Exploring the relation between obesity and urinary incontinence: Pathophysiology, clinical implications, and the effect of weight reduction, ICI-RS 2018.

Aims: To evaluate the relationship between obesity and urinary incontinence (UI) and to determine the effect of weight reduction on the severity of incontinence.

Methods: This is a consensus report of the proceedings of a Research Proposal from the annual International Consultation on Incontinence-Research Society, 14 June to 16 June, 2018 (Bristol, UK): "What are the relationships between obesity and UI, and the effects of successful bariatric surgery?"

Results: Obesity is an increasing problem worldwide and is associated with many adverse effects on health and quality of life. From both translational and clinical studies, there is a strong relationship between obesity and the occurrence of UI.

Is testosterone important in LUT function in men and women? ICI-RS 2015.

Aim: This review article is a collaborative report based upon the Authors' presentations and Group discussion on the role of testosterone (T) in the male and female lower urinary tract (LUT) which took place at the 6th International Consultation on Incontinence Research Society's (ICI-RS) annual meeting, in Bristol, UK (September 8-10, 2015).

Methods: It comprises overviews and opinions on both the current state of knowledge of the role of T in LUT function and dysfunction in both sexes.

Results: Results from animal studies suggest that T treatment may be beneficial for disorders of the LUT in women including urinary incontinence and pelvic organ prolapse.

Are we justified in suggesting change to caffeine, alcohol, and carbonated drink intake in lower urinary tract disease? Report from the ICI-RS 2015.

Aims: There is increasing evidence that diet may have a significant role in the development of lower urinary tract symptoms. While fluid intake is known to affect lower urinary tract function the effects of alcohol, caffeine, carbonated drinks, and artificial sweeteners are less well understood and evidence from epidemiological studies is mixed and sometimes contradictory. The aim of this paper is to appraise the available evidence on the effect of caffeine, alcohol, and carbonated drinks on lower urinary tract function and dysfunction in addition to suggesting proposals for further research.

Psychological and Physical Environmental Factors in the Development of Incontinence in Adults and Children: A Comprehensive Review.

The aim of this review was to identify etiological environmental factors related to incontinence in children and adults. A variety of etiological environmental factors for the development of incontinence were identified. In children, these encompass stressful life events and trauma, family dysfunction, parental psychopathology, school-related stressors, toilet or "potty" training, fluid consumption habits, housing conditions, and the availability of toilets.

Path of translational discovery of urological complications of obesity and diabetes.

Diabetes mellitus (DM) is a prevalent chronic disease. Type 1 DM (T1DM) is a metabolic disorder that is characterized by hyperglycemia in the context of absolute lack of insulin, whereas type 2 DM (T2DM) is due to insulin resistance-related relative insulin deficiency. In comparison with T1DM, T2DM is more complex.

Effect of Polyuria on Bladder Function in Diabetics versus Non-Diabetics: An Article Review.

Objectives: To review studies that investigated the role of polyuria on bladder function.

Methods: We performed a search of the English literature through PubMed. We only included animal studies that assessed parameters of bladder function and had compared diabetic and non-diabetic polyuric animals.

Melatonin and Its Role in Lower Urinary Tract Function: An Article Review.

This article reviewed the results of studies done on animals that assessed effects of melatonin on bladder function. Melatonin does not change strip relaxation on its own. However, pre-treatment with melatonin decreases contractile responses induced by phenylephrine, acetylcholine, bethanechol and KCl in a dose-dependent manner.

Do we need to know more about the effects of hormones on lower urinary tract dysfunction? ICI-RS 2014.

This review article reflects the presentations and subsequent discussions during a think tank at the 5th International Consultation on Incontinence Research Society's annual meeting, held in Bristol, UK (September 22-24, 2014). It reviews the current state of knowledge on the role of hormones in lower urinary tract dysfunction (LUTD) and overactive bladder (OAB) and in particular: highlights some specific basic research findings from discussion participants; reviews future research topics; and discusses potential new therapeutic opportunities for LUTD and OAB. The role of the large conductance voltage- and Ca(2+) -activated K(+) (BK) channels, as novel therapeutic targets for OAB was discussed, in particular as recent studies on human detrusor smooth muscle suggest that estradiol exerts a direct non-genomic activation of the BK channels.

