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Published Papers 【 display / non-display 】

• Effect of a mobile digital intervention to enhance physical activity in individuals with metabolic disorders on voiding patterns measured by 24-h voided volume monitoring system: Kumejima Digital Health Project (KDHP)

  Miyazato, M; Ashikari, A; Nakamura, K; Nakamura, T; Yamashiro, K; Uema, T; Uehara, M; Masuzaki, H; Saito, S; Maeda, S; Ishida, H; Matsushita, M

  INTERNATIONAL UROLOGY AND NEPHROLOGY ( International Urology and Nephrology )  53 ( 8 ) 1497 - 1505   2021.08 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  PURPOSE: To evaluate the effect of a mobile digital intervention on voiding patterns, we performed 24-h voided volume monitoring in individuals with metabolic disorders. METHODS: Participants with metabolic disorders were grouped into either the intervention group (n = 17), who had access to a smartphone app (CARADA), or the non-intervention group (n = 11), who did not. Urine monitoring was conducted for 24 h using a novel digital self-health monitoring system for urine excretion (s-HMSU). Body weight, abdominal circumference, blood pressure, and biomarkers were measured. RESULTS: Physical findings and blood test results at baseline and 6 months indicated no significant between-group differences. Night-time frequency did not change between baseline and 6 months in the intervention group but significantly worsened at 6 months in the non-intervention group, as compared to baseline (1.0 ± 0.7 vs. 1.5 ± 0.5, p < 0.05). The change in night-time frequency over 6 months did not differ between the intervention and non-intervention groups. Furthermore, the change in hours of undisturbed sleep over 6 months did not differ between the two groups. However, compared with baseline, nocturnal polyuria index tended to worsen at 6 months in the non-intervention group. CONCLUSION: Our study results suggest that mobile digital intervention might be useful for behavioral therapy to improve night-time frequency and urine production and that s-HMSU might be beneficial for confirming the prevention of progress in individuals with metabolic disorders, which can aid in modifying lifestyle.

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• Collagen type 1A1, type 3A1, and LOXL1/4 polymorphisms as risk factors of pelvic organ prolapse

  Ashikari, A; Suda, T; Miyazato, M

  BMC RESEARCH NOTES ( BMC Research Notes )  14 ( 1 ) 15 - 15   2021.01 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  OBJECTIVE: Collagen and elastin are the main components of the female pelvic tissue. We investigated whether single nucleotide polymorphisms (SNPs) of collagen type 1 alpha 1 (COL1A1), collagen type 3 alpha 1 (COL3A1), and lysyl oxidase-like (LOXL) 1 and 4 were associated with the onset of pelvic organ prolapse (POP) in Japanese women. Fifty-two women with POP and 28 women without POP were included. SNPs were identified using the TaqMan® SNP genotyping assay. RESULTS: Age, parity, and lower urinary tract symptoms were significantly higher in the POP group than in the control group. The prevalence of genotypes with rs2862296 polymorphism of LOXL4, an enzyme essential for extracellular matrix remodeling, was different between the POP (26.9% for GG, 51.9% for AG) and control groups (14.8% for GG, 33.3% for AG). However, polymorphisms of COL1A1, COL3A1, and LOXL1 were not related to the onset of POP. In the multivariate logistic regression analysis, age was significantly associated with the occurrence of POP. In the univariate analysis, LOXL4 polymorphism was associated with the onset of POP in Japanese women. The knowledge of acquired risk factors and polymorphisms in the genomic background of patients with POP may help prevent POP via early conservative interventions.

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• Changes in urethral smooth muscle and external urethral sphincter function with age in rats

  Oshiro, T; Kimura, R; Izumi, K; Ashikari, A; Saito, S; Miyazato, M

  PHYSIOLOGICAL REPORTS ( Physiological Reports )  8 ( 24 ) e14643   2021.01 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  To confirm changes in urethral activity with age, both intravesical pressure and urethral perfusion pressure (UPP) were recorded and external urethral sphincter electromyography (EUS-EMG) was performed. A total of 33 female Sprague Dawley rats aged 3 months (young rats), 12 months (middle-aged rats), and 24 months (aged rats) were used. Bladder activity was evaluated using continuous cystometry. Urethral activity was evaluated by simultaneously recording intravesical pressure and UPP in isovolumetric conditions under urethane anesthesia in each group. Additionally, EUS-EMG activity was monitored under the same conditions. In continuous cystometry, the amplitude of bladder contractions was not different among the three groups; nevertheless, residual urine volume was significantly increased in middle-aged and aged rats, as compared in young rats. With respect to UPP, the change in UPP was significantly smaller in aged rats (60%) and middle-aged rats (64%) than in young rats. Furthermore, the mean amplitude of high-frequency oscillations of the EUS was significantly lower in aged (61%) and middle-aged rats (70%) than in young rats. EUS-EMG revealed EUS bursting activity during voiding with clear active and silent phases in young rats but unclear active and silent phases in aged rats. Masson's trichrome staining of the urethra showed EUS atrophy in aged rats compared to young and middle-aged rats. The results indicate that aging induces two urethral dysfunctions in the urethral smooth muscle and EUS, which may lead to dyscoordination between the urinary bladder and urethra.

