Neural Mechanisms Underlying Lower Urinary Tract Dysfunction

Naoki Yoshimura,Teruyuki Ogawa,Minoru Miyazato,Takeya Kitta,Akira Furuta,Michael B. Chancellor,Pradeep Tyagi 대한비뇨의학회 2014 Investigative and Clinical Urology Vol.55 No.2

This article summarizes anatomical, neurophysiological, and pharmacological studiesin humans and animals to provide insights into the neural circuitry and neurotransmittermechanisms controlling the lower urinary tract and alterations in thesemechanisms in lower urinary tract dysfunction. The functions of the lower urinarytract, to store and periodically release urine, are dependent on the activity of smoothand striated muscles in the bladder, urethra, and external urethral sphincter. Duringurine storage, the outlet is closed and the bladder smooth muscle is quiescent. Whenbladder volume reaches the micturition threshold, activation of a micturition centerin the dorsolateral pons (the pontine micturition center) induces a bladder contractionand a reciprocal relaxation of the urethra, leading to bladder emptying. During voiding,sacral parasympathetic (pelvic) nerves provide an excitatory input (cholinergic and purinergic)to the bladder and inhibitory input (nitrergic) to the urethra. These peripheralsystems are integrated by excitatory and inhibitory regulation at the levels of the spinalcord and the brain. Therefore, injury or diseases of the nervous system, as well as disordersof the peripheral organs, can produce lower urinary tract dysfunction, leadingto lower urinary tract symptoms, including both storage and voiding symptoms, andpelvic pain. Neuroplasticity underlying pathological changes in lower urinary tractfunction is discussed.

Adaptive Noise Reduction Filter for Speech Using Cascaded Sandglass-type Neural Network

Hiroki Yoshimura,Tadaaki Shimizu,Toshie Matumura,Masaya Kimoto,Naoki Isu 대한전자공학회 2008 ITC-CSCC :International Technical Conference on Ci Vol.2008 No.7

In this study, we developed a new adaptive noise reduction filter (CSNNFR: Cascaded Sandglass-type Neural Network Noise Reduction Filter) which is extended from the SNNRF (Sandglass-type Neural Network Noise Reduction Filter). The CSNNRF can perform adaptive noise reduction while capturing dynamic characteristics of the speech signal, owing to the plasticity of the SNN. The CSNNRF is suitable for application to the hearing aid since the ease of hearing the speech signal after noise reduction is more important than the denoising rate. We examined the improvement rate of SN ratio and performed a hearing experiment to evaluate the performance of the CSNNRF as a hearing aid.

Valsalva Aneurysm Filled with Thrombi Mimicking a Cardiac Tumor

Yasuharu Lee,Naoki Mori,Daisuke Nakamura,Takahiro Yoshimura,Masayuki Taniike,Nobuhiko Makino,Hiroyasu Kato,Yasuyuki Egami,Ryu Shutta,Jun Tanouchi,Yoshio Yamada,Masami Nishino 대한심장학회 2012 Korean Circulation Journal Vol.42 No.12

A Valsalva aneurysm filled with thrombi can be difficult to diagnose, because it mimics a cardiac tumor. Both cardiac magnetic resonance imaging (MRI) and transesophageal echocardiogram (TEE) were performed on a patient who showed a low-echoic mass located between the atrial septum and the non-coronary sinus. Based on MRI findings allowing tissue characterization and the accurate location of the mass and the TEE findings of an irregular surface of the mass and a partial defect in the edge of the non-coronary sinus, we diagnosed the mass as a thrombosed Valsalva aneurysm that had perforated the inter-atrial septum. The operative findings coincided with the preoperative di-agnosis. Both MRI and TEE are useful for diagnosing this condition.

Time-Dependent Changes of Urethral Function in Diabetes Mellitus: A Review

Nailong Cao,Baojun Gu,Daisuke Gotoh,Naoki Yoshimura 대한배뇨장애요실금학회 2019 International Neurourology Journal Vol.23 No.2

This article reviewed the current knowledge on time-course manifestation of diabetic urethral dysfunction (DUD), and explored an early intervention target to prevent the contribution of DUD to the progression of diabetes-induced impairment of the lower urinary tract (LUT). In the literature search through PubMed, key words used included “diabetes mellitus,” “diabetic urethral dysfunction,” and “diabetic urethropathy.” Polyuria and hyperglycemia induced by diabetes mellitus (DM) can cause the time-dependent changes in functional and morphological manifestations of DUD. In the early stage, it promotes urethral dysfunction characterized by increased urethral pressure during micturition. However, the detrusor muscle of the bladder tries to compensate for inducing complete voiding by increasing the duration and amplitude of bladder contractions. As the disease progresses, it can induce an impairment of coordinated micturition due to dyssynergic activity of external urethra sphincter, leading to detrusor-sphincter dyssynergia. The impairment of relaxation mechanisms of urethral smooth muscles (USMs) may additionally be attributable to decreased responsiveness to nitric oxide, as well as increased USM responsiveness to α1-adrenergic receptor stimulation. In the late stage, diabetic neuropathy may play an important role in inducing LUT dysfunction, showing that the decompensation of the bladder and urethra, which can cause the decrease of voiding efficiency and the reduced thickness of the urothelium and the atrophy of striated muscle bundles, possibly leading to the vicious cycle of the LUT dysfunction. Further studies to increase our understandings of the functional and molecular mechanisms of DUD are warranted to explore potential targets for therapeutic intervention of DM-induced LUT dysfunction.

Pregnancy outcome in women with inflammatory bowel disease treated with anti-tumor necrosis factor and/or thiopurine therapy: a multicenter study from Japan

( Shunsuke Komoto ),( Satoshi Motoya ),( Yuji Nishiwaki ),( Toshiyuki Matsui ),( Reiko Kunisaki ),( Katsuyoshi Matsuoka ),( Naoki Yoshimura ),( Takashi Kagaya ),( Makoto Naganuma ),( Nobuyuki Hida ),( 대한장연구학회 2016 Intestinal Research Vol.14 No.2

Background/Aims: Anti-tumor necrosis factor drugs (anti-TNF) and thiopurines are important treatment options in patients with inflammatory bowel disease (IBD), including during pregnancy. However, there are limited data on the benefit/risk profile of anti-TNF and thiopurines during pregnancy in Asia. The aim of this study was to analyze pregnancy outcomes of female Japanese IBD patients treated with anti-TNF and/or thiopurines. Methods: This cross-sectional study assessed pregnancy outcomes in 72 women with IBD. Pregnancy outcomes were compared among 31 pregnancies without exposure to infliximab (IFX), adalimumab (ADA), or thiopurines; 24 pregnancies with exposure to anti-TNF treatment (23 IFX, 1 ADA); 7 pregnancies with exposure to thiopurines alone; and 10 pregnancies with exposure to both IFX and thiopurines. Results: Thirty-five of the 41 pregnancies (85.3%) that were exposed to anti-TNF treatment and/or thiopurines resulted in live births after a median gestational period of 38 weeks. Of the 35 live births, 3 involved premature deliveries; 7, low birth weight; and 1, a congenital abnormality. There were 6 spontaneous abortions in pregnancies that were exposed to anti-TNF treatment (17.7%). Pregnancy outcomes among the 4 groups were similar, except for the rate of spontaneous abortions (P =0.037). Conclusions: Exposure to anti-TNF treatment or thiopurines during pregnancy was not related to a higher incidence of adverse pregnancy outcomes in Japanese IBD patients except for spontaneous abortion. (Intest Res 2016;14:139-145)

Current Understanding and Future Perspectives of Interstitial Cystitis/Bladder Pain Syndrome

Tomohiro Ueda,Philip M. Hanno,Ryoichi Saito,Jane M. Meijlink,Naoki Yoshimura 대한배뇨장애요실금학회 2021 International Neurourology Journal Vol.25 No.2

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic disease characterized by suprapubic pain and lower urinary tract symptoms. Perhaps because of the heterogeneous nature of this disease and its multifactorial etiology, clinical trials in allinclusive populations of IC/BPS patients without phenotyping in the last decade have mainly failed to discover new therapeutic modalities of IC/BPS. Thus, phenotyping IC/BPS, aimed at identifying bladder-centric and/or bladder-beyond pathologies, including cystoscopic observation of Hunner or non-Hunner lesions of the bladder mucosa, is particularly important for the future of IC/BPS management. Based on recent discussions at international conferences, including the International Consultation on IC, Japan, it has been proposed that Hunner-lesion IC should be separated from other non-Hunner IC/BPS because of its distinct inflammatory profiles and epithelial denudation compared with non-Hunner IC/BPS. However, there are still no standard criteria for the diagnosis of Hunner lesions other than typical lesions, while conventional cystoscopic observations may miss atypical or small Hunner lesions. Furthermore, diagnosis of the bladder-centric phenotype of IC/BPS requires confirmation that identified mucosal lesions are truly a cause of bladder pain in IC/BPS patients. This review article discusses the current status of IC/BPS pathophysiology and diagnosis, as well as future directions of the proper diagnosis of bladder-centric IC/BPS, in which pathophysiological mechanisms other than those in inflammatory pathways, such as angiogenic and immunogenic abnormalities, could also be involved in both Hunner-lesion IC and non-Hunner IC/BPS. It is hoped that this new paradigm in the pathophysiological evaluation and diagnosis of IC/BPS could lead to pathology-based phenotyping and new treatments for this heterogeneous disease.

Reduction of Bladder Capacity Under Anesthesia Following Multiple Recurrences and Repeated Surgeries of Hunner Lesions in Patients With Interstitial Cystitis

Akira Furuta,Yasuyuki Suzuki,Taro Igarashi,Takahiro Kimura,Shin Egawa,Naoki Yoshimura 대한배뇨장애요실금학회 2022 International Neurourology Journal Vol.26 No.1

Purpose: To investigate the influence of multiple recurrences and repeated surgeries of Hunner lesions on bladder capacity under general anesthesia in patients with interstitial cystitis (IC). Methods: We retrospectively reviewed the clinical records of Hunner-type IC (HIC) patients who underwent transurethral fulguration or resection of Hunner lesions combined with hydrodistension by a single surgeon between 2011 and 2020. Recurrence was defined as reappearance of uncontrolled urinary symptoms in association with new Hunner lesions identified by cystoscopy. Recurrent Hunner lesions were then treated by transurethral surgeries. The recurrence-free rate, potential predictive factors of recurrence, and changes in bladder capacity under anesthesia were examined at each surgical procedure. Results: A total of 92 surgeries were performed in 47 HIC patients, 23 (49%) of whom required multiple procedures (range, 1–5 times). The mean recurrence-free time after the first surgery was 21.7 months. The recurrence-free rate was 53% at 24 months, and decreased to 32% at 48 months. There were no significant differences in age, sex, bladder capacity under anesthesia at the first surgery, duration from symptom onset to the first surgery, O’Leary-Sant questionnaire including symptom and problem indexes, visual analogue scale pain score, and the number of comorbidities between the cases with or without recurrence. Bladder capacity under anesthesia was gradually decreased as the number of surgeries was increased, and bladder capacity at the fourth procedure was significantly decreased to 80% of the capacity at the first surgery. Conclusions: These results suggest that multiple recurrences and repeated surgeries of Hunner lesions result in a reduction of bladder capacity under anesthesia in HIC patients although no predictive factors for recurrence of Hunner lesions were detected

High Prevalence of Dysplastic Development of Sacral Vertebral Arches in Pediatric Enuresis

Hideo Ozawa,Takakuki Shibano,Isao Tanaka,Toshitaka Taniguchi,Michael B. Chancellor,Naoki Yoshimura 대한배뇨장애요실금학회 2023 International Neurourology Journal Vol.27 No.2

Purpose: This is the first report to compare 3-dimensional computed tomography (3D-CT) images between pediatric patients with enuresis and children without lower urinary tract symptoms who underwent pelvic CT for other reasons. Methods: Forty-seven children (33 boys and 14 girls) with primary enuresis underwent 3D-CT of sacrococcygeal bones. The control group consisted of 138 children (78 boys and 60 girls) who underwent pelvic CT for other reasons. First, we determined the presence or absence of unfused sacral arches at the L4-S3 levels in both cohorts. Subsequently, we compared the fusion of sacral arches in age- and sex-matched children from these 2 groups. Results: Dysplastic sacral arches, characterized by lack of fusion at 1 or more levels of the S1–3 arches, were observed in nearly all patients in the enuresis group. In the control group (n=138), 54 of 79 children over 10 years old (68%) exhibited fused sacral arches at 3 S1–3 levels. All 11 control children under 4 years old displayed at least 2 unfused sacral arches at the S1–3 levels. In a comparative study of age- and sex-matched patients with enuresis and control children aged 5 to 13 years (n=32 for each group, with 21 boys and 11 girls; mean age, 8.0±2.2 years [range, 5–13 years]), only 1 patient (3%) in the enuresis group exhibited fusion of all S1–3 arches. In contrast, 20 of 32 control group participants (63%) had 3 fused sacral arches (P<0.0001). Conclusions: Sacral vertebral arches typically fuse by the age of 10 years. However, in this study, children with enuresis exhibited a significantly elevated prevalence of unfused sacral arches, suggesting that dysplastic development of sacral vertebral arches may play a pathological role in enuresis.

Pathophysiology of Overactive Bladder and Pharmacologic Treatments Including β3-Adrenoceptor Agonists -Basic Research Perspectives

Joonbeom Kwon,김덕윤,조강준,Mamoru Hashimoto,Kanako Matsuoka,Tadanobu Kamijo,Zhou Wang,Sergei Karnup,Anne M. Robertson,Pradeep Tyagi,Naoki Yoshimura 대한배뇨장애요실금학회 2024 International Neurourology Journal Vol.28 No.-

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.