Pathophysiology of idiopathic overactive bladder and the success of treatment: a systematic review from ICI-RS 2013.

Aims: To investigate the frequency of phenotype profiling of patients with idiopathic overactive bladder (OAB) syndrome, and to determine the effectiveness of treatment among individuals with different pathophysiologic profiles.

Methods: The electronic databases MEDLINE, EMBASE, Cochrane CENTRAL, Cochrane Database of Systematic Reviews, and CINAHL were searched from January 1, 1980 to August 12, 2013 for interventional randomized controlled treatment trials (RCTs) of idiopathic OAB. Phenotying for pathophysiologies originating in the urothelial/mucosal layer of the bladder, the detrusor muscle cell layer, and the central nervous system were sought.

Urothelial mucosal signaling and the overactive bladder-ICI-RS 2013.

There is abundant evidence that the lower urinary tract (LUT) mucosal layer is involved both in mechanosensory functions that regulate bladder contractile activity and in urethral sensation. Changes to the mucosa can be associated with a number of bladder pathologies. For example, alterations of the urothelium and underlying lamina propria at both the molecular and structural levels have been reported in both patients and animals associated with disorders such as bladder pain syndrome and diabetic cystopathy.

Do we understand any more about bladder interstitial cells?-ICI-RS 2013.

Aims: To present a brief review on discussions from "Do we understand any more about lower urinary tract interstitial cells?" session at the 2013 International Consultation on Incontinence-Research Society (ICI-RS) meeting in Bristol, UK.

Methods: Discussion focused on bladder interstitial cell (IC) subtypes, their localization and characterization, and communication between themselves, the urothelium, and detrusor smooth muscle. The role of ICs in bladder pathologies and new methods for studying ICs were also addressed.

Corticotropin-releasing factor family peptide signaling in feline bladder urothelial cells.

Corticotropin-releasing factor (CRF) plays a central role in the orchestration of behavioral and neuroendocrine responses to stress. The family of CRF-related peptides (CRF and paralogs: urocortin (Ucn)-I, -II, and -III) and associated receptors (CRFR1 and CRFR2) are also expressed in peripheral tissues such as the skin and gastrointestinal tract. Local signaling may exert multiple effects of stress-induced exacerbation of many complex syndromes, including psoriasis and visceral hypersensitivity.

Effect of botulinum toxin A on urothelial-release of ATP and expression of SNARE targets within the urothelium.

Aims: Botulinum neurotoxin serotype A (BoNT/A) has emerged as an effective treatment of urinary bladder overactivity. Intravesical lipotoxin (BoNT/A delivery using liposomes), which may target the urothelium, is effective in blocking acetic acid induced hyperactivity in animals. The objective of this study was to assess the possible site of toxin action within the urothelium.

Impact of diabetes mellitus on bladder uroepithelial cells.

Diabetic bladder dysfunction (DBD), a prevalent complication of diabetes mellitus (DM), is characterized by a broad spectrum of symptoms including urinary urgency, frequency, and incontinence. As DBD is commonly diagnosed late, it is important to understand the chronic impact of DM on bladder tissues. While changes in bladder smooth muscle and innervation have been reported in diabetic patients, the impact of DM on the specialized epithelial lining of the urinary bladder, the urothelium (UT), is largely unknown.

Alterations in the non-neuronal acetylcholine synthesis and release machinery in esophageal epithelium.

Aims: A non-neuronal cholinergic system has been described in epithelial cells including that of the urinary bladder (urothelium) and the upper gastrointestinal tract (esophagus). Epithelial dysfunction has been implicated in the pathophysiology of persistent pain conditions such as painful bladder syndrome as well as functional heartburn. For example, alterations in the ability to synthesize and release acetylcholine may contribute to changes in epithelial sensory and barrier function associated with a number of functional genitourinary and intestinal disorders.

