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Osamu Yamaguchi - One of the best experts on this subject based on the ideXlab platform.

  • involvement of cyclic amp dependent and independent mechanisms in the relaxation of rat Detrusor Muscle via β adrenoceptors
    European Journal of Pharmacology, 2005
    Co-Authors: Hisashi Uchida, Keiichi Shishido, Masanori Nomiya, Osamu Yamaguchi
    Abstract:

    We investigated the cAMP-dependent and -independent mechanisms of relaxation via beta-adrenoceptor in rat Detrusor Muscle with and without pre-contraction. A microdialysis technique was used to measure Detrusor tension and cAMP level on the same Detrusor tissue. In non-contracted tissue, isoproterenol, clenbuterol (beta2-adrenoceptor agonist) and FR165101, ((8S)-8-{[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino}-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)oxy]acetic acid hydrochloride (beta3-adrenoceptor agonist) relaxed Detrusor Muscle and cAMP levels also increased in a concentration dependent manner. SQ22536 (adenylyl cyclase inhibitor) markedly suppressed relaxation, suggesting that beta-adrenoceptor-mediated relaxation may be attributed mainly to cAMP-dependent mechanism. In high K+ pre-contracted tissue, although relaxation advanced in a concentration dependent manner, cAMP production reached a plateau at concentrations of more than 10(-7) M. SQ22536 had only a small inhibitory effect. However, large-conductance, Ca2+-activated K+ (BK(Ca)) channel inhibitors, charybdotoxin and iberiotoxin markedly suppressed relaxation. These results suggest that in addition to cAMP-dependent pathway, BK(Ca) channels are involved in the beta-adrenoceptor agonists-induced relaxation in pre-contracted Detrusor Muscle.

  • β3 adrenoceptors in human Detrusor Muscle
    Urology, 2002
    Co-Authors: Osamu Yamaguchi
    Abstract:

    The Detrusor Muscle contains beta-adrenoceptors (beta-AR), and 2 subtypes-beta1-AR and beta2-AR-have been identified in most species. Although beta2-AR has an important role in Muscle relaxation via activation of adenylate cyclase, evidence suggests that a third subtype, beta3-AR, which is implicated in metabolic functions of endogenous catecholamines, mediates relaxation of human Detrusor Muscle. There is a predominant expression of beta3-AR messenger RNA (mRNA) in human bladder tissue, with 97% of total beta-AR mRNA being represented by the beta3-AR subtype and only 1.5% and 1.4% by the beta1-AR and beta2-AR subtypes, respectively. Functionally, selective beta3-AR agonists relax human isolated Detrusor, whereas selective beta1-AR/beta2-AR agonists do not. Isoproterenol-induced relaxation is inhibited by selective beta3-AR antagonists but not by selective beta1-AR or beta2-AR antagonists. In animal models, beta3-AR agonists increase bladder capacity and have only weak cardiovascular side effects. Although this evidence points toward the clinical utility of beta3-AR agonists as therapy for overactive bladder, clinical trials of beta3-AR agonists identified in animal models as antiobesity agents indicate side effects of tremor and tachycardia. Development of compounds with high selectivity for the human beta3-AR, identified by screening techniques using cell lines transfected with the human beta1-AR, beta2-AR, and beta3-AR genes, may mitigate such problems. Together with the preliminary finding that 49% (21 of 43) of patients with idiopathic Detrusor instability have a tryptophan 64 arginine mutation of the beta3-AR gene, which may be a useful genetic marker, evidence points toward beta3-AR being a therapeutic target for treatment of overactive bladder disorder.

  • expression and possible functional role of the beta 3 adrenoceptor in human and rat Detrusor Muscle
    The Journal of Urology, 1999
    Co-Authors: Takao Fujimura, Kouichi Tamura, Takeshi Tsutsumi, Takao Yamamoto, Keiko Nakamura, Yasushi Koibuchi, Masakazu Kobayashi, Osamu Yamaguchi
    Abstract:

    AbstractPurpose: To investigate the presence of the beta 3-adrenoceptor (beta 3-AR) in human and rat Detrusor Muscle and the usefulness of beta 3-AR agonists as drugs for the treatment of urinary frequency.Materials and Methods: FK175, ethyl [(S)-8-[(R)-2-(3-chlorophenyl)-2 -hydroxyethylamino]-6,7,8,9-tetrahydro-5H-benzocyclohepton-2-yloxy] acetate monohydrochloride monohydrate, was used as a beta 3-AR selective agonist. The expression of beta-AR subtypes (beta 1-, beta 2-, beta 3-AR) mRNA was investigated in rat and human Detrusor Muscle by RT-PCR. beta 3-AR agonist induced cyclic AMP (cAMP) levels were measured in rat Detrusor Muscle strips. The relaxation response produced by a beta 3-AR agonist was measured in a KCl induced tonic contraction model in rat Detrusor Muscle strips. The effect of a beta 3-AR agonist on urinary bladder function was investigated by cystometry using a conscious rat model of urinary frequency.Results: beta 3-AR mRNA was substantially expressed in both rat and human Detrusor mu...

  • evaluation of mrnas encoding muscarinic receptor subtypes in human Detrusor Muscle
    The Journal of Urology, 1996
    Co-Authors: Osamu Yamaguchi, K Shishido, K Tamura, Tomohisa Ogawa, T Fujimura, M Ohtsuka
    Abstract:

    AbstractPurpose: The present study evaluated the muscarinic receptor subtypes corresponding to m1 to m5 genes in human Detrusor Muscle.Materials and Methods: The mRNAs encoding m2 and m3 subtypes were assessed by reverse transcription (RT)-polymerase chain reaction (PCR). The amounts of cDNA synthesized from m2 and m3 mRNAs were measured by using subcloned plasmid DNAs. The distribution of m2 and m3 mRNAs in Detrusor was estimated by comparing the amount of m2 cDNA with that of m3 cDNA.Results: The m2 mRNA:m3 mRNA ratio was 1.06:1.00 in human Detrusor. In the cryostat sections of human Detrusor, the presence of both m2 and m3 mRNAs was confirmed by in situ hybridization. However, the RT-PCR products derived from m1, m4 and m5 subtype mRNAs were not detected.Conclusion: These results suggest that human Detrusor Muscle coexpresses muscarinic m2 and m3 receptors and that the populations of the 2 subtypes are not significantly different.

Emmanuel Chartierkastler - One of the best experts on this subject based on the ideXlab platform.

  • the presence of Detrusor Muscle in the pathological specimen after transurethral resection of primary pt1 bladder tumors and its relationship to operator experience
    Canadian Journal of Urology, 2012
    Co-Authors: M Roupret, Emmanuel Chartierkastler, David R Yates, Justine Varinot, V Phe, Marcolivier Bitker, Eva Comperat
    Abstract:

    Introduction To assess the quality of transurethral resection of bladder tumors (TURBTs) performed by "senior" and "junior" urologists for pT1 tumors in terms of Detrusor Muscle (DM) presence and recurrence rate at 3 month first cystoscopy (RR-FC). Non-Muscle invasive bladder cancer (NMIBC) is a heterogeneous group with differing biological potentials. Tumors invading lamina propria (pT1) have an increased propensity for recurrence and progression. Accurate staging at the time of primary TURBT, including the presence of DM, is crucial to avoid understaging and unnecessary delay in definitive treatment. Materials and methods We analyzed our maintained bladder tumor database (TURBTs from 2002 to 2009) and selected patients diagnosed with pT1 bladder tumors. Data on surgeon status, tumor characteristics (size, TNM stage 2009, grade, DM presence) and RR-FC were retrieved. Surgeons were stratified into "senior" and "junior" according to the years of prior training. Results Of the 340 TURBTs for pT1 tumors, "senior" and "junior" surgeons performed 237 (69.7%) and 103 (30.3%), respectively. Overall, 238 (70%) TURBTs had DM in the specimen, including 175 (73.8%) and 63 (61.3%) for the "senior" and "junior" operators, respectively (p = 0.02). The overall RR-FC was 37.4% (n = 127) and was significantly different for DM presence and DM absence (30.7% versus 52.9%; p = 0.01). On multivariate analysis, tumor recurrence was associated with "junior" operator experience independent of the presence or absence of DM (OR = 2.33 [1.45-3.74]) p = 0.01). Conclusions The presence of DM in a primary TURBT for pT1 NMIBC is directly associated with operator experience, with an associated increased 3 month recurrence rate for "junior" resectionists.

