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      Smooth muscle contractility of laser-enucleated prostate tissues and impacts of preoperative α 1-blocker treatment in patients with and without catheterization

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          Abstract

          Prostate smooth muscle contraction is central in treatment of voiding symptoms in benign prostatic hyperplasia (BPH). Tissues from transurethral resection of the prostate (TURP) and radical prostatectomy (RP) for prostate cancer are widely used to study contractions. However, findings are limited by traumatization in TURP, and uncertain relationship to BPH in RP tissues. This study aims to examine contractions of laser-enucleated tissues. Tissues from holmium/thulium laser enucleation (HoLEP/ThuLEP) and TURP were contracted by KCl, noradrenaline and electric field stimulation (EFS) in an organ bath. Contractions were compared to RP tissues in previous studies. KCl-induced contractions averaged 2.5 mN, 0.7 mN and 3.3 mN in tissues from HoLEP/ThuLEP, TURP and RP, with non-responsive tissues included (2.4% HoLEP/ThuLEP, 37% TURP). Maximum EFS-induced contractions (E max) averaged 47% of KCl in HoLEP/ThuLEP tissues, 27% in TURP tissues, and 68–235% in 21 previous studies with RP tissues. E max values for noradrenaline averaged 99.7% in HoLEP/ThuLEP tissues, 56% in TURP tissues, and ranged from 92 to 260% in RP tissues. Preoperative α 1-blocker treatment reduced EFS- and noradrenaline-induced contractions, and increased EC 50 values for noradrenaline in laser-enucleated, catheterized patients, but not in patients without catheterization. Also, the ex vivo application of α 1-blockers increased the EC 50 values for noradrenaline and reduced E max for EFS. Laser-enucleated tissues allow investigation of prostate smooth muscle contraction in medication-refractory voiding symptoms. Different impacts of preoperative α 1-blocker treatment on ex vivo contractility in tissues from patients with and without catheterization point to clinically relevant heterogeneity of patients undergoing surgery for BPH.

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          Alpha1-, alpha2- and beta-adrenoceptors in the urinary bladder, urethra and prostate.

          1 We have systematically reviewed the presence, functional responses and regulation of alpha(1)-, alpha(2)- and beta-adrenoceptors in the bladder, urethra and prostate, with special emphasis on human tissues and receptor subtypes. 2 Alpha(1)-adrenoceptors are only poorly expressed and play a limited functional role in the detrusor. Alpha(1)-adrenoceptors, particularly their alpha(1A)-subtype, show a more pronounced expression and promote contraction of the bladder neck, urethra and prostate to enhance bladder outlet resistance, particularly in elderly men with enlarged prostates. Alpha(1)-adrenoceptor agonists are important in the treatment of symptoms of benign prostatic hyperplasia, but their beneficial effects may involve receptors within and outside the prostate. 3 Alpha(2)-adrenoceptors, mainly their alpha(2A)-subtype, are expressed in bladder, urethra and prostate. They mediate pre-junctional inhibition of neurotransmitter release and also a weak contractile effect in the urethra of some species, but not humans. Their overall post-junctional function in the lower urinary tract remains largely unclear. 4 Beta-adrenoceptors mediate relaxation of smooth muscle in the bladder, urethra and prostate. The available tools have limited the unequivocal identification of receptor subtypes at the protein and functional levels, but it appears that the beta(3)- and beta(2)-subtypes are important in the human bladder and urethra, respectively. Beta(3)-adrenoceptor agonists are promising drug candidates for the treatment of the overactive bladder. 5 We propose that the overall function of adrenoceptors in the lower urinary tract is to promote urinary continence. Further elucidation of the functional roles of their subtypes will help a better understanding of voiding dysfunction and its treatment.
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            New Author Guidelines for Displaying Data and Reporting Data Analysis and Statistical Methods in Experimental Biology

            The American Society for Pharmacology and Experimental Therapeutics has revised the Instructions to Authors for Drug Metabolism and Disposition, Journal of Pharmacology and Experimental Therapeutics, and Molecular Pharmacology These revisions relate to data analysis (including statistical analysis) and reporting but do not tell investigators how to design and perform their experiments. Their overall focus is on greater granularity in the description of what has been done and found. Key recommendations include the need to differentiate between preplanned, hypothesis-testing, and exploratory experiments or studies; explanations of whether key elements of study design, such as sample size and choice of specific statistical tests, had been specified before any data were obtained or adapted thereafter; and explanations of whether any outliers (data points or entire experiments) were eliminated and when the rules for doing so had been defined. Variability should be described by S.D. or interquartile range, and precision should be described by confidence intervals; S.E. should not be used. P values should be used sparingly; in most cases, reporting differences or ratios (effect sizes) with their confidence intervals will be preferred. Depiction of data in figures should provide as much granularity as possible, e.g., by replacing bar graphs with scatter plots wherever feasible and violin or box-and-whisker plots when not. This editorial explains the revisions and the underlying scientific rationale. We believe that these revised guidelines will lead to a less biased and more transparent reporting of research findings.
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              Combination holmium and Nd:YAG laser ablation of the prostate: initial clinical experience.

              The holmium laser is a recent addition to the urologist's armamentarium, being used primarily for the destruction of urinary calculi. Its use as a tool for ablation of the prostate has not been previously described. Our initial experience with 110 patients who have undergone a combination procedure using the Nd:YAG laser for standard circumferential coagulation followed by holmium laser ablation is reported. A further 32 patients who have had a holmium-only technique are described. In the patients who had the combination technique, the AUA Symptom Score improved from a mean value of 19.8 preoperatively to 7.8 at 3 months. The peak urine flow rate likewise improved, from a mean of 8.9 mL/sec preoperatively to 15.1 mL/sec at 3 months. Only one patient who had the holmium-only technique required recatheterization, compared with nine patients who had the combination procedure. The combination Ho/Nd:YAG laser ablation technique is evolving. The early results of the holmium-only technique suggest an advantage over the combination with regard to catheterization time and degree of irritative symptoms. The longer-term results must be assessed to confirm this impression.
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                Author and article information

                Contributors
                martin.hennenberg@med.uni-muenchen.de
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                10 February 2025
                10 February 2025
                2025
                : 15
                : 4985
                Affiliations
                [1 ]Department of Urology, LMU University Hospital, LMU Munich, ( https://ror.org/05591te55) Munich, Germany
                [2 ]Urologische Klinik Und Poliklinik, ( https://ror.org/00gfym921) Marchioninistr. 15, 81377 München, Germany
                Article
                88884
                10.1038/s41598-025-88884-7
                11811036
                39929919
                fdc3b978-2f23-40e7-b301-296dd5b4b996
                © The Author(s) 2025

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 2 May 2024
                : 31 January 2025
                Funding
                Funded by: Klinikum der Universität München (6933)
                Categories
                Article
                Custom metadata
                © Springer Nature Limited 2025

                Uncategorized
                benign prostatic hyperplasia (bph),prostate smooth muscle,lower urinary tract symptoms (luts),laser enucleation of the prostate,α1-blocker,pharmacology,prostate,benign prostatic hyperplasia,urinary tract obstruction

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