Influence of cerebral infarction on both bladder and urethral activities and changes after tramadol administration in rats.

AIMS: We investigated the changes in bladder and urethral function after cerebral infarction (CI) and the influence of tramadol on these functions. METHODS: Twenty-eight female Sprague Dawley rats were divided into normal and CI groups. In the awake condition, metabolic cage study and blood pressure were evaluated. Under urethane anesthesia, the intravenous effect of tramadol (0.01-1 mg/kg), which has both µ-opioid receptor stimulation and inhibition of norepinephrine and serotonin reuptake, on continuous cystometry, and simultaneous measurements of bladder and urethral perfusion pressure (UPP) were recorded. Infarcted lesions were examined by staining with triphenyltetrazolium chloride, a marker of mitochondrial enzyme activity. RESULTS: CI rats showed impaired sympathetic activity with Horner's syndrome and lower blood pressure. In metabolic cage study, urinary frequency during the dark phase was increased in CI rats. On bladder activity, in CI rats, the baseline pressure threshold for inducing bladder contractions was significantly lower (p < 0.01), and the intercontraction interval was prolonged after tramadol administration. On urethral activity, the baseline UPP was significantly lower in CI rats than in normal rats and it did not change after tramadol administration. Residual urine rate was significantly increased in normal rats, but not in CI rats. CI rats showed brain infarction including the cortex and hypothalamus, which is a center of the autonomic nervous system. CONCLUSIONS: CI-induced ischemic brain damage results in impairment of both bladder and urethral functions, in addition to decreased sympathetic activity. Bladder overactivity after CI can be improved by tramadol; however, urethral activity cannot be improved by it.

Concomitant radiotherapy and transarterial chemoembolization reduce skeletal-related events related to bone metastases from renal cell carcinoma.

OBJECTIVES: The purpose of this study was to compare the efficacy of radiotherapy (RT) combined with transcatheter arterial chemoembolization (TACE) with RT alone for the treatment of bone metastases from renal cell carcinoma (RCC). METHODS: We included in this retrospective study 25 RCC patients (28 bone metastases), who were treated with RT at our institution. Patients were divided into two groups: patients treated with RT alone (monotherapy group; n = 17) and those treated with RT combined with TACE (combined therapy group; n = 11). The administered median RT dose was 30 Gy in 10 fractions. Anti-cancer agents used in TACE were cisplatin (median dose, 50 mg) and carboplatin (median dose, 240 mg) for patients with reduced renal function. We evaluated the objective response, post-RT-skeletal-related event (PR-SRE)-free rate, and adverse events associated with treatment for each group. RESULTS: The objective response rates for bone metastases in the monotherapy and combined therapy groups were 33% and 82%, respectively (p = 0.009). The 2-year PR-SRE-free rate in the monotherapy and combined therapy groups was 41.8% and 100%, respectively (p = 0.009). The objective response and PR-SRE-free rates were significantly superior in the combined therapy than in the monotherapy group. There were no significant differences in adverse events or survival between the two groups. CONCLUSION: RT combined with TACE is a promising treatment for bone metastases from RCC, as it results in higher objective response, and PR-SRE-free rates compared with RT alone. KEY POINTS: • Skeletal-related events (SREs) are common in patients with bone metastases from renal cell carcinoma (RCC). • Radiotherapy (RT) provides pain relief in patients with bone metastases from RCC, but rarely achieves objective response. • Combination of RT with transcatheter arterial chemoembolization results in higher objective response and post-RT-SRE-free rates compared with RT alone and is a promising treatment for bone metastases from RCC, as it.

Tadalafil Improves Nocturia and Nocturia-Related Quality of Life in Patients with Benign Prostatic Hyperplasia (KYU-PRO Study).

