• International Neurourology Journal
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• v.22 no.4
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• pp.275-286
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• 2018

Purpose: OnabotulinumtoxinA (BoNT-A) is a promising therapy for treating neurogenic detrusor overactivity (NDO) in individuals with spinal cord injury (SCI). This systematic review and meta-analysis aimed to carry out an in-depth review and to make an objective estimation of the efficacy and safety of BoNT-A on NDO after SCI. Methods: The PubMed, Embase, and Cochrane databases were searched for all relevant articles published from 2001 to 2016 that referred to NDO, SCI, and BoNT-A or botulinum toxin A. All data were recorded in an Excel spreadsheet by 2 individual reviewers. Review Manager version 5.3 was used to carry out the meta-analysis. Results: This analysis included 17 studies involving 1,455 patients. Compared with placebo and baseline, BoNT-A was effective in increasing maximum cystometric capacity, volume at first involuntary detrusor contraction, cystometric bladder capacity (all P<0.00001), compliance (P=0.001), and the number of patients with complete dryness (P=0.0003), and decreasing detrusor pressure, the number of patients with no involuntary detrusor contractions, the maximum flow rate, the incidence of detrusor overactivity (all P<0.00001), and the number of urinary incontinence episodes (P=0.001). There were no statistically significant differences between doses of 200 U and 300 U or between injections into the detrusor and submucosa. There were no life-threatening adverse events. Conclusions: BoNT-A is effective and safe in treating NDO after SCI. There were no statistically significant differences between doses of 200 U and 300 U or between injecting into the detrusor and submucosa. However, more high-quality randomized controlled trials are still needed.

• International Neurourology Journal
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• v.22 no.4
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• pp.268-274
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• 2018

Purpose: To describe a technique for urodynamic diagnosis of detrusor sphincter dyssynergia (DSD) using urethral pressure measurements and examine potential associations between urethral pressure and bladder physiology among patients with DSD. Methods: Multiple sclerosis (MS) and spinal cord injured (SCI) patients with known DSD diagnosed on videourodynamics (via electromyography or voiding cystourethrography) were retrospectively identified. Data from SCI and MS patients with detrusor overactivity (DO) without DSD were abstracted as control group. Urodynamics tracings were reviewed and urethral pressure DSD was defined based on comparison of DSD and control groups. Results: Seventy-two patients with DSD were identified. Sixty-two (86%) had >20 cm $H_2O$ urethral pressure amplitude during detrusor contraction. By comparison, 5 of 23 (22%) of control group had amplitude of >20 cm $H_2O$ during episode of DO. Mean duration of urethral pressure DSD episode was 66 seconds (range, 10-500 seconds) and mean urethral pressure amplitude was 73 cm $H_2O$ (range, 1-256 cm $H_2O$). Longer (>30 seconds) DSD episodes were significantly associated with male sex (81% vs. 50%, P=0.013) and higher bladder capacity (389 mL vs. 219 mL, P=0.0004). Urethral pressure amplitude measurements during DSD were not associated with significant urodynamic variables or neurologic pathology. Conclusions: Urethral pressure amplitude of >20 cm $H_2O$ during detrusor contraction occurred in 86% of patients with known DSD. Longer DSD episodes were associated with larger bladder capacity. Further studies exploring the relationship between urethral pressure measurements and bladder physiology could phenotype DSD as a measurable variable rather than a categorical observation.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.4
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• pp.439-445
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• 1999

This study is to investigate the mechanism of inhibitory effect of imipramine on the calcium utilization in single cells isolated from canine detrusor. 2 mm thick smooth muscle chops were incubated in 0.12% collagenase solution at $36^{circ}C,$ and aerated with 95% $O_2/5%\;CO_2,$ and then cell suspension was examined. Acetylcholine (ACh) evoked a concentration-dependent contraction of the isolated detrusor cells in normal physiologic salt solution (PSS), and the ACh-induced contraction was significantly inhibited by imipramine. In $Ca^{2+}-free$ PSS, ACh-induced contraction was less than those in normal PSS and it was not affected by the pretreatment with imipramine. $Ca^{2+}-induced$ contraction in $Ca^{2+}-free$ PSS was supressed by imipramine, but addition of A 23187, a calcium ionophore, overcomed the inhibitory effect of imipramine. High potassium-depolarization (40 mM KCl) evoked cell contraction, which was inhibited by imipramine. Caffeine, a releasing agent of the stored $Ca^{2+}$ from sarcoplasmic reticulum, evoked a contraction of the cells that was not blocked by the pretreatment with imipramine. These results suggest that imipramine inhibits the influx of calcium in the detrusor cells through both the receptor-operated- and voltage-gated-calcium channels, but does not affect the release of calcium from intracellular storage site.