Botulinum neurotoxin serotype A suppresses neurotransmitter release from afferent as well as efferent nerves in the urinary bladder.

Background: Botulinum neurotoxin A (BoNTA), which alleviates overactive bladder symptoms, is thought to act predominantly via the inhibition of transmitter release from parasympathetic nerves. However, actions at other sites such as afferent nerve terminals are possible.

Objective: To evaluate the effects of BoNTA on bladder afferent neuropeptide release and firing.

Cystitis, co-morbid disorders and associated epithelial dysfunction.

Interstitial cystitis (painful bladder syndrome / interstitial cystitis; PBS/IC) is a persistent pain syndrome affecting the urinary bladder with symptoms including urinary frequency, bladder pain and nocturia.(–6) Various animal models have been studied, most of which mimic some aspect of the human condition of interest to the investigator(s). This review will provide examples of various animal models including those incorporating chronic stress, thought to produce features that share similarities to that of PBS/IC patients, whose symptoms are often exacerbated by various stressors.

Sophisticated models and methods for studying neurogenic bladder dysfunction.

Aim: To describe how the use of new and established animal models and methods can generate vital and far reaching experimental data in the study of mechanism underlying neurogenic bladder overactivity.

Methods: Bladder and colonic irradiated mice and those with upper and lower motor neuron lesions were used to study neurogenic bladder overactivity. Methods included cystometry, tension measurements, afferent nerve recordings and optical mapping of action potentials and intracellular Ca(2+) transients.

Diabetic bladder dysfunction: current translational knowledge.

Purpose: Diabetes mellitus, a metabolic disorder caused by an absolute or relative deficiency of insulin, is a debilitating and costly disease with multiple serious complications. Lower urinary tract complications are among the most common complications of diabetes mellitus. The most common, bothersome lower urinary tract complication of diabetes mellitus is diabetic cystopathy or diabetic bladder dysfunction.

New insights into the pharmacology of the bladder.

Purpose Of Review: Pharmacotherapy of a number of bladder disorders has traditionally focused on targeting the 'sensory' component or bladder nerves and the smooth muscle. This review aims to provide an insight into recent (experimental and clinical) developments in mechanisms of existing therapies as well as novel targets.

Recent Findings: Traditionally, sensory signaling in the urinary bladder has been attributed to activation of bladder afferents, but new findings have pointed to the urothelium and interstitial cells as key participants in the transduction of sensory events.

Expression and function of rat urothelial P2Y receptors.

The control and regulation of the lower urinary tract are partly mediated by purinergic signaling. This study investigated the distribution and function of P2Y receptors in the rat urinary bladder. Application of P2Y agonists to rat urothelial cells evoked increases in intracellular calcium; the rank order of agonist potency (pEC(50) +/- SE) was ATP (5.

Non-neuronal acetylcholine and urinary bladder urothelium.

Non-neuronal release of acetylcholine (ACh) has been proposed to play a role in urinary bladder function. These studies investigated the expression and function of the non-neuronal cholinergic system in cultured urothelial cells isolated from the rat urinary bladder. Our findings have revealed that urothelial cells express the high-affinity choline transporter (CHT1) and acetylcholine-synthesizing enzymes, choline acetyltransferase (ChAT) and carnitine acetyltransferase (CarAT).

The hydroosmotic response of frog urinary bladder to serosal hypertonicity is dependent on adenylate cyclase for its maintenance and affected by [Cl-]o changes.

The role of adenylate cyclase (AC) in the maintenance of the hydroosmotic response to serosal hypertonicity (SH) in anuran urinary bladder is disputed. In this study, norepinephrine (NE) significantly reversed the hydroosmotic response of Rana temporaria bladders in hypertonic medium (330 mosmol/kgH2O). The reversal was inhibited by yohimbine but was unaffected by prazosin and propranolol, indicating that NE action was mediated via alpha2-adrenergic receptors.