INTRODUCTION: Tadalafil improves lower urinary tract symptoms (LUTS) including nocturia. However, the effect of tadalafil on the nocturia-related quality of life (QoL) is still unknown. OBJECTIVE: The effects of tadalafil on nocturia and nocturia-related QoL were evaluated prospectively in patients with benign prostatic hyperplasia (BPH) as a multicenter study. METHODS: Eligible men were ≥40 years with nocturia ≥2 and a prostate volume ≥20 mL. Patients were asked to complete a self-report questionnaire on the International Prostate Symptom Score (IPSS), the Nocturia Quality of Life questionnaire (N-QoL) and the International Index of Erectile Function 5 (IIEF5). Urinary frequency volume charts (FVCs) were also evaluated. These measures were evaluated at baseline, and after 4, 8, and 12 weeks of tadalafil administration (5 mg once daily). RESULTS: Thirty-one patients with a mean age of 74 years, a mean prostate volume of 31 mL, and a mean prostate-specific antigen level of 2.8 ng/mL were included. Treatment with tadalafil significantly improved their nocturia after 4 weeks, and these improvements were maintained for the 12-week treatment period. Total N-QoL score in new patients and several N-QoL items (inadequate sleep at night and overall bother) in all patients improved significantly after tadalafil treatment. FVCs revealed a significant improvement in the number of hours of undisturbed sleep (HUS) after treatment with tadalafil. No serious adverse events were observed. CONCLUSIONS: This study indicates that tadalafil 5 mg once daily improves nocturia, nocturia-related QoL, and HUS in BPH patients with nocturia. These results suggest that tadalafil can offer a clinically meaningful treatment option for BPH patients with nocturia.

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

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.

Role of the serotonergic system in urethral continence reflexes during sneezing in rats.

To clarify the role of serotonin (5-HT) in the prevention of stress urinary incontinence (SUI) during sneezing, we investigated the effect of intraperitoneal application of p-chlorophenylalanine (PCPA; a serotonin synthesis inhibitor) and intravenous application of CP-809101 (a 5-HT2C agonist) or LP44 (a 5-HT7 agonist) using female rats, in which the neurally evoked continence reflex during sneezing was examined. Amplitudes of urethral pressure response during sneezing (A-URS), urethral baseline pressure (UBP) at the middle urethra, and sneeze-induced leak point pressure (S-LPP) were measured in normal female adult rats with or without drug administration. PCPA decreased A-URS by 35.1 cmH2O and UBP by 13.3 cmH2O compared with normal rats. In PCPA-administrated rats, CP-809101 increased A-URS by 24.1 cmH2O and UBP by 15.1 cmH2O, and LP44 also increased A-URS by 20.6 cmH2O and UBP by 11.4 cmH2O compared with rats treated with PCPA alone. SUI was observed with S-LPP of 40.1 cmH2O in PCPA-administrated rats, in which CP-809101 and LP44 increased S-LPP by 28.0 and 15.2 cmH2O, respectively, compared with rats treated with PCPA alone. The effects of CP-809101 and LP44 were antagonized by SB-242084 (a selective 5-HT2C antagonist) and SB-269970 (a selective 5-HT7 antagonist), respectively. These results indicate that activation of 5-HT receptors enhances the active urethral closure reflex during sneezing, at least in part via 5-HT2C and 5-HT7 receptors.

The effect of tramadol on sneeze-induced urethral continence reflex through µ-opioid receptors in the spinal cord in rats.

AIMS: We examined the efficacy of tramadol on the urethral reflex during sneezing, as well as the role of µ-opioid receptors in the spinal cord, in rats. METHODS: Forty-one female Sprague-Dawley rats were used. The rats were divided into normal female rats and rats with vaginal distension (VD), which mimics stress urinary incontinence (SUI) in humans. Under urethane anesthesia, the sneeze-induced amplitude of urethral responses (AUR) and baseline pressure (BP) were examined after intravenous injection of tramadol using a microtransducer-tipped catheter in both rat groups. The effect of intrathecal cyprodime, a selective µ-opioid receptor antagonist, following intravenous tramadol injection was examined in normal rats. The tilt leak point pressure (tilt LPP) after intravenous tramadol injection was also evaluated in both groups. RESULTS: In normal rats, tramadol enhanced the AUR and BP by 33.2% and 19.5%, respectively. Tramadol also increased BP by 13.9% in rats with VD, but it did not change AUR. Intrathecal cyprodime alone did not change AUR, but it decreased BP. However, tramadol-provoked increments in AUR were blocked by intrathecal cyprodime, while BP was recovered to the level that it was before administration of cyprodime. Tramadol was associated with a significant elevation in tilt LPP: 24.8% and 19.5% in normal and VD rats, respectively. CONCLUSIONS: These findings suggest that tramadol effectively enhances the AUR at the spinal level and BP peripherally. Therefore, stimulation of the spinal µ-opioid receptors may be useful for the treatment of SUI.