  • histologic features in the urinary bladder wall affected from neurogenic overactivity a comparison of inflammation oedema and fibrosis with and without injection of botulinum toxin type a
    European Urology, 2006
    Co-Authors: E Comperat, Andre Reitz, Annick Delcourt, Frederique Capron, Pierre Denys, Emmanuel Chartierkastler
    Abstract:

    Abstract Objectives To study histological features and morphological differences in bladder wall specimen from patients with and without botulinum toxin A injections and to compare those issues in responders and non-responders to the toxin therapy. Material and methods Bladder wall specimen obtained from cystectomy in 45 patients with neurogenic overactive bladders with and without injection of botulinum toxin A into the Detrusor Muscle for treatment of neurogenic incontinence were evaluated concerning the histological criteria inflammation, oedema and fibrosis of the bladder wall. Results Bladder wall specimen obtained from patients suffering from neurogenic Detrusor overactivity showed important histological alterations. Generally, inflammatory infiltration, oedema and fibrosis of the bladder wall were frequently observed. When comparing specimen from patients who had received botulinum toxin injection to those from patients who had not, there was no difference concerning inflammation and oedema. However, patients who had received botulinum toxin injection showed significantly less fibrosis of the bladder wall than those who had not received the toxin injection ( p Conclusion In our study injection of botulinum toxin into the Detrusor Muscle did not lead to increased fibrotic activity within the bladder wall, on the contrary patients with previous botulinum toxin injection revealed significant less fibrosis than patients without toxin injection.

  • european experience of 200 cases treated with botulinum a toxin injections into the Detrusor Muscle for urinary incontinence due to neurogenic Detrusor overactivity
    European Urology, 2004
    Co-Authors: Andre Reitz, M Stohrer, G Kramer, Giulio Del Popolo, Emmanuel Chartierkastler, Jurgen Pannek, H Burgdorfer, Konrad Gocking, Helmut Madersbacher, S Schumacher
    Abstract:

    Abstract Objectives: To present a comprehensive experience with botulinum-A toxin (BTA) injected into the Detrusor Muscle in patients with spinal cord injuries/diseases causing neurogenic incontinence. Methods: Ten European medical centers provided the results of 231 patients with neurogenic Detrusor overactivity who were treated with BTA. 300units of Botox ® (Allergan Inc.) were injected cystoscopically into the Detrusor Muscle at 30 different locations, while sparing the trigonum. Urinary continence status, concomitant anticholinergic medication use and patient satisfaction were recorded. Key urodynamic parameters (reflex volume, maximum Detrusor pressure during voiding, Detrusor compliance and maximum cystometric bladder capacity) at baseline and at the first and second urodynamic follow-up examinations were analyzed. Results: By the time of the initial (mean 12 weeks after injection) as well as at the second urodynamic follow-up examinations (mean 36 weeks after injection), the mean cystometric bladder capacity ( p p p p Conclusions: This retrospective European multicenter study presents the most extensive experience to date with BTA injections into the Detrusor Muscle to treat neurogenic incontinence due to Detrusor overactivity and confirms that this new treatment is safe and valuable. Significant improvement of bladder function corresponds with continence and the subjective satisfaction indicated by the treated patients.

Matthias Werner - One of the best experts on this subject based on the ideXlab platform.

Russ Chesswilliams - One of the best experts on this subject based on the ideXlab platform.

  • depressed contractile responses to neurokinin a in idiopathic but not neurogenic overactive human Detrusor Muscle
    European Urology, 2006
    Co-Authors: Donna J Sellers, Christopher R. Chapple, Douglas P W Hay, Russ Chesswilliams
    Abstract:

