed that injection of carbachol into the RPRF increased glutamate and glycine levels in the lumbosacral cord, while injection of flavoxate into the RPRF or intravenously caused an increase in glycine the lumbosacral cord. Injection of propiverine into the RPRF or intravenously did not influence lumbosacral cord amino acid levels.
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All randomised and quasi-randomised controlled trials comparing anticholinergic drugs with other drugs for the treatment of overactive bladder symptoms. At least one arm of the study used an anticholinergic drug and at least one other arm used a non-anticholinergic drug.
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While there is no evidence to suggest the use of flavoxate in the treatment of OAB, both oxybutynin and propiverine appear efficacious and safe. Propiverine shows a better tolerability profile than oxybutynin. Both drugs improve HRQoL of patients affected by OAB. Profiles of each drug and dosage differ and should be considered in making treatment choices.
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In PV patients, the treatment with NSAI compounds was effective when it was enable to produce multiple positive effects, mainly through TRUS changes.
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The effects of clenbuterol, a selective beta 2-agonist, on isolated smooth muscle preparations from the rabbit bladder body, bladder base and proximal urethra have been investigated. The inhibitory effects on resting tension and acetylcholine- and field stimulation-induced contractions in the bladder body were compared with those of flavoxate, atropine, and verapamil. Clenbuterol (10(-10)-10(-7) M) had a strong, concentration-dependent relaxant effect on resting tension of the bladder body, and the relaxant effect was antagonized by propranolol. However, clenbuterol had little effect on the bladder base or proximal urethra. Isoproterenol, a non-selective beta agonist, gave a similar result, but was less potent than clenbuterol. Flavoxate failed to reduce the resting tension, but rather enhanced the spontaneous rhythmic contraction in a concentration-dependent manner. Atropine had little effect. Verapamil produced a concentration-dependent relaxation in the bladder body. Acetylcholine-induced contraction in the bladder body was completely inhibited by pretreatment with atropine (10(-7) M). Clenbuterol, flavoxate, and verapamil concentration-dependently inhibited acetylcholine-induced contraction. Field stimulation-induced contraction in the bladder body was not completely inhibited by atropine. However, the residual contraction was completely inhibited by tetrodotoxin. Clenbuterol, flavoxate, and verapamil concentration-dependently inhibited field stimulation-induced contraction. The inhibitory effects of clenbuterol and verapamil were antagonized by an application of propranolol and an increase in external Ca, respectively. The data suggest that the selective relaxant effect of clenbuterol on the bladder body is due to beta 2-antagonistic action, resulting in the inhibition of the contractile response to acetylcholine or field stimulation. Also, its response was different from that of the other drugs used.
We searched the Cochrane Incontinence Group trials register (January 2003). The reference lists of relevant articles were searched, and trialists contacted for details of other trials. Date of the most recent search: January 2003.
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To assess the effects of bladder training for the treatment of urinary incontinence.
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Majority of Indian population is dependent on general practitioners (GPs) for medical services at primary care level in India. They are most preferred and considered to be first contact person for medical services at primary care level. But advances in medical science has put more emphasis on specialist culture and average Bachelor of Medicine and Bachelor of Surgery (MBBS) graduates who are working as general physician are gradually feeling themselves less competent because they are less exposed to latest advances in treatment of diseases. Amidst such scenario, Christian Medical College (CMC) has come up with an idea: "The refer less and resolve more initiative". It has started a decentralized 2-year family medicine distance diploma course (Postgraduate Diploma in Family Medicine (PGDFM)) now accredited by Dr. MGR Medical University, Chennai, Tamil Nadu, that trains the GPs to become family medicine specialist.
Two reviewers assessed the identified studies for eligibility and methodological quality and independently extracted data from the included studies. Data analysis was performed using RevMan software (version 4.2.8).