Age-associated urethral dysfunction in urethane-anesthetized rats.

AIMS: We aimed to investigate the age-associated changes in movement coordination between the urinary bladder and the urethra in rats. METHODS: A total of 17 female Sprague-Dawley rats were used. The rats were divided into young (3 months old) and middle-aged (12-15 months old) groups. In both groups, isovolumetric cystometry and urethral perfusion pressure (UPP) measurements were performed under urethane anesthesia. After the rhythmic bladder contractions stabilized, L-arginine, a nitric oxide (NO) substrate (100 mg/kg), was administered intravenously in both groups. Subsequently, N-nitro-L-arginine methyl ester hydrochloride (L-NAME) (50 mg/kg) was injected intravenously to inhibit NO synthase activity in both groups. RESULTS: UPP change, defined as UPP nadir minus baseline UPP, was significantly smaller in middle-aged rats (64%) than in young rats (P < 0.05). The mean amplitude of high-frequency oscillations (HFOs) of the external urethral sphincter was also significantly lower (62%) in middle-aged rats than that in young rats (P < 0.05). Urethral contraction during UPP change was also noted in middle-aged rats. This urethral contraction disappeared after L-arginine administration. UPP nadir during bladder contraction was inhibited by L-NAME in both groups. UPP change was greater in middle-aged rats than in young rats, and 3 out of 9 middle-aged rats showed a detrusor-sphincter dyssynergia pattern after L-NAME. CONCLUSIONS: The results indicated that aging induces dysfunction in movement coordination between the urinary bladder and the urethra. Thus, age-associated urethral dysfunctions may lead to inefficient voiding with increased post-void residual urine volume, which is often observed in elderly populations.

Effects of multiple simulated birth traumas on urethral continence function in rats.

Multiple vaginal parities have been reported to be an important risk factor for stress urinary incontinence (SUI). Simulated birth trauma with single vaginal distention (VD) has been used to induce the SUI condition in animals; however, the effect of multiple simulated birth traumas on the urethral continence function has not been well characterized. Therefore, we examined the effects of multiple VDs on urethral functions in vivo and the changes in gene expressions of several molecules in the urethra using female SD rats, which were divided into three groups; sham, VD-1 (single VD), and VD-3 groups (3 times of VDs every 2 wk). Two weeks after the final VD, leak point pressure (LPP) and urethral responses during sneezing were evaluated. Also, changes in mRNA levels of urethral molecules were quantified with RT-PCR.　The VD-1 group did not show any change in LPP with only a tendency of decrease in amplitudes of the urethral responses during sneezing (A-URS); however, the VD-3 group showed a significant decrease in LPP and urethral responses such as baseline urethral pressure and A-URS accompanied with SUI episodes during sneezing. Nicotinic receptor subtypes and transforming growth factor (TGF)-ß1 were significantly increased in both VD-1 and VD-3 groups while TNF receptor (TNFR)-1, IL-6, collagens, and matrix metalloproteinases-9 were significantly increased only in the VD-3 group.　These data indicate that rats with multiple simulated birth traumas exhibit profound impairment of the urethral continence function and that these functional changes are associated with those in cytokines, extracellular matrix molecules, and nicotinic receptor subtypes in the urethra.

Effect of continuous positive airway pressure on nocturnal urine production in patients with obstructive sleep apnea syndrome.

