Gene expression profiles during tissue remodeling following bladder outlet obstruction.

Bladder outlet obstruction (BOO) often results in lower urinary tract symptoms (LUTSs) and negatively affects quality of life. Here, we evaluated gene expression patterns in the urinary bladder during tissue remodeling due to BOO. We divided BOO model rats into two groups according to the degree of hypertrophy of smooth muscle in the bladder. The strong muscular hypertrophy group, which exhibited markedly increased bladder smooth muscle proportion and HIF1α mRNA levels compared with the control group, was considered a model for the termination of hypertrophy, whereas the mild muscular hypertrophy group was considered a model of the initiation of hypertrophy. Some genes related to urinary function showed different expression patterns between the two groups. Furthermore, we found that several genes, including D-box binding PAR bZIP transcription factor (DBP), were upregulated only in the mild muscular hypertrophy group. DBP expression levels were increased in bladder smooth muscle cells in response to hypoxic stress. DBP associated with enhancer and promoter regions of NOS3 gene locus and upregulated NOS3 gene expression under hypoxic conditions. These findings suggested that the regulatory systems of gene expression were altered during tissue remodeling following BOO. Furthermore, circadian clock components might be involved in control of urinary function via transcriptional gene regulation in response to hypoxic stimuli.

Association of serum carotenoid levels with urinary albumin excretion in a general Japanese population: the Yakumo study.

BACKGROUND: Albuminuria is a risk factor for not only nephropathy progression but also cardiovascular disease. Oxidative stress may have a role in the positive association between albuminuria and cardiovascular disease. METHODS: This cross-sectional study investigated the associations of serum levels of carotenoids, which are dietary antioxidants, with albuminuria among 501 Japanese adults (198 men, mean age ± SD: 66.4 ± 10.0 years; 303 women, mean age ± SD: 65.4 ± 9.8 years) who attended a health examination. Serum levels of carotenoids were determined by high-performance liquid chromatography. Logistic regression analysis was used to estimate odds ratios (ORs) with 95% CIs for albuminuria after adjustment for age, body mass index, smoking habits, drinking habits, hypertension, diabetes mellitus, and dyslipidemia. RESULTS: Prevalence of albuminuria was 15.4% among men and 18.1% among women. Among women with albuminuria, geometric mean serum levels of canthaxanthin, lycopene, ß-carotene, total carotenes, and provitamin A were significantly lower than those of normoalbuminuric women. Adjusted ORs for albuminuria among women in the highest tertiles of serum ß-carotene (OR, 0.45; 95% CI, 0.20-0.98) and provitamin A (OR, 0.45; 95% CI, 0.20-0.97) were significantly lower as compared with those for women in the lowest tertile. There were no associations between serum carotenoids and albuminuria in men. CONCLUSIONS: An increased level of serum provitamin A, especially serum ß-carotene, was independently associated with lower risk of albuminuria among Japanese women.

Urge perception index of bladder hypersensitivity.

PURPOSE: By analyzing bladder diaries with patient self-reported urinary perception grades, we developed the urge perception index, a quantitative measure of bladder hypersensitivity. We evaluated the impact of the urge perception index on the definition of overactive bladder severity. MATERIALS AND METHODS: We retrospectively evaluated the records of 69 female patients who visited our outpatient clinic with the complaint of storage symptoms. Patients were asked to complete the overactive bladder symptom score and a 3-day bladder diary with self-reported grading of urinary perception on a range of 1 to 5 per void. Overactive bladder was diagnosed in 43 patients and nonoveractive bladder was diagnosed in 26. The urge perception index was defined as voided volume divided by the urinary perception grade at each void. RESULTS: We analyzed 1,578 reported voids. According to the urinary perception grade, urge perception index values for overactive bladder were significantly lower than those for nonoveractive bladder (grades 1 to 4 p <0.001). The average ± SD urge perception index in 3-day bladder diaries was lower in overactive than in nonoveractive bladder cases (55 ± 28 vs 133 ± 73, p <0.0001). The most severe (lowest) single urge perception index value during the 3 days was significantly lower in patients with overactive than with nonoveractive bladder (mean 20 ± 12 vs 62 ± 40, p <0.0001). There were negative linear correlations of the urge perception index with total overactive bladder symptom scores (r = -0.598, p <0.0001) and with an urgency symptom score (r = -0.557, p <0.0001). CONCLUSIONS: The urge perception index, an integrated parameter of patient reported bladder perception and voided volume, could be promising to quantify the severity of overactive bladder or bladder hypersensitivity by bladder diary analysis.