    Objective The role of tachykinins such as neurokinin A in regulating bladder function is unclear, but NK2 receptors seem to mediate contraction in the human bladder and it has been suggested that these peptides may have a role in the pathophysiology of bladder dysfunction. The present study investigates neurokinin receptor-mediated contractility of Detrusor Muscle in the idiopathic overactive and neurogenic overactive bladder and investigates the neurokinin receptor subtypes involved. Methods Human bladder was obtained from patients undergoing cystectomy (normal) or clam cystoplasty (idiopathic overactive) and from patients with spinal injuries (neurogenic overactive). Strips of isolated Detrusor Muscle were mounted in physiological Krebs-bicarbonate solution and cumulative concentration-response curves to 1 nM to 300 μM neurokinin A (NKA) were obtained in the absence and presence of neurokinin receptor antagonists, either the NK2 receptor-selective antagonist SR 48968 or the NK3 receptor-selective antagonist SB 223412. Results NKA evoked concentration-dependent contraction of normal, idiopathic, and neurogenic overactive Detrusor strips. In idiopathic overactive Detrusor Muscle, NKA-induced contraction was significantly reduced relative to normal Detrusor (0.031 ± 0.005 mg/g, n = 11 versus 0.193 ± 0.039 mg/g, n = 7). Sensitivity to the peptide was also significantly (p

  • the role of β3 adrenoceptors in mediating relaxation of porcine Detrusor Muscle
    British Journal of Pharmacology, 2002
    Co-Authors: Christopher R. Chapple, Tomonori Yamanishi, Kosaku Yasuda, Kenichiro Yoshida, Russ Chesswilliams
    Abstract:

    1 b-adrenoceptors mediate relaxation of bladder Detrusor smooth Muscle. This study investigates the contribution of b3-adrenoceptors to relaxation of the pig urinary bladder. 2 Cell membranes were prepared from Detrusor Muscle of the pig bladder dome and competition experiments with [ 3 H]-dihydroalprenolol (DHA), a non-selective b-adrenoceptor antagonist was used as a specific radioligand to determine the presence of b-adrenoceptor subtypes. In functional experiments, isolated Detrusor Muscle strips were used to determine the potency of agonists and the aAnity of antagonists. 3 In competition binding experiments, CGP20712A (b1-adrenoceptor selective) displaced [ 3 H]DHA from a single binding site with a low aAnity. In contrast, displacement data for ICI 118551 (b2-adrenoceptor antagonist) and SR59230A (b3-adrenoceptor antagonist) best fitted a two-site model suggesting a predominant (70%) population of b3-adrenoceptors. 4 In functional studies, isoprenaline and salbutamol (b2-adrenoceptor agonist) relaxed KCl precontracted Muscle strips with high potency (pEC50 7.7 and 7.2, respectively), whilst CGP12177 and BRL37344 (b3-adrenoceptor agonists) had low potency and were partial agonists. CGP20712A and atenolol (b1-adrenoceptor antagonists) antagonised responses with a low aAnity. ICI118551 antagonized responses to isoprenaline and salbutamol with a high aAnity (pKB=7.8 and 8.7, respectively), but the Schild slopes were low suggesting that responses were mediated by more than one b-adrenoceptor. The Schild plot for SR59230A was biphasic, apparent pKB values for 3‐10 nM SR59230A being 8.6 and those for 30 nM‐1mM being 7.7. 5 These data suggest that b3-adrenoceptors are the predominant b-adrenoceptor subtype present in the pig bladder and that b-adrenoceptor mediated responses of this tissue are mediated via both the b2- and b3-adrenoceptor subtypes. British Journal of Pharmacology (2002) 135, 129‐134

  • the minor population of m3 receptors mediate contraction of human Detrusor Muscle in vitro
    Journal of Autonomic Pharmacology, 2001
    Co-Authors: Russ Chesswilliams, Christopher R. Chapple, Tomonori Yamanishi, Kosaku Yasuda, Donna J Sellers
    Abstract:

