Incontinence in Patients With Underactive Bladder

Karl-Erik Andersson 대한배뇨장애요실금학회 2020 International Neurourology Journal Vol.24 No.3

Current Pharmacologic Approaches in Painful Bladder Research: An Update

Karl-Erik Andersson,Lori Birder 대한배뇨장애요실금학회 2017 International Neurourology Journal Vol.21 No.4

The symptoms of interstitial cystitis (IC)/bladder pain syndrome (BPS) may have multiple causes and involve many contributing factors. Traditional treatments (intravesical instillations) have had a primary focus on the bladder as origin of symptoms without adequately considering the potential influence of other local (pelvic) or systemic factors. Systemic pharmacological treatments have had modest success. A contributing factor to the low efficacy is the lack of phenotyping the patients. Individualized treatment based on is desirable, but further phenotype categorization is needed. There seems to be general agreement that IC is a unique disease and that BPS is a syndrome with multiple pathophysiologies, but this has so far not been not been well reflected in preclinical research with the aim of finding new pharmacological treatments. Current research approaches, including anti-nerve growth factor treatment, anti-tumor necrosis factor-α treatment, activation of SHIP1 (AQX-1125), and P2X3 receptor antagonists, and α1-adrenoceptor antagonists are potential systemic treatments, implying that not only the bladder is exposed to the administered drug, which may be beneficial if the IC/BPS is a bladder manifestation of a systemic disease, or negative (adverse effects) if it is a local bladder condition. Local treatment approaches such as the antagonism of Toll-like receptors (which still is only experimental) and intravesical liposomes (with positive proof-of-concept), may have the advantages of a low number of systemic adverse effects, but cannot be expected to have effects on symptoms generated outside the bladder. Assessment of which of the treatment approaches discussed in this review that can be developed into useful therapies requires further studies.

On the Site and Mechanism of Action of β3-Adrenoceptor Agonists in the Bladder

Karl Erik Andersson 대한배뇨장애요실금학회 2017 International Neurourology Journal Vol.21 No.1

The clinical success of mirabegron as the first β3-adrenoceptor (AR) agonist for treatment of the overactive bladder (OAB) syndrome, has resulted in substantial interest in its site and mechanism of action. Even if the adrenergic innervation of the bladder and urethra has been well studied, the location(s) of β3-ARs in different structures within the bladder wall and urethra, and the mode(s) of action of β3-AR stimulation have still not been established. The recent demonstration of β3-ARs on cholinergic nerve terminals with no immunoreactivity in urothelium or detrusor smooth muscle, is not in agreement with previous morphological studies, and functional data strongly suggest that β3-ARs can be found these structures. However, recent studies suggest that the β3-ARs on detrusor smooth muscle may not be the functionally most relevant. The assumption that β3-AR activation during bladder filling inhibits acetylcholine release from parasympathetic neurons by a prejunctional mechanism and that this decreases bladder micromotions that generate afferent activity, is an attractive hypothesis. It does not exclude that other mechanisms may be contributing, and supports combined approaches to reduce afferent activity for treatment of the OAB syndrome.

Regenerative pharmacology in urology

Karl-Erik Andersson,J Koudy Williams 대한비뇨의학회 2017 Investigative and Clinical Urology Vol.58 No.2

Oxidative Stress and Its Relation to Lower Urinary Tract Symptoms

Karl-Erik Andersson 대한배뇨장애요실금학회 2022 International Neurourology Journal Vol.26 No.4

The aim of this review is to discuss how to link lower urinary tract symptoms (LUTS) and oxidative stress (OS) and to define relevant targets for therapeutic intervention. Narrative review based on published literature. Many of the multifactorial pathophysiological mechanisms behind LUTS can initiate reactive oxygen species (ROS) generation. Assuming that OS is a consequence rather than a primary cause of LUTS it seems reasonable to identify both the disease mechanism initiating LUTS, and the source of ROS involved. There are many possible sources of ROS overproduction, but the NADPH oxidase (NOX) family of enzymes is the primary source; NOX activation in turn, may result in the activation of secondary ROS sources, i.e., ROSdependent ROS production. Selective NOX inhibition therefore seems an attractive therapeutic strategy in LUTS treatment. The finding of NOX2 localization to centers in the brain associated with micturition control, opens up for further studies of NOX involvement in the central control of micturition, normally and in disease. Further information on the localization of the different isoforms of NOX in the LUT e.g., the bladder wall and its components and the prostate, is desirable. To optimize treatment, the pathophysiological mechanism initiating LUTS, and the activated isoform of NOX, should be identified. Unfortunately, in most cases of LUTS this is currently not possible. Even if selective NOX inhibitors have entered the clinical trial stage for treatment of disorders other than LUT dysfunction, their efficacy for LUTS treatment has to be demonstrated. If this can be achieved, an attractive approach would be combination of selective NOX inhibition with established drug therapies.