Analysis of nocturia with 24-h urine volume, nocturnal urine volume, nocturnal bladder capacity and length of sleep duration: concept for effective treatment modality.

OBJECTIVE: • To determine the relationship between the number of nocturia and 24-h urine volume, nocturnal urine volume, nocturnal bladder capacity and length of sleep duration as well as to assess the significance of these factors with respect to eliminating nocturnal voidings in individual patients with nocturia. PATIENTS AND METHODS: • Among 532 participants who completed a 3-day bladder diary between April 2005 and December 2006, the diaries of 450 participants without 24-h polyuria were analyzed. • Clinical variables such as the number of daytime and night-time voids, 24-h urine volume, nocturnal polyuria index, daytime and night-time maximum voided volumes (MVV), night/day MVV ratio, sleep duration and proportion of night/day urine production rates were obtained from each diary. • Participants were classified into eight groups according to values of three factors: nocturnal MVV, proportion of night/day urine production rates and length of sleep duration. • Each group was divided into three subgroups: non-nocturics (number of nocturnal voidings is zero), mild nocturics (number of nocturnal voidings is one) and severe nocturics (number of nocturnal voidings is two or more). • The data from non-nocturics with three normal factors were regarded as the normal control and compared with the variables of the other subgroups using Dunnett's method. RESULTS: • Variables that form the basis of classifying participants into eight groups and corresponding to abnormal factors of each group were statistically significant in all the subgroups of each group. • Furthermore, a significantly increased 24-h urine volume was found in severe nocturics of the group with three normal factors. • A significantly decreased 24-h urine volume was found in non-nocturics of groups with nocturnal polyuria, decreased bladder capacity and both long sleep duration and nocturnal polyuria. • A significantly increased nocturnal MVV and night/day MVV ratio were shown in non-nocturics and mild nocturics of the groups with nocturnal polyuria and both long sleep duration and nocturnal polyuria. CONCLUSIONS: • Because nocturia is a multifactorial disorder and closely related to four factors (i.e. 24-h urine volume, nocturnal urine volume, nocturnal bladder capacity and length of sleep duration), the evaluation of all these factors appears to be clinically useful for determining the main contributing factor in patients with nocturia as well as the suitable treatment modality on an individual basis. • Physicians should take all these factors into consideration in the evaluation and treatment of nocturia.

Impact of convenience void in a bladder diary with urinary perception grade to assess overactive bladder symptoms: a community-based study.

AIM: Bladder diaries including bladder perception grade were analyzed to assess convenience void (CV) in community-dwelling women 40 years of age or older. METHODS: A total of 310 women completed a 3-day bladder diary with a grade for bladder perception. The grade was defined on scores 0-5 as follows: 0 = No bladder sensation, 1 = Sensation of bladder filling without desire to void, 2 = Desire to void, 3 = Strong desire to void, 4 = Urgency without urge urinary incontinence (UUI), and 5 = Urge incontinence episode. CV was defined as void without desire to void: when the grade was 0, CV in a narrow sense, and when 0 or 1, CV in a broad sense. RESULTS: The incidence of CV in the broad sense significantly decreased with age. Of the 310 women, 48 (15.5%) had overactive bladder (OAB) symptoms on the medical interview, including 37 (11.9%) without UUI (OAB-Dry) and 11 (3.5%) with UUI (OAB-Wet). Of the remaining 262 women, 111 (35.8%), who had urgency but a urinary frequency of 7 or less, and another 141 (48.7%) were classified into the Normal with Urgency and Normal without Urgency groups, respectively. The incidence of CV in a broad sense in the Normal without Urgency group was significantly greater than that in the Normal with Urgency and OAB-Wet groups. The mean voided volumes of CV in the broad sense in the OAB-Wet group were significantly smaller than those in the other three groups. CONCLUSIONS: The evaluation of CV may be a new tool in assessing storage condition and voiding dysfunction.