AIM: The aim of this study was to identify the clinical features of patients with obstructive sleep apnea syndrome (OSAS) and investigate the impact of continuous positive airway pressure (CPAP) treatment on nocturnal urine volume. MATERIALS AND METHODS: This study enrolled 53 patients with moderate-to-severe OSAS and an apnea-hypoxia index of >20/hr. Data were collected on serum brain natriuretic peptide (BNP) level, International Prostate Symptom Score-Quality of Life (IPSS-QOL) score, Overactive Bladder Symptom Score (OABSS), International Consultation on Incontinence Modular Questionnaire-Nocturia QOL (ICIQ-NQOL) score, Epworth Sleepiness Scale (ESS) score, and the frequency volume chart. Only patients who continued CPAP treatment for 3 months were included in the analysis. RESULTS: In total, 40 patients (33 men and 7 women) completed the study (75.5%). The mean age was 56.9 years. The night-time frequency to void was significantly decreased from 2.1 to 1.2 after CPAP treatment (P < 0.01). The mean scores as assessed by ESS, IPSS-QOL, OABSS, and ICIQ-NQOL significantly improved after CPAP (P < 0.01). The mean diastolic blood pressure significantly decreased after CPAP treatment. However, there was no significant change in the BNP level before and after CPAP treatment. In the frequency volume chart, hours of undisturbed sleep, total nocturnal voided volume, and nocturnal polyuria index significantly improved after CPAP treatment (P < 0.05). However, 24-hr voided volume and mean voided volume during night-time did not change after CPAP treatment. CONCLUSION: CPAP treatment decreases night-time urinary frequency by reducing nocturnal urine production and improves QOL in patients with OSAS. Neurourol. Urodynam. 36:376-379, 2017. © 2015 Wiley Periodicals, Inc.

A questionnaire survey to assess lower urinary tract symptoms in patients with chronic stroke.

OBJECTIVES: In this study, we evaluated the prevalence of lower urinary tract symptoms and the associated clinical features in patients with chronic stroke. METHODS: Patients with stroke who had been regularly followed up at general medical hospitals in Okinawa, Japan were enrolled in the study. The patients were asked to complete a self-reported questionnaire regarding their physical activity, medical history, and the core lower urinary tract symptom score (CLSS) questionnaire, with anonymity. The association between each urinary disturbance category and the clinical characteristics of the patients such as age, gender, physical activity, and underlying disease was evaluated. RESULTS: In total, 51 patients (33 men and 18 women; mean age, 71.7 years) were eligible for analysis. The average time after the first stroke onset was 8.5 years. Nocturia and urgency incontinence had the greatest impact on the quality of life. Overactive bladder symptoms such as nocturia, urgency, urgency incontinence, and stress urinary incontinence were associated with age, female sex, and having a co-existing medical condition (such as ischemic heart disease, hypertension, and depression). Voiding symptoms such as slow stream and straining were associated with age and physical activity after stroke. CONCLUSIONS: Storage symptom is associated with not only neurological deficits but also sex and the presence of general diseases, whereas voiding symptom is influenced by physical activity in patients with chronic stroke. Therefore, lower urinary tract symptoms should be carefully monitored and physical rehabilitation should also be considered in patients with stroke.

Effects of Duloxetine on Urethral Continence Reflex and Bladder Activity in Rats with Cerebral Infarction.

PURPOSE: We investigated the effect of duloxetine, a norepinephrine and serotonin reuptake inhibitor, on the sneeze induced continence reflex and on bladder function in rats with cerebral infarction. MATERIALS AND METHODS: Using urethane anesthesia the effect of duloxetine (1 mg/kg intravenously) on the amplitude of urethral responses during sneezing as well as urethral baseline pressure at the mid urethra was evaluated in normal female adult rats and cerebral infarction rats. Tilt leak point pressure was also measured. In normal and cerebral infarction rats continuous cystometry was evaluated before and after duloxetine injection. RESULTS: In cerebral infarction rats urethral baseline pressure was 43% lower than in normal rats but the amplitude of urethral responses during sneezing did not differ in the 2 groups. Duloxetine increased the amplitude of urethral responses during sneezing and urethral baseline pressure by 31% and 21%, respectively, in normal rats but did not affect either in cerebral infarction rats. Also, in cerebral infarction rats leak point pressure was 29% lower compared with normal rats. Duloxetine increased leak point pressure in normal rats but not in cerebral infarction rats. Cerebral infarction reduced intercontraction intervals without affecting the amplitude of bladder contractions compared with normal rats. Duloxetine prolonged intercontraction intervals in cerebral infarction rats but not in normal rats. CONCLUSIONS: These results suggest that cerebral infarction induces not only bladder overactivity but also stress urinary incontinence, which may account for mixed incontinence in patients with cerebral infarction. After cerebral infarction duloxetine reduced bladder overactivity but failed to enhance active urethral closure mechanisms during sneezing, suggesting that disorganization of the brain network after cerebral infarction might influence the effect of duloxetine on lower urinary tract function.