• Journal of the Korean Society for Precision Engineering
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• v.29 no.5
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• pp.584-590
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• 2012

The structural and functional disorder of a detrusor induces a bladder hypertrophy and degenerates a bladder muscle gradually by preventing normal urination. Thus, the thickness of the bladder wall has been increased in proportion to the degree of bladder outlet obstruction. In this study, the mechanical characteristics of the detrusor is analyzed for the physical properties and the thickness changes of the bladder muscle using a mathematically analytic method. In order to obtain the mechanical property of the bladder muscle, the tensile test of porcine bladder tissue is performed because its property is similar to that of human. The result of tensile test is applied to the mathematically model as Mooney Rivlin coefficients which represent the hyperelastic material. The model of the bladder is defined as the spherical shape with the initial volume of 50ml. The principal stress and strain according to the thickness are analyzed. Also, computer simulations for three types of the material property for the model of the bladder are performed based on the fact that the stiffness of the bladder is weakened as the progress of the benign prostatic hyperplasia. As a result, the principal stress is 341kPa at the initial thickness of 2.2mm, and is 249kPa at 6.5mm. As the bladder wall thickness increases, the principal stress decreases. The principal stress and strain decrease as the stiffness of the bladder decreases under the same thinkness.

• The Korean Journal of Physiology and Pharmacology
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• v.15 no.3
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• pp.143-147
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• 2011

Defensins, cysteine-rich cationic polypeptides released from neutrophils, are known to have powerful antimicrobial properties. In this study, we sacrificed 30 rats to investigate the effects of ${\alpha}$-defensin 1 on detrusor muscle contractions in isolated rat bladder. From the experiments we found relaxing effects of ${\alpha}$-defensin 1 on the contractions induced by phenylephrine (PE) but not by bethanechol (BCh) in the detrusor smooth muscles. To determine the mechanisms of the effects of ${\alpha}$-defensin 1, the changes of effects on PE-induced contraction by ${\alpha}$-defensin 1 pretreatment were observed after pretreatment of Rho kinase inhibitor (Y-27632), protein kinase C (PKC) inhibitor (Calphostin C), potent activator of PKC (PDBu; phorbol 12,13-dibutyrate), and NF-${\kappa}B$ inhibitors (PDTC; pyrrolidinedithiocarbamate and sulfasalazine). The contractile responses of PE ($10^{-9}{\sim}10^{-4}$ M) were significantly decreased in some concentrations of ${\alpha}$-defensin 1 ($5{\times}10^{-9}$ and $5{\times}10^{-8}$ M). When strips were pretreated with NF-kB inhibitors (PDTC and sulfasalazine; $10^{-7}{\sim}10^{-6}$ M), the relaxing responses by ${\alpha}$-defensin 1 pretreatment were disappeared. The present study demonstrated that ${\alpha}$-defensin 1 has relaxing effects on the contractions of rat detrusor muscles, through NF-${\kappa}B$ pathway. Further studies in vivo are required to clarify whether ${\alpha}$-defensin 1 might be clinically related with bladder dysfunction by inflammation process.

• The Korean Journal of Pharmacology
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• v.31 no.2
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• pp.195-206
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• 1995

The study was undertaken to examine the possibility of the involvement of $K^+$ channels in the mechanism of relaxant-action of imipramine on the isolated canine detrusor muscle strips. Canine urinary bladder were isolated, and smooth muscle strips of 15 mm long and 2 mm wide from the mid-portion of anterior wall were made in the Tyrode solution of $0{\sim}4^{\circ}C$. The strips were prepared for isometric myography in Biancani's isolated muscle chamber containing 1 ml of Tyrode solution, which was maintained with pH 7.4 by aeration with $95%\;O_2/5%CO_2\;at\;37^{\circ}C$. RP 52891, a non-specific $K^+$ channel opener, concentration-dependently suppressed the spontaneous phasic contractions of the detrusor strips. Imipramine, a tricyclic antidepressant, also reduced the spontaneous contractions in a concentration-dependent manner. RP 52891 was more potent than imipramine(p<0.05), and Imipramine was more efficient than RP 52891(p<0.05).Procaine, a voltage-dependent $K^+$ channel blocker, glibenclamide, an ATP-dependent $K^+$ channel blocker, and apamin, a calcium-dependent $K^+$ channel blocker antagonized the relaxant effect of RP 52891, but not of imipramine. Imipramine reduced the electric field stimulation (EFS) -induced contractions concentration-dependently. None of the $K^+$ channel blockers employed for this study, procaine, glibenclamide or apamin antagonized the inhibitory action of imipramine on the EFS-induced contraction. These results suggest that in canine detrusor, the $K^+$ channels of the characteristics of voltage-dependent, ATP-dependent and/or calcium-dependent are exist, and the inhibitory action of imipramine on the contractility of the detrusor is independent from the $K^+$ channels.