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• Therapeutic new targets for stress urinary incontinence in the central nervous system

  Miyazato Minoru, Ashikari Asuka

  Folia Pharmacologica Japonica ( The Japanese Pharmacological Society )  155 ( 1 ) 16 - 19   2020

  Type of publication: Research paper (scientific journal)

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  <p>Stress urinary incontinence (SUI) is a common and bothersome problem among middle-aged women. However, there are few useful drugs for SUI. Urethral hypermobility and intrinsic sphincter deficiency are two main causes of SUI. Various animal models of SUI, such as vaginal distention, pudendal nerve injury, or ovariectomy, have been developed to study the pathophysiology of SUI. In addition, we have previously reported that cerebral infarction rats also induce SUI. Leak point pressure measurements are the most commonly used methods to evaluate the urethral dysfunction in SUI animal models. Originally, we have developed microtransducer-tipped catheter measurements of urethral activity during sneezing. Previous or our basic research has clarified potential strategies for pharmacotherapy of SUI in the central nervous system. Therapeutic targets include adrenergic and serotonergic (5-HT) receptors in the spinal cord, which stimulate pudendal nerve innervating the external urethral sphincter and/or sympathetic nerve innervating urethral smooth muscle. Activation of α₁-adrenoceptors, 5-HT_2C, or 5-HT₇ receptors enhances the reflex at the spinal cord level whereas pre- or postsynaptic α₂-adrenoceptors and/or 5-HT_1A receptors inhibit the reflex. We have recently reported that stimulation of the spinal μ-opioid receptors by tramadol also enhances the reflex. Thus, we review the recent advances in basic SUI research and potential targets for pharmacotherapy of SUI in the central nervous system.</p>

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• Validation of a novel digital health monitoring system to measure the volume of voided urine.

  Miyazato M, Yonemoto K, Ashikari A, Saito S, Yamashiro K, Uehara M, Masuzaki H, Ishida H, Matsushita M

  Neurourology and urodynamics ( Neurourology and Urodynamics )  38 ( 4 ) 1106 - 1110   2019.04 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  AIM: To validate a novel digital health monitoring system to measure the volume of voided urine. METHODS: Micturition volume was calculated using our novel digital self-health monitoring system of urine excretion (s-HMSU) in 18 participants (16 women and 2 men; average age, 40.8 years), without a history of voiding symptoms. Participants completed a self-reported questionnaire regarding their medical history and water intake during the period of observation, as well as the Core Lower Urinary Tract Symptom Score (CLSS) questionnaire. To assess the reliability of the voided volumes measured using the s-HMSU, the intraclass correlation coefficient (ICC) was calculated between the volume and the change in body weight before and after micturition. RESULTS: The CLSS questionnaire confirmed the absence of urinary system diseases in all participants. The medical history was also negative with the exception of hypertension in one participant. The ICC (1,1) between the measured volume of urine excretion using the s-HMSU and the change in body weight was 0.972 (95% confidence interval, 0.957-0.982). CONCLUSIONS: The s-HMSU system provides a reliable measure of voiding volume and is appropriate for home use. It has the potential to facilitate large-scale clinical research to examine the relationship between medical diseases and voiding dysfunction.

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Grant-in-Aid for Scientific Research 【 display / non-display 】

Grant-in-Aid for Scientific Research 【 display / non-display 】

• Grant-in-Aid for Scientific Research(C)

  Project Year: 2020.04  -  2023.03 

  Direct: 3,000,000 (YEN)  Overheads: 3,900,000 (YEN)  Total: 900,000 (YEN)

• Grant-in-Aid for Young Scientists(B)

  Project Year: 2017.04  -  2020.03 

  Direct: 3,100,000 (YEN)  Overheads: 930,000 (YEN)  Total: 4,030,000 (YEN)

• Screening for high risk patients of pelvic organ prolapse focused on polymorphisms of collagen and early intervention by pelvic floor rehabilitation

  Grant-in-Aid for Young Scientists(B)

  Project Year: 2017.04  -  2020.03 

  Investigator(s): Ashikari Asuka 

  Direct: 3,100,000 (YEN)  Overheads: 4,030,000 (YEN)  Total: 930,000 (YEN)

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  Cause of pelvic organ prolapse (POP) is well known for acquired risk factor (e.g. parity, age and obesity), however we focused on genetic risk factor of POP that has been reported in European and American populations. Collagen and elastin are main structures of female pelvic tissues. So we investigated whether single nucleotide gene polymorphisms (SNP) of collagen type I alpha 1 (COL1A1), collagen type III alpha 1 (COL3A1) and lysyl oxidase-like (LOXL)-1/4 were associated with the onset of POP in Japanese women. We investigated each genotype of the SNPs by using TaqMan SNP genotyping assay. The polymorphism of LOXL-4, an enzyme which is essential for extracellular matrix remodeling, had relationship to the onset of POP in Japanese women(Odds ratio 3.8-4.5). The knowledge of acquired risk factors and this kind of genomic background in patients with POP would help to improve surgical indications or to prevent POP by earlier conservative interventions.

• The establishment of new system of magnetic stimulation for overactive bladder with age

  Grant-in-Aid for Scientific Research(C)

  Project Year: 2015.04  -  2018.03 

  Investigator(s): Miyazato Minoru, OSHIRO Takuma, ASHIKARI Asuka, KIMURA Ryu 

  Direct: 3,700,000 (YEN)  Overheads: 4,810,000 (YEN)  Total: 1,110,000 (YEN)

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  For the treatment of overactive bladder (OAB), antimuscarinic agents have long been the drug class of choice. However, they can have unpleasant side-effects, such as dry mouth, constipation, headache, blurred vision and tachycardia. In addition, the drugs can also be refractory in some patients with OAB symptoms. Therefore, we aimed to evaluate the efficacy and safety of magnetic stimulation for OAB, as well as stress urinary incontinence, with age. We confirmed restoration of malfunction with OAB by sacral neuromodulation of magnetic stimulation. Thus, magnetic stimulation is useful for urgency incontinence or stress urinary incontinence. In basic research, we confirmed that stimulation of the spinal μ-opioid receptors might be useful for the treatment of stress urinary incontinence in rats.