International Neurourology Journal最新文献

Overactive bladder (OAB) is a symptom-based syndrome defined by urinary urgency, frequency, and nocturia with or without urge incontinence. The causative pathology is diverse; including bladder outlet obstruction (BOO), bladder ischemia, aging, metabolic syndrome, psychological stress, affective disorder, urinary microbiome, localized and systemic inflammatory responses, etc. Several hypotheses have been suggested as mechanisms of OAB generation; among them, neurogenic, myogenic, and urothelial mechanisms are well-known hypotheses. Also, a series of local signals called autonomous myogenic contraction, micromotion, or afferent noises, which can occur during bladder filling, may be induced by the leak of acetylcholine (ACh) or urothelial release of adenosine triphosphate (ATP). They can be transmitted to the central nervous system through afferent fibers to trigger coordinated urgency-related detrusor contractions. Antimuscarinics, commonly known to induce smooth muscle relaxation by competitive blockage of muscarinic receptors in the parasympathetic postganglionic nerve, have a minimal effect on detrusor contraction within therapeutic doses. In fact, they have a predominant role in preventing signals in the afferent nerve transmission process. β3-adrenergic receptor (AR) agonists inhibit afferent signals by predominant inhibition of mechanosensitive Aδ-fibers in the normal bladder. However, in pathologic conditions such as spinal cord injury, it seems to inhibit capsaicin-sensitive C-fibers. Particularly, mirabegron, a β3-agonist, prevents ACh release in the BOO-induced detrusor overactivity model by parasympathetic prejunctional mechanisms. A recent study also revealed that vibegron may have 2 mechanisms of action: inhibition of ACh from cholinergic efferent nerves in the detrusor and afferent inhibition via urothelial β3-AR.

Metabolic syndrome (MS) is associated with both cardiovascular and bladder dysfunction. Insulin resistance (IR) and central obesity, in particular, are the main risk factors. In these patients, vicious pathological cycles exacerbate abnormal carbohydrate metabolism and sustain an inflammatory state, with serious implications for both the heart and bladder. Ketone bodies serve as an alternative energy source in this context. They are considered a "super-fuel" because they generate adenosine triphosphate with less oxygen consumption per molecule, thus enhancing metabolic efficiency. Ketone bodies have a positive impact on all components of MS. They aid in weight loss and glycemic control, lower blood pressure, improve lipid profiles, and enhance endothelial function. Additionally, they possess direct anti-inflammatory, antioxidant, and vasodilatory properties. A shared key player in dysfunction of both the heart and bladder dysfunction is the formation of the NLRP3 inflammasome, which ketone bodies inhibit. Interventions that elevate ketone body levels-such as fasting, a ketogenic diet, ketone supplements, and sodium-glucose cotransporter 2 inhibitors-have been shown to directly affect cardiovascular outcomes and improve lower urinary tract symptoms derived from MS. This review explores the pathophysiological basis of the benefits of ketone bodies in cardiac and bladder dysfunction.

Purpose: Bladder outlet obstruction (BOO) commonly causes detrusor overactivity (DO). In this study, a post hoc analysis of previous obtained data, we investigate if DO occurring in initial phases of BOO is associated with changes in urinary adenosine triphosphate (ATP) levels.

Methods: Adult female Wistar rats were submitted to partial BOO (pBOO) or to sham obstruction. Cystometry was performed at 3 or 15 days after pBOO and saline voided was collected for ATP determination. Normality was tested using Shapiro-Wilk test. The mean frequency of voiding contractions (VCs) of the sham-operated animals at 15 days after surgery, plus or minus 3 standard deviations, was used to represent the normal range. Statistical analyses were performed using the chi-square and Mann-Whitney tests.

Results: DO was indicated by a VC frequency greater than or equal to 0.9 VCs/min. DO was observed in 63% of animals at 3 days and in 33% at 15 days following pBOO. ATP levels were significantly higher in rats with DO compared to those without DO.

Conclusion: The DO phenotype, occurring in the initial phases of BOO, is associated with comparatively high urinary ATP levels.

Purpose: Adreno-muscarinic synergy, a supra-additional contractile response to simultaneous application of α-adrenoreceptor and muscarinic receptor agonists, is a feature of several lower urinary tract regions that have dual sympathetic and parasympathetic innervation. We tested the hypothesis that synergy is also a feature of prostate tissue obtained from men with benign prostatic enlargement.

Methods: Isolated tissue strips were dissected from prostate 'chips', collected after transurethral prostate resection procedures for in vitro experiments, to measure isometric tension at 36°C.

Results: Added separately to the superfusate, phenylephrine and carbachol generated contractions with mean pEC50 (-log10EC50) values of 5.36 and 5.58, respectively, although phenylephrine maximal responses were about six-fold greater. In the presence of carbachol, the mean phenylephrine pEC50 was significantly increased to 5.84 and maximal response increased by 28%; overall, a significant synergistic response was demonstrated. The synergistic response was reduced by muscarinic receptor antagonists, most potently by the M3-selective agent 4-DAMP (1,1-dimethyl-4-diphenylacetoxypiperidinium iodide), and less so by M2 and M1-selective inhibitors gallamine and pirenzepine, but with an overall profile indicating M3/M2 mediation of the synergistic response. The magnitude of the synergistic response was variable between prostate chips that provided isolated preparations suggesting regional heterogenicity, although their zonal origin could not be determined.

Conclusion: These experiments show that adreno-muscarinic contractile synergy is a feature of human hyperplastic prostate tissue. This has implications for the use of a combination therapy of α-blockers and anti-muscarinic agent to relieve secondary symptoms associated with benign prostatic hyperplasia, at least in men who can tolerate antimuscarinics without a risk of retention.

Purpose: Nocturia significantly impacts patients' quality of life but remains insufficiently evaluated and treated. The "Sleep C.A.L.M." system categorizes the factors thought to collectively reflect most underlying causes of nocturia (Sleep disorders, Comorbidities, Actions [i.e., modifiable patient behaviors such as excess fluid intake], Lower urinary tract dysfunction, and Medications). The purpose of this study was to assess the association of nocturia with the Sleep C.A.L.M. categories using a nationally representative dataset.

Methods: Retrospective analysis of the National Health and Nutrition Examination Survey from 2013/14-2017/18 cycles was conducted. Pertinent questionnaire, laboratory, dietary, and physical examination data were used to ascertain the presence of Sleep C.A.L.M. categories in adults ≥20 years of age. Nocturia was defined as ≥2 nighttime voids.

Results: A total of 12,274 included subjects were included (51.6% female; median age, 49.0 years [interquartile range, 34.0-62.0 years]; 27.6% nocturia). Among subjects with nocturia, the prevalence of 0, ≥1, and ≥2 Sleep C.A.L.M. categories was 3.5% (95% confidence interval [CI], 2.8%-4.4%), 96.5% (95% CI, 95.6%-97.2%), and 81.2% (95% CI, 78.9%-83.3%), respectively. Compared to those with 0-1 Sleep C.A.L.M. categories, the adjusted odds of nocturia in subjects with 2, 3, and 4-5 Sleep C. A.L.M. categories were 1.77 (95% CI, 1.43-2.21), 2.33 (1.89-2.87), and 3.49 (2.81-4.35), respectively (P<0.001). Similar trends were observed for most age and sex subgroups. When assessed individually, each of the 5 Sleep C.A.L.M. categories were independently associated with greater odds of nocturia, which likewise persisted across multiple age and sex subgroups.

Conclusion: Sleep C.A.L.M. burden is associated with increased odds of nocturia in a dose-dependent fashion, and potentially a relevant means by which to organize the underlying etiologies for nocturia among community-dwelling adults.

Purpose: The prevalence of lower urinary tract symptoms (LUTS), characterized by problems regarding storage and/or voiding of urine, is known to significantly increase with age. Effective communication between the lower urinary tract and the central nervous system (CNS) is essential for the optimal function of this system, and heavily relies on the efficient interaction between the bladder urothelium and the afferent nerve fibers situated in close proximity to the urothelium within the lamina propria.

Methods: We aimed to quantify aging-related differences in the expression of calcitonin gene-related peptide (CGRP, an established marker for sensory nerve fibers) in the trigonal mucosal layers of young (3-4 months) and aged (25-30 months) rats. We evaluated trigonal tissue from 3 animals per age group. Tissue was serially sectioned at 10 μm and stained for CGRP. Images were taken along the full length of the tissue. For each image we computed the total CGRP-positive area (μm2) and the median value for each animal was used for further analysis.

Results: Upon statistical analysis the aged rats show a significantly lower CGRP-positive area compared to young rats (P=0.0049). These results indicate that aging has a negative effect on the area of CGRP-positive signal in the trigone.

Conclusion: The structural and functional integrity of the sensory web in the trigonum of rats is negatively affected by the aging process, potentially leading to impaired communication between the bladder urothelium the CNS. Consequently, these perturbations in the sensory system may contribute to the pathogenesis or exacerbation LUTS.

Purpose: The aim of this study was to explore the mechanisms of central brain action in patients with neurogenic underactive bladder (UAB) treated with intravesical electrical stimulation (IVES).

Methods: We prospectively recruited patients with neurogenic UAB who chose to receive IVES treatment and healthy subjects (HS). At baseline, the following data were obtained: a 72-hour voiding diary; measurements of postvoid residual urine (PVR), voiding efficiency (VE) and first sensation of bladder filling (FS); American Urological Association Symptom Index Quality of Life (AUA-SI-QOL) scores, and functional near-infrared spectroscopy scans of the prefrontal cortex in the voiding stage. All UAB patients were re-evaluated for these indices after completing 4 weeks of IVES. A >50% improvement in PVR was defined as successful IVES treatment. Prefrontal activity was analyzed using the NIRS_KIT software, corrected with the false discovery rate (P<0.05). Statistical analysis was performed using IBM SPSS Statistics ver. 22.0, and P<0.05 was considered statistically significant.

Results: Eighteen UAB patients and 16 HS were included. IVES treatment was successful in 11 UAB patients and failed in 7. The PVR, VE, 24-hour clean intermittent catheterization, FS volume, and AUA-SI-QOL scores of the UAB group significantly improved after successful IVES treatment. BA9 (right dorsolateral prefrontal cortex [DLPFC]) and BA10 (right frontal pole) were significantly activated after successful IVES, and no significant difference was found between the successful group and HS group after IVES. Before IVES, BA10 (right frontal pole) was significantly deactivated in the failed group compared with the successful group.

Conclusion: The possible central mechanism of IVES treatment for neurogenic UAB is that IVES reactivates the right DLPFC and right frontal pole.