• Journal of Yeungnam Medical Science
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• v.12 no.2
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• pp.246-259
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• 1995

This study aimed to investigate the mechanism of action of baclofen on the detrusor muscle isolated from rat. Rats (Sprague-Dawley) were sacrificed by decapitation and exsanguination. Horizontal muscle strips of $2mm{\times}15mm$ were prepared for isometric myography in isolated muscle chamber bubbled with 95% / 5%-$O_2$ / $CO_2$ at $37^{\circ}C$, and the pH was maintained at 7.4. Detrusor strips contracted responding to the electrical field stimulation (EFS) by 2 Hz, 20 msec, monophasic square wave of 60 VDC. The initial peak of EFS-Induced contraction was tended to be suppresed by ${\alpha},{\beta}$-methylene-adenosine 5'-triphosphate (mATP), a partial agonist of purinergic receptor, and baclofen, a $GABA_B$ receptor agonist (statistically nonsignificant). The late sustained contraction by EFS was suppressed significantly (p < 0.05) by additions of atropione, a cholinergic muscarinic receptor antagonist and baclofen. The adenosine 5'-triphosphate-induced contraction was completely abolished by mA TP but not by baclofen. In the presence of atropine, the subsequent addition of acetylcholine could not contract the muscle strips: but the addition of acetylcholine in the presence of baclofen evoked a contraction to a remarkable extent. These results suggest that in the condition of present study, the cholinergic innervation may play a more important role than the purinergic one, and baclofen suppresses the contractility of rat detrusor by the stimulation of the $GABA_B$ receptors to inhibit the release of neurotransmitter from the cholinergic nerve ending.

• Journal of Yeungnam Medical Science
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• v.11 no.2
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• pp.363-374
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• 1994

The purpose of this study was to investigate the characteristics or the potassium channels existing in the rat urinary bladders. Smooth muscle strips of rat detrusor urinae were examined by isometric myography. Relaxation responses of detrusor muscle strips to the three potassium channel openers pinacidil, a cyanoguanidine derivative, BRL 38227, a benzopyran derivative and RP 52891, a tertrahydrothiopyran derivative were examined. The potassium channel openers reduced the basal tone, and the rank order of potency was RP 52891>pincidil>BRL 38227. Procaine, an inhibitor of the voltage-sensitive potassium channel tended to increase the basal tone, but it did not affect the relaxant effects of the calcium-activated potassium channel opener did not antagonize the relaxant effects, but it reduced the Emax of RP 52891 and BRL 38227. Glibenclamide, an inhibitor of the ATP-sensitive potassium channel, antagonized the relaxant effects of pinacidil, RP 52891 and BRL 38227 reducing the Emax of RP 52891 and BRl 38227. Galanin which inhibits secretion of insulin through opening the ATP-sensitive potassium channels in pancreatic ${\beta}$-cells rather increased the basal tone of the isolated detrusor strips. These results suggest that the urinary bladder of the rat has mainly the ATP-sensitive, glibenclamide sensitive potassium channel, which is a different type from that in the pancreatic ${\beta}$-islet cells..

• Journal of Yeungnam Medical Science
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• v.8 no.2
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• pp.138-149
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• 1991

This study was aimed at investigation of the stimulatory innervations on the rat urinary bladder. Detrusor muscle strips of 15 mm long were suspended in isolated muscle chambers containing 1 ml of PSS maintained at $37^{\circ}C$ and aerated with 95% $O_2/5%CO_2$. Isometric myography was perfomed, and the results were as followings : Muscle strips showed "on-contraction" by electric field stimulation (EFS) frequency-dependently. The EFS-induced contraction was not affected by hexamethonium, a ganglion blocker, but abolished, by tetrodotoxin, a nerve conduction blocker. Physostigmine, a cholinesterase inhibitor enhanced the EFS-induced contraction which was inhibited by hemicholinium, an inhibitor of choline uptake at the cholinergic nerve ending. Such an EFS-induced contraction was antagonized by atropine only partially, and the atropine-resistant portion was completely abolished by the desensitization of purinergic receptors by prolonged incubatin of the strips in the presence of high concentratin of ATP. Bethanechol, a cholinergic agonist, elicited concentration-dependent contraction. Adenosine triphosphate (ATP), a purinergic agonist, induced a weak but concentration-dependent contraction of short duration. Bethanechol-induced contraction was not affected by ATP-desensitization, and ATP-induced contraction was not affected by tetrodotoxin. These results suggest that there are at least two main stimulatory components of innervations in the detrusor muscle, cholinergic muscarinic and purinergic ; and those receptors are independent each other.

• The Korean Journal of Physiology
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• v.26 no.2
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• pp.137-141
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• 1992

The present study was aimed at elucidating the mode of inhibitory action of tricyclic antidepressants on the smooth muscle. Effects of amitriptyline on the isolated detrusor muscle strips of the urinary bladder of the rabbit were examined. The spontaneous rhythmic movement of the muscle preparation was frequently observed, which was decreased or abolished by addition of amitriptyline $(10^{-5}{\sim}10^{-3}\;M)$. The muscle preparation responded with contraction dose dependently to carbachol, of which dose response curve shifted to the right in the presence of either amitriptyline or atropine. However, amitriptyline produced a nonparallel shift, whereas atropine caused a parallel one. In calcium free medium, the contraction response to carbachol was markedly decreased, which was resumed by the addition of $CaCl_2$ (2.5mM), but not in the presence of either amitriptyline or nifedipine. KCI (60 mM) produced a potent contraction, which was abolished in the presence of amitriptyline or nifedipine. These results suggest that amitriptyline, unlike atropine, not only acts as a noncompetitive antagonist at cholinergic muscarine receptors but also inhibits Ca-influx through the muscle cell membrane.