Awareness of folic acid use increases its consumption, and reduces the risk of spina bifida.

The majority of neural tube defects were believed to be folic acid (FA)-preventable in the 1990s. The Japanese government recommended women planning pregnancy to take FA supplements of 400 µg/d in 2000, but the incidence of spina bifida has not decreased. We aimed to evaluate the OR of having an infant with spina bifida for women who periconceptionally took FA supplements and the association between an increase in supplement use and possible promoters for the increase. This is a case-control study which used 360 case women who gave birth to newborns afflicted with spina bifida, and 2333 control women who gave birth to healthy newborns during the first 12 years of this century. They were divided into two 6-year periods; from 2001 to 2006 and from 2007 to 2012. Logistic regression analyses were conducted to compute OR between cases and controls. The adjusted OR of having an infant with spina bifida for supplement users was 0.48 in the first period, and 0.53 in the second period. The proportion of women who periconceptionally consumed supplements significantly increased from 10 % in the first period to 30 % in the second period. Awareness of the preventive role of FA was a promoter for an increase in supplement use, and thus an FA campaign in high school seems rational and effective. The failure of the current public health policy is responsible for an epidemic of spina bifida. Mandatory food fortification with FA is urgent and long overdue in Japan.

Roles of the spinal glutamatergic pathway activated through α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors and its interactions with spinal noradrenergic and serotonergic pathways in the rat urethral continence mechanisms.

AIMS: To investigate the role of the glutamatergic pathway and its relationship to noradrenergic and serotonergic pathways in modulation of the urethral continence reflex during sneezing in rats. METHODS: In female Sprague-Dawley rats under urethane anesthesia, the effects of an α-amino-3-hydroxy-5-meth-ylisoxazole-4-propionic acid (AMPA) glutamate receptor antagonist, a norepinephrine reuptake inhibitor and a serotonin [5-hydeoxytripitamine (5-HT)]2B/2C agonist on the amplitude of urethral responses during sneezing (AURS), urethral baseline pressure (UBP), and sneeze-induced leak point pressure (S-LPP) were investigated. RESULTS: Intrathecal application (i.t.) of NBQX disodium salt (an AMPA receptor antagonist) decreased AURS dose-dependently by approximately 60% without affecting UBP and caused stress urinary incontinence (SUI) during sneezing in 60% of normal rats. Nisoxetine (i.t.), a norepinephrine reuptake inhibitor, and mCPP (i.t.), a 5-HT(2B/2C), agonist increased AURS, and NBQX (i.t.) abolished these excitatory effects of nisoxetine (i.t.) and mCPP (i.t.), whereas nisoxetine (i.t.) and mCPP (i.t.) did not enhance AURS in the presence of NBQX (i.t.). CONCLUSION: These results indicate that the glutamatergic pathway acting through AMPA receptors plays a crucial role on the active urethral closure reflex during sneezing at the spinal level, and noradrenergic and serotonergic pathways modulate the reflex via the spinal glutamatergic system in rats.

Central nervous targets for the treatment of bladder dysfunction.

BACKGROUND: The functions of the lower urinary tract, to store and periodically release urine, are dependent on the activity of smooth and striated muscles in the urinary bladder, urethra, and external urethral sphincter. This activity is in turn controlled by neural circuits in the brain, spinal cord, and peripheral ganglia. AIMS: This paper will review recent advances in our understanding of the pathophysiology of voiding disorders, especially focusing on the central nervous system. METHODS: Various neurotransmitters, including acetylcholine, norepinephrine, dopamine, serotonin, excitatory and inhibitory amino acids, adenosine triphosphate, nitric oxide, and neuropeptides, have been implicated in the neural regulation of the lower urinary tract. RESULTS: Injuries or diseases of the nervous system, as well as drugs and disorders of the peripheral organs, can produce voiding dysfunctions such as urinary frequency, urgency, or incontinence. CONCLUSION: We discuss the potential targets in the central nervous system and new modalities for the treatment of voiding dysfunction.

Inhibitory role of the spinal cholinergic system in the control of urethral continence reflex during sneezing in rats.

AIMS: The urethral continence reflex during stress conditions such as sneezing or coughing is an important mechanism preventing stress urinary incontinence (SUI). Although the spinal noradrenergic and serotonergic pathways are known to modulate this reflex activity, the role of spinal cholinergic pathways in the control of urethral continence reflex has not been elucidated. We therefore investigated the effect of intrathecal administration of an acetylcholine esterase (AChE) inhibitor, which increases ACh in synaptic terminals, and anti-cholinergic agents on the sneeze-induced urethral reflex in rats. METHODS: Female SD rats were anesthetized with urethane. Urethral function was evaluated during sneezing induced by insertion of the rat whisker into the nostril. Effects of an AChE inhibitor, neostigmine, and muscarinic or nicotinic receptor antagonists administered at the level of L6-S1 spinal cord were examined. RESULTS: Neostigmine dose-dependently and significantly decreased the amplitude of urethral responses during sneezing (A-URS) with an approximately 70% reduction at 3 nmol, without changing urethral baseline pressure. The neostigmine-induced decrease in A-URS was significantly reversed by pretreatment with atropine (nonselective muscarinic receptor antagonist), methoctramine (M2 receptor antagonist) or 4-DAMP (M3 receptor antagonist), but not with pirenzepine (M1 receptor antagonist), tropicamide (M4 receptor antagonist), or mecamylamine (nicotinic receptor antagonist). CONCLUSIONS: These results indicate that an increase in endogenous ACh in the lumbosacral spinal cord inhibits the sneeze-induced urethral continence reflex via activation of M2 and/or M3-muscarinic receptors, implying the inhibitory role of spinal cholinergic pathways in the control of urethral continence reflex under stress conditions such as sneezing.

Effects of phosphodiesterase type 5 inhibitor, tadalafil, on continence reflex in rats.

INTRODUCTION AND HYPOTHESIS: Effects of tadalafil, a phosphodiesterase type 5 inhibitor, on the urethral continence reflex induced by sneezing were investigated. METHODS: The amplitude of urethral pressure responses during sneezing (A-URS) and urethral baseline pressure (UBP) were measured in female rats using a microtransducer-tipped catheter. Sneeze leak-point pressure (S-LPP), defined as the lowest amount of pressure required to induce fluid leakage from the urethral orifice during sneezing, was measured in rats with stress urinary incontinence (SUI) induced by vaginal distension. Values were determined before and after tadalafil administration. RESULTS: Tadalafil dose dependently and significantly decreased A-URS and S-LPP. At the highest dose tested (6.0 mg/kg), A-URS and S-LPP decreased from 49.7 to 32.3 and from 63.9 to 44.2 cmH2O, respectively, whereas UBP did not significantly change. CONCLUSIONS: Tadalafil attenuated the sneeze-induced urethral continence reflex by relaxing the striated muscles of the external urethral sphincter.

[Perirenal malignant perivascular epithelioid cell tumor originating from right retroperitoneum: a case report].

A 51-year-old woman was admitted to our hospital for detailed examinations and medical treatment against the right retroperitoneum tumor and liver lesions. Computed tomography showed a 20 cm diameter enhanced mass in the right perirenal space and multiple liver metastases. Pathological examination by needle biopsy revealed a perivascular epithelioid cell tumor (PEComa). With weekly administration of a mTOR inhibitor, Temsirolimus, the tumor was reduced by about 20% one month later. The maximal response was stable disease due to RECIST v 1. 1. However, shortly after the minimal response, the disease showed progression. She died about five months after the start of molecular targeted therapy. In regard to the origin of PEComa, our report is the fifth in Japan as a case of retroperitoneal origin to the best of our knowledge.

Effects of low-intensity extracorporeal shock wave therapy on lipopolysaccharide cystitis in a rat model of interstitial cystitis/bladder pain syndrome.

