Masafumi Kita

Relationship between overactive bladder and irritable bowel syndrome: a large‐scale internet survey in Japan using the overactive bladder symptom score and Rome III criteria

There is known to be an association between overactive bladder (OAB) and irritable bowel syndrome (IBS). The study investigates the association between OAB and IBS using an internet‐based survey in Japan. It is the first to investigate the prevalence and severity of OAB in the general population using the OAB symptom score questionnaire.

Effects of bladder outlet obstruction on properties of Ca2+ activated K+ channels in rat bladder

In this study, we investigated the effects of bladder outlet obstruction (BOO) on the expression and function of large conductance (BK) and small conductance (SK) Ca(2+)-activated K(+) channels in detrusor smooth muscle. The bladder from adult female Sprague-Dawley rats with 6-wk BOO were used. The mRNA expression of the BK channel alpha-subunit, beta1-, beta2-, and beta4-subunits and SK1, SK2, and SK3 channels were investigated using real-time RT-PCR. All subunits except for the BK-beta2, SK2, and SK3 channels were predominantly expressed in the detrusor smooth muscle rather than in the mucosa. The mRNA expression of the BK channel alpha-subunit was not significantly changed in obstructed bladders. However, the expression of the BK channel beta1-subunit and the SK3 channel was remarkably increased in obstructed bladders. On the other hand, the expression of the BK channel beta4-subunit was decreased as the severity of BOO-induced bladder overactivity progressed. In detrusor smooth muscle strips from obstructed bladders, blockade of BK channels by iberiotoxin (IbTx) or charybdotoxin (CTx) and blockade of SK channels by apamin increased the amplitude of spontaneous contractions. These blockers also increased the contractility and affinity of these strips for carbachol during cumulative applications. The facilitatory effects elicited by these K(+) channel blockers were larger in the strips from obstructed bladders compared with control bladders. These results suggest that long-term exposure to BOO for 6 wk enhances the function of both BK and SK types of Ca(2+)-activated K(+) channels in the detrusor smooth muscle to induce an inhibition of bladder contractility, which might be a compensatory mechanism to reduce BOO-induced bladder overactivity.

Association of overactive bladder and stress urinary incontinence in rats with pudendal nerve ligation injury

Approximately one-third of patients with stress urinary incontinence (SUI) also suffer from urgency incontinence, which is one of the major symptoms of overactive bladder (OAB) syndrome. Pudendal nerve injury has been recognized as a possible cause for both SUI and OAB. Therefore, we investigated the effects of pudendal nerve ligation (PNL) on bladder function and urinary continence in female Sprague-Dawley rats. Conscious cystometry with or without capsaicin pretreatment (125 mg/kg sc), leak point pressures (LPPs), contractile responses of bladder muscle strips to carbachol or phenylephrine, and levels of nerve growth factor (NGF) protein and mRNA in the bladder were compared in sham and PNL rats 4 wk after the injury. Urinary frequency detected by a reduction in intercontraction intervals and voided volume was observed in PNL rats compared with sham rats, but it was not seen in PNL rats with capsaicin pretreatment that desensitizes C-fiber-afferent pathways. LPPs in PNL rats were significantly decreased compared with sham rats. The contractile responses of detrusor muscle strips to phenylephrine, but not to carbachol, were significantly increased in PNL rats. The levels of NGF protein and mRNA in the bladder of PNL rats were significantly increased compared with sham rats. These results suggest that pudendal nerve neuropathy induced by PNL may be one of the potential risk factors for OAB, as well as SUI. Somato-visceral cross sensitization between somatic (pudendal) and visceral (bladder) sensory pathways that increases NGF expression and alpha(1)-adrenoceptor-mediated contractility in the bladder may be involved in this pathophysiological mechanism.

Analysis of bladder vascular resistance before and after prostatic surgery in patients with lower urinary tract symptoms suggestive of benign prostatic obstruction

To evaluate bladder vascular resistance before and after transurethral resection of the prostate (TURP).

Association of ED with chronic periodontal disease

To examine the relationship between chronic periodontal disease (CPD) and ED, the interview sheet including the CPD self-checklist (CPD score) and the five-item version of the International Index of Erectile Function (IIEF-5) was distributed to 300 adult men who received a comprehensive dental examination. Statistical analyses were performed by the Spearmans rank correlation coefficient and other methods. Statistical significance was accepted at the level of P<0.05. The interview sheets were collected from 88 men (response rate 29.3%, 50.9±16.6 years old). There was a statistically significant correlation between the CPD score and the presence of ED (P=0.0415). The results in the present study suggest that ED is related to the damage caused by endothelial dysfunction and the systematic inflammatory changes associated with CPD. The present study also suggests that dental health is important as a preventive medicine for ED.