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We assessed 73 reports of 36 potentially relevant trials; 28 reports of ten trials were eligible for inclusion with a total of 1366, predominantly female, participants. Not all participants' with overactive bladder, in five trials had urinary incontinence. Data from five trials with 467 participants, all female, are therefore included in the review. The quality of trials was variable. Few data describing long term follow up are available.Is bladder training better than no bladder training? Data were available for 149 women from two trials comparing bladder training with no bladder training. These described only a limited number of prespecified outcomes, which varied across the two trials. Point estimates of effect favoured bladder training however confidence intervals were wide and no statistically significant differences were found for primary outcome variables.Is bladder training better than other treatments? Only two trials including 125 women compared bladder training with drugs: one with oxybutynin and one with imipramine plus flavoxate. In the former trial the only outcomes demonstrating a statistically significant difference were participant's perception of cure at six months (RR 1.69; 95% CI 1.21 to 2.34) and adverse events (RR 0.03; 95% CI 0.00 to 0.44), both favouring bladder training. In the latter trial participant's perception of cure immediately after treatment just achieved statistical significance (RR 1.50; 95% CI 1.02 to 2.21) favouring bladder training, and this difference was maintained at approximately two months post treatment. One comparison of bladder training with pelvic floor muscle training plus biofeedback included 132 women: none of the differences in the primary outcomes achieved statistical significance.Is combining bladder training with another treatment better than that other treatment alone? One trial compared pelvic floor muscle training plus biofeedback supplemented with bladder training versus pelvic floor muscle training plus biofeedback alone and included 125 women. Of the primary outcomes both participants' perception of improvement and quality of life, both immediately after treatment, achieved statistical significance, favouring the bladder training combined with pelvic floor muscle training and biofeedback group (perception of improvement: RR 1.18; 95% CI 1.01 to 1.39; quality of life: MD -47.20; 95% CI -87.03 to -7.37), this was not sustained at three months.
In sham-operated rats, NS-21 (> or = 50 mg/kg) significantly increased the bladder capacity without significantly decreasing micturition pressure, while RCC-36 (100 mg/kg) significantly increased bladder capacity, and at a dose of > or = 30 mg/kg, also caused a decrease in micturition pressure. This increase in bladder capacity appeared at lower doses of both NS-21 and RCC-36 in the hypogastric nerve-transected rats. Propiverine (100 mg/kg) increased bladder capacity and at > or = 30 mg/kg, decreased micturition pressure in both sham-operated and nerve-transected rats. Oxybutynin (100 mg/kg) and atropine (30 mg/kg) decreased the micturition pressure in both sham-operated and nerve-transected rats without increasing the bladder capacity, while a similar anticholinergic calcium antagonist, terodiline (100 mg/kg) had no effect on bladder capacity in either sham-operated or nerve-transected rats. Flavoxate (500 mg/kg) significantly increased bladder capacity without significantly decreasing micturition pressure in both sham-operated and nerve-transected rats, while 50 mg/kg of verapamil significantly increased bladder capacity without significantly decreasing the micturition pressure in nerve-transected rats.
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A 65-year-old woman with adult Still's disease developed adult respiratory distress syndrome (ARDS), a fatal pulmonary complication. Intravenous administration of cyclophosphamide, 500 mg/d for three days, was much more effective than high doses of corticosteroids in the patient. Interestingly, hypersensitivity to flavoxate hydrochloride seemed to be a precipitating factor, but not a cause, for both a series of characteristic manifestations of adult Still's disease and development of ARDS in our patient. The association of ARDS with adult Still's disease has not yet been reported. Physicians should be aware of this fatal complication in adult Still's disease, especially in the presence of drug hypersensitivities.
Mirabegron, darifenacin, fesoterodine, flavoxate, oxybutynin ER or immediate-release (IR), propiverine, solifenacin, tolterodine ER or IR, and trospium chloride.
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The effects of flavoxate hydrochloride (Bladderon, piperidinoethyl-3-methylflavone-8-carboxylate; hereafter referred as flavoxate) on voltage-dependent nifedipine-sensitive inward Ba(2+) currents in human detrusor myocytes were investigated using a conventional whole-cell patch-clamp. Tension measurement was also performed to study the effects of flavoxate on K(+)-induced contraction in human urinary bladder. Flavoxate caused a concentration-dependent reduction of the K(+)-induced contraction of human urinary bladder. In human detrusor myocytes, flavoxate inhibited the peak amplitude of voltage-dependent nifedipine-sensitive inward Ba(2+) currents in a voltage- and concentration-dependent manner (K(i) = 10 microM), and shifted the steady-state inactivation curve of Ba(2+) currents to the left at a holding potential of -90 mV. Immunohistochemical studies indicated the presence of the alpha(1C) subunit protein, which is a constituent of human L-type Ca(2+) channels (Ca(V)1.2), in the bundles of human detrusor smooth muscle. These results suggest that flavoxate caused muscle relaxation through the inhibition of L-type Ca(2+) channels in human detrusor.
Randomised trials and cross-over trials (blinded and unblinded) that are either placebo-controlled or comparing two or more treatments.