PURPOSE: To investigate the effect of low-intensity extracorporeal shock wave therapy (LiESWT) on lipopolysaccharide (LPS)-induced cystitis in an animal model of interstitial cystitis/bladder pain syndrome (IC/BPS). METHODS: Sprague-Dawley rats were divided into three groups: control, cystitis (LPS group, intravesical injection of LPS (1 mg) twice), and cystitis with LiESWT (LiESWT group). On the third and fourth days, LiESWT was administered (0.12 mJ/mm2, 300 shots each time) on the lower abdomen toward the bladder. On the seventh day, the rats underwent pain assessment and a metabolic cage study. Subsequently, a continuous cystometrogram (CMG) was performed under urethane anaesthesia. Immunohistochemical studies were also performed, including S-100 staining, an immunohistochemical marker of Schwann cells in the bladder. RESULTS: In the LPS group, the pain threshold in the lower abdomen was significantly lower than that in the control group. In the metabolic cage study, the mean voided volume in the LPS group significantly increased. The CMG also revealed a significant decrease in bladder contraction amplitude, compatible with detrusor underactivity in the LPS group. Immunohistochemical studies showed inflammatory changes in the submucosa, increased fibrosis, and decreased S-100 stain-positive areas in the muscle layer of the LPS group. In the LiESWT group, tactile allodynia and bladder function were ameliorated, and S-100 stain-positive areas were increased. CONCLUSION: By restoring nerve damage, LiESWT improved lower abdominal pain sensitivity and bladder function in an LPS-induced cystitis rat model. This study suggests that LiESWT may be a new therapeutic modality for IC/BPS.

Effects of low-intensity extracorporeal shock wave on bladder and urethral dysfunction in spinal cord injured rats.

PURPOSE: To investigate the effects of low-intensity extracorporeal shock wave therapy (LiESWT) on bladder and urethral dysfunction with detrusor overactivity and detrusor sphincter dyssynergia (DSD) resulting from spinal cord injury (SCI). METHODS: At 3 weeks after Th9 spinal cord transection, LiESWT was performed on the bladder and urethra of adult female Sprague Dawley rats with 300 shots of 2 Hz and an energy flux density of 0.12 mJ/mm2, repeated four times every 3 days, totaling 1200 shots. Six weeks postoperatively, a single cystometrogram (CMG) and an external urethral sphincter electromyogram (EUS-EMG) were simultaneously recorded in awake animals, followed by histological evaluation. RESULTS: Voiding efficiency significantly improved in the LiESWT group (71.2%) compared to that in the control group (51.8%). The reduced EUS activity ratio during voiding (duration of reduced EUS activity during voiding/EUS contraction duration with voiding + duration of reduced EUS activity during voiding) was significantly higher in the LiESWT group (66.9%) compared to the control group (46.3%). Immunohistochemical examination revealed that fibrosis in the urethral muscle layer was reduced, and S-100 stained-positive area, a Schwann cell marker, was significantly increased in the urethra of the LiESWT group. CONCLUSION: LiESWT targeting the urethra after SCI can restore the EUS-EMG tonic activity during voiding, thereby partially ameliorating DSD. Therefore, LiESWT is a promising approach for treating bladder and urethral dysfunction following SCI.

Gut microbiota-based prediction for the transition from normal glucose tolerance (NGT) to impaired glucose tolerance (IGT) in a remote island cohort study.

AIM: The present cohort study explored whether specific gut microbiota (GM) profile would predict the development of impaired glucose tolerance (IGT) in individuals with normal glucose tolerance (NGT). METHODS: A total of 114 study subjects with NGT in Kumejima island, Japan participated in the present study and underwent 75 g oral glucose tolerance tests at baseline and one year later. We compared the profile of GM at baseline between individuals who consistently maintained NGT (NRN, n = 108) and those who transitioned from NGT to IGT (NTI, n = 6). RESULTS: Within-individual bacterial richness and evenness as well as inter-individual bacterial composition showed no significant differences between NRN and NTI. Of note, however, partial least squares discriminant analyses revealed distinct compositions of GM between groups, with no overlap in their 95 % confidence interval ellipses. Multi-factor analyses at the genus level demonstrated that the proportions of CF231, Corynebacterium, Succinivibrio, and Geobacillus were significantly elevated in NTI compared to NRN (p < 0.005, FDR < 0.1, respectively) after adjusting for age, sex, HbA1c level, and BMI. CONCLUSIONS: Our data suggest that increased proportion of specific GM is linked to the future deterioration of glucose tolerance, thereby serving as a promising predictive marker for type 2 diabetes mellitus.