Drug therapy of overactive bladder - What is coming next?

Karl-Erik Andersson 대한비뇨의학회 2015 Investigative and Clinical Urology Vol.56 No.10

After the approval and introduction of mirabegron, tadalafil, and botulinum toxin A for treatment of lower urinary tract symptoms/overactive bladder, focus of interest has been on their place in therapy versus the previous gold standard, antimuscarinics. However, since these agents also have limitations there has been increasing interest in what is coming next - what is in the pipeline? Despite progress in our knowledge of different factors involved in both peripheral and central modulation of lower urinary tract dysfunction, there are few innovations in the pipe-line. Most developments concern modifications of existing principles (antimuscarinics, β3-receptor agonists, botulinum toxin A). However, there are several new and old targets/drugs of potential interest for further development, such as the purinergic and cannabinoid systems and the different members of the transient receptor potential channel family. However, even if there seems to be good rationale for further development of these principles, further exploration of their involvement in lower urinary tract function/dysfunction is necessary.

Sensor Fusion for Motion Estimation of Mobile Robots with Compensation for Out-of-Sequence Measurements

Karl Berntorp,Karl-Erik °Arz´en,Anders Robertsson 제어로봇시스템학회 2011 제어로봇시스템학회 국제학술대회 논문집 Vol.2011 No.10

The position and orientation estimation problem for mobile robots is approached by fusing measurements from inertial sensors, wheel encoders, and a camera. The sensor fusion approach is based on the standard extended Kalman filter, which is modified to handle measurements from the camera with unknown prior delay. A real-time implementation is done on a four-wheeled omni-directionalmobile robot, using a dynamicmodelwith 11 states. The algorithmis analyzed and validated with simulations and experiments.

Animal Modelling of Interstitial Cystitis/Bladder Pain Syndrome

Lori Birder,Karl-Erik Andersson 대한배뇨장애요실금학회 2018 International Neurourology Journal Vol.22 No.S2

The etiology of interstitial cystitis/bladder pain syndrome (IC/BPS) remains elusive and may involve multiple causes. To better understand its pathophysiology, many efforts have been made to create IC/BPS models. Most existing models of IC/BPS strive to recreate bladder-related features by applying noxious intravesical or systemic stimuli to healthy animals. These models are useful to help understand various mechanisms; however, they are limited to demonstrating how the bladder and nervous system respond to noxious stimuli, and are not representative of the complex interactions and pathophysiology of IC/BPS. To study the various factors that may be relevant for IC/BPS, at least 3 different types of animal models are commonly used: (1) bladder-centric models, (2) models with complex mechanisms, and (3) psychological and physical stressors/natural disease models. It is obvious that all aspects of the human disease cannot be mimicked by a single model. It may be the case that several models, each contributing to a piece of the puzzle, are required to recreate a reasonable picture of the pathophysiology and time course of the disease(s) diagnosed as IC/BPS, and thus to identify reasonable targets for treatment.

Neuropelveology: An Emerging Discipline for the Management of Chronic Pelvic Pain

Marc Possover,Karl Erik Andersson,Axel Forman 대한배뇨장애요실금학회 2017 International Neurourology Journal Vol.21 No.4

Chronic pelvic pain (CPP) is a common condition involving multiple, organ-specific medical specialties, each with its own approach to diagnosis and treatment. Management requires knowledge of the interplay between pelvic organ function and neuro- functional anatomy, and of the neurologic and psychological aspects of CPP, but no current specialty fully encompasses this approach. Neuropelveology is an emerging discipline focusing on pathologies of the pelvic nervous system on a cross-disciplinary basis. It involves a neurological/neurosurgical approach, combining the knowledge required for a proper neurologic diagnosis, confirmation by transvaginal/transrectal examination of the pelvic nerves, and advanced laparoscopic surgery in selected cases of CPP. The management of CPP requires multidisciplinary contributions, and neuropelveology may offer an educational framework for the interdisciplinary exchange of knowledge between clinical physicians and basic researchers.

Persistent detrusor overactivity in rats after relief of partial urethral obstruction

Jin, Long-Hu,Andersson, Karl-Erik,Han, Jeong-Uk,Kwon, Yong-Hyun,Park, Chang-Shin,Shin, Hwa-Yoan,Yoon, Sang-Min,Lee, Tack American Physiological Society 2011 American journal of physiology. Regulatory, integr Vol.301 No.4