The effects of sacral acupuncture on acetic acid-induced bladder irritation in conscious rats.

OBJECTIVES: To investigate the effects of sacral acupuncture on acetic acid-induced bladder irritation using cystometry in conscious rats, with particular focus on effects on afferent fibers of the bladder. METHODS: A total of 40 female Sprague-Dawley rats weighing 200-270 g were used. The animals were divided into 5 groups: (1) rats with bladder overactivity induced by acetic acid, without sacral acupuncture stimulation (irritated bladder group); (2) rats treated with sacral acupuncture stimulation after induction of bladder overactivity by acetic acid (acupuncture stimulation group); (3) rats treated with sacral acupuncture stimulation after capsaicin desensitization (capsaicin-desensitized group); (4) rats treated with atropine (atropine injection group); and (5) rats treated with sacral acupuncture stimulation after nonacetic acid infusion (nonirritated bladder group). Cystometry was carried out without anesthesia, and the following variables were measured in all animals: intercontraction interval (ICI), basal pressure, threshold pressure, and micturition pressure. RESULTS: In the acupuncture stimulation group, sacral acupuncture stimulation resulted in a 140.1 +/- 5.9% increase in ICI after acetic acid-induced irritation to an interval similar to baseline (P = .072). A significant difference in the percent of ICI increase was observed between the acupuncture stimulation and irritated bladder groups (P < .01). In the capsaicin-desensitized groups and acupuncture stimulation groups, no significant differences in ICI occurred, before and after acupuncture. CONCLUSIONS: Sacral acupuncture could contribute to improve acetic acid-induced bladder irritation through inhibition of capsaicin-sensitive C-fiber activation.

Analysis of bladder diary with urinary perception to assess overactive bladder symptoms in community-dwelling women.

AIM: Bladder diaries including bladder perception grades were analyzed to assess overactive bladder (OAB) symptoms in community-dwelling women 40 years of age or older. METHODS: Three hundred ten women (mean 58 years) completed a 3-day bladder diary. The perception grades were defined as follows: 0 = no bladder sensation, 1 = sensation of bladder filling without desire to void, 2 = desire to void, 3 = strong desire to void, 4 = urgency without urge urinary incontinence (UUI), and 5 = urgency with UUI. RESULTS: Forty-eight women (15.5%) had OAB symptoms on medical interview, including 37 (11.9%) without UUI (OAB-Dry) and 11 (3.5%) with UUI (OAB-Wet). In the analysis of 5,709 voids, the voided volume significantly increased with the grades of perception. The 24 hr voided volume in the OAB-Dry group was significantly larger than that in the Normal group. The average voided volume in the OAB-Wet group was significantly smaller than in the OAB-Dry and the Normal groups. The mean voided volume at grade 3 in the Normal without urgency group was significantly larger than volumes in any other group. In the analysis of grades 4 and 5, voided volumes in the OAB-Wet group were significantly smaller than those in the Normal and/or OAB-Dry groups. CONCLUSIONS: A bladder diary that includes a new bladder perception grade was thought to be useful in assessing urinary sensation or incontinence as well as voiding pattern. The causes of symptoms such as urgency or urinary frequency may be different between the Normal, OAB-Dry, and OAB-Wet groups.

Sleep duration is an independent factor in nocturia: analysis of bladder diaries.