    1 The objective was to determine the role of muscarinic receptor subtypes in mediating contraction of the human Detrusor smooth Muscle in vitro. 2 Contractile responses of human Detrusor Muscle strips to carbachol were obtained in the absence and presence of a range of muscarinic antagonists (pirenzepine, methoctramine, 4-diphenylacetoxy-N-methyl piperidine methiodide (4-DAMP), tropicamide, oxybutynin and tolterodine). Affinity estimates (pKB values) were calculated for the antagonists and correlated with values at the cloned muscarinic receptor subtypes quoted in the literature. 3 Pirenzepine, methoctramine and tropicamide drugs that have high affinities at M1, M2 and M4-receptors, respectively, all had low affinities on the human Detrusor (pKB values of 6.8, 6.9 and 6.5, respectively), whilst the M3-selective antagonist 4-DAMP had a high affinity (9.5). Schild plots for all four antagonists had slopes of unity indicating an action at a single receptor. Oxybutynin and tolterodine also acted as competitive antagonists with affinity estimates of 7.6 and 8.1, respectively. 4 When the antagonist affinities obtained on the bladder were plotted against the values published for these antagonists at the cloned muscarinic receptor subtypes, the best correlations were obtained for the m3- and m5-muscarinic receptor subtypes. 5 These data suggest that direct contractile responses of the human Detrusor Muscle to muscarinic receptor stimulation in vitro are mediated solely via the M3-muscarinic receptor subtype with no contribution from the major M2-receptor population.

  • m3 muscarinic receptors but not m2 mediate contraction of the porcine Detrusor Muscle in vitro
    Journal of Autonomic Pharmacology, 2000
    Co-Authors: Donna J Sellers, Christopher R. Chapple, Tomonori Yamanishi, Kosaku Yasuda, Caroline Couldwell, Russ Chesswilliams
    Abstract:

    1. The objective of the study was to determine the role of muscarinic receptor subtypes in mediating contraction of the porcine Detrusor smooth Muscle in vitro. 2. Strips of pig Detrusor Muscle were set up in physiological salt solution and the tensions developed by the tissues were recorded. Responses to carbachol were obtained in the absence and presence of a range of muscarinic antagonists (4-DAMP, methoctramine, darifenacin, oxybutynin, tolterodine and pirenzepine). Antagonist affinity values (pKB values) were calculated and compared with those quoted in the literature for these antagonists at each of the muscarinic receptor subtypes. 3. The M3-selective antagonists, 4-DAMP and darifenacin had high affinities (pKB values of 9.4 and 8.6, respectively). Oxybutynin, tolterodine and pirenzepine had affinities of 8.2, 8.1 and 6.8, respectively, whilst the M2-selective agent methoctramine had a relatively low affinity (pKB = 6.1). The rank order of affinities was, therefore, 4-DAMP > darifenacin > oxybutynin > tolterodine > pirenzepine > methoctramine for the pig Detrusor. Correlation of the antagonist affinities obtained on the bladder with those published for these antagonists at the five muscarinic receptor subtypes identified the M3(m3)-receptor as the muscarinic subtype mediating Detrusor contractile responses in vitro. 4. These data suggest that a small population of M3-muscarinic receptors must mediate direct contractile responses of the pig Detrusor Muscle to muscarinic receptor stimulation in vitro.

Murat Akand - One of the best experts on this subject based on the ideXlab platform.

  • quality control indicators for transurethral resection of non Muscle invasive bladder cancer
    Clinical Genitourinary Cancer, 2019
    Co-Authors: Murat Akand, Tim Muilwijk, Yannic Raskin, Maxime De Vrieze, Steven Joniau, Frank Van Der Aa
    Abstract:

    Complete transurethral resection of bladder tumor (TURBT) is the initial procedure of choice for non-Muscle-invasive bladder cancer, but its quality is far from optimal in clinical practice. We evaluated the existing body of evidence substantiating current quality control indicators (QCIs) for TURBT. A literature search was performed using PubMed and Embase, and selected articles were reviewed according to their level of evidence. Disease recurrence and progression were used as the primary end points. No hard evidence supports complete resection as a QCI, but rationally, it is the most important indicator for TURBT. A repeat resection is an important QCI in high-risk disease patients, but evidence suggests that it may not be necessary when Detrusor Muscle is present in the initial resection specimen. The presence of Detrusor Muscle in the resection specimen is a validated QCI for TURBT. Adjuvant intravesical instillation is a scientifically proven QCI. Bladder perforation is a controversial QCI in the existing literature. No evidence indicates the ideal time frame for the initial TURBT; thus, initial therapy in the first 6 weeks after diagnosis is not a good QCI. Three of the 6 proposed QCIs for TURBT are supported by evidence. Our literature analysis indicated the use of complete resection, repeat resection, the presence of Detrusor Muscle, and intravesical instillation are QCIs to minimize recurrence and progression, and increase beneficial outcomes.