Effect of Imidafenacin on Nocturia and Sleep Disorder in Patients with Overactive Bladder

Objective: To evaluate the efficacy of imidafenacin on nocturia and sleep disorder in patients with overactive bladder (OAB). Patients and Methods: A prospective multicenter study of imidafenacin 0.1 mg twice daily for patients with OAB and nocturia was conducted. At baseline and at week 4 and 8, patients were assessed using the overactive bladder symptom score (OABSS), frequency volume charts (FVC) and the Pittsburgh Sleep Quality Index (PSQI). Results: Treatment with imidafenacin significantly improved OAB symptoms. Imidafenacin also improved PSQI, especially subjective sleep quality, sleep latency and daytime dysfunction. In FVC, the number of daytime voids and nighttime voids significantly decreased and average voided volume significantly increased after imidafenacin. Subanalysis of FVC based on the patients’ age revealed that nocturnal polyuria was more often found in patients aged 75 years or over than in those aged under 75 years (79 vs. 55%, p < 0.05). Treatment with imidafenacin significantly reduced the nocturnal polyuria index only in patients aged 75 years or over. Conclusions: Imidafenacin can improve nocturia and sleep disorder in patients with OAB. The efficacy of imidafenacin on nocturia is attributable to an increase in bladder capacity and a decrease in nocturnal urine volume. We conclude that imidafenacin is an effective and safe drug for nocturia in patients with OAB.

ROLE OF M2 AND M3 MUSCARINIC ACETYLCHOLINE RECEPTOR SUBTYPES IN ACTIVATION OF BLADDER AFFERENT PATHWAYS IN SPINAL CORD INJURED RATS

OBJECTIVE To evaluate the role of M2 and M3 muscarinic acetylcholine receptor (mAChR) subtypes in the activation of bladder afferent pathways in rats with chronic spinal cord injury (SCI). METHODS Adult female Sprague-Dawley rats were spinalized at the T9 level. Continuous cystometry was performed under awake conditions 2 or 4 weeks after SCI. The effects of intravesical administration of an mAChR agonist (oxotremorine-methiodide), a nonselective antagonist (atropine), an M2-selective antagonist (methoctramine), and an M3-selective antagonist (darifenacin) were examined. After cystometry, the bladder was removed and separated into the mucosa and detrusor, and the M2 and M3 mAChR mRNA expression in the mucosa was determined using real-time quantitative polymerase chain reaction. RESULTS At 2 and 4 weeks after SCI, intravesical administration of a nonselective mAChR agonist (25 μM oxotremorine-methiodide) increased the area under the curve of nonvoiding contractions, although the intercontraction interval of voiding contractions and maximal voiding pressure did not change. This effect was blocked by atropine and methoctramine (10 μM) but not by darifenacin (50 μM). However, mAChR antagonists alone (10-50 μM) had no effect on cystometric parameters. M2 mAChR mRNA expression was increased in the mucosa of SCI rats compared with that in normal rats. CONCLUSION Our results suggest that the M2 mAChR subtype plays an important role in bladder afferent activation that enhances detrusor overactivity in SCI rats. However, because mAChR antagonists alone did not affect any cystometric parameters, the muscarinic mechanism controlling bladder afferent activity might not be involved in the emergence of detrusor overactivity in SCI.

Micturition-suppressing region in the periaqueductal gray of the mesencephalon of the cat

The periaqueductal gray (PAG) of the mesencephalon has been implicated to be involved in the control of micturition. We investigated the micturition-suppressing region in the PAG of the cat. Decerebrated 27 adult cats were used. A microelectrode was inserted stereotaxically into the PAG, and a region was searched where electrical stimulation suppressed isovolumetric bladder contractions. Simultaneous stimulation of the pontine micturition center (PMC) and micturition-suppressing region in the PAG was performed before and after an injection of bicuculline (GABA(A) blocker) into the PMC. The micturition-suppressing region was found at the dorsolateral margin of the rostral PAG. Bladder contractions were not provoked by simultaneous stimulation of the PMC and micturition-suppressing region in the PAG. However, after bicuculline injection into the PMC, partial bladder contractions were provoked by simultaneous stimulation of the PMC and the micturition-suppressing region in the PAG. These results suggest that the dorsolateral margin of the rostral PAG includes the micturition-suppressing region that seems to have neural connections with the PMC. GABA is assumed to be one of the neurotransmitters that are involved in the PMC inhibition from the micturition-suppressing region in the PAG.

Urodynamic effects of dutasteride add‐on therapy to alpha‐adrenergic antagonist for patients with benign prostatic enlargement: Prospective pressure‐flow study

We prospectively investigated the effect of dutasteride on clinical and urodynamic parameters in patients with benign prostatic enlargement (BPE).

Effect of intrathecal administration of E‐series prostaglandin 1 receptor antagonist in a cyclophosphamide‐induced cystitis rat model

Objectives:  To investigate the effect of intrathecal administration of E‐series prostaglandin 1 antagonist in cyclophosphamide‐induced murine cystitis.