OBJECTIVE To analyse the relationship between the number of nocturia episodes and other variables obtained from a bladder diary, with special attention to the duration of sleep, as nocturia is closely related to sleep disorders. PATIENTS, SUBJECTS AND METHODS Between April 2005 and December 2006, 532 participants, including both community-dwelling subjects who underwent a mass screening programme and outpatients who consulted the department of urology, completed a 3-day bladder diary. Clinical variables, i.e. the number of daytime and night-time voids, diurnal and nocturnal urine volume, daytime and night-time maximum voided volume, sleep duration and nocturnal polyuria index (NPi) were obtained from the diary. The variables were assessed by univariate analysis in all participants, and by multiple regression analysis of all participants, males, females, subjects in mass screening and those with no 24-h polyuria, to determine which variables were independently associated with the number of nocturia episodes. RESULTS Univariate analysis showed a considerable correlation between the nocturia episodes and age, nocturnal urine volume, NPi and sleep duration. On multiple regression analysis, age, nocturnal urine volume, night-time maximum voided volume and sleep duration were independently related to number of nocturia episodes in all subgroups. CONCLUSIONS Sleep duration was confirmed as an independent factor in nocturia. Sleep conditions, including sleep duration, should be considered when evaluating and treating patients with nocturia.

Effects of acupuncture for chronic pelvic pain syndrome with intrapelvic venous congestion: preliminary results.

BACKGROUND: The present study was designed to reveal the usefulness of acupuncture for chronic pelvic pain syndrome with intrapelvic venous congestion as evaluated by symptom scores, transrectal ultrasonography (TRUS) and magnetic resonance (MR) venography. METHODS: Ten male patients suffering from non-inflammatory chronic pelvic pain syndrome (NIH category IIIB) with intrapelvic venous congestion were treated using acupuncture. Eight patients had previously received pharmacotherapy, which was unsuccessful. Acupuncture was performed using disposable stainless steel needles, which were inserted into the bilateral BL-33 points and rotated manually for 10 min. The treatment was repeated every week for 5 weeks without other therapeutic maneuvers. Results from TRUS and MR venography, as well as clinical symptoms based on the NIH chronic prostatitis symptom index (NIH-CPSI) and the international prostate symptom score (IPSS), were compared before and after the treatment. RESULTS: No side-effects were recognized throughout the treatment period. The average pain and QOL scores of the NIH-CPSI 1 week after the 5th acupuncture treatment decreased significantly (P < 0.05 and P < 0.01, respectively) compared with the baseline. The maximum width of the sonolucent zone 1 week after the 5th treatment also decreased significantly (P < 0.01, compared with the baseline). Intrapelvic venous congestion demonstrated by MR venography was significantly improved in four patients. CONCLUSION: This study provided novel information concerning the therapeutic effects of acupuncture on non-inflammatory chronic pelvic pain syndrome.

Possible contribution of prostatic anterior fibromuscular stroma to age-related urinary disturbance in reference to pressure-flow study.

Recently, we reported that the anterior fibromuscular stroma (AFMS) of the prostate has significant different innervation compared with the other glandular regions of the prostate. In healthy volunteers (n = 12) using transrectal ultrasound (US), or TRUS, monitoring during voiding, we observed dynamic change (p < 0.0001) of the thickness of the AFMS during voiding. The aim of this study was to reveal the possible functional contribution of the AFMS to micturition, as well as the age-related voiding dysfunction. In the patients (n = 56) with voiding dysfunction who underwent both pressure-flow study (PFS) for determining obstruction and TRUS monitoring during voiding, we measured the ultrasonic dynamic change of the lower urinary tract during voiding. In old men with voiding dysfunction, ultrasonic measurements of dynamic change in the AFMS (p < 0.01) as well as the opening urethra (p < 0.05) could contribute to diagnosing of the anatomical localization of obstructive lesions. The poor movement of AFMS could account for the age-related urinary disturbance in the patients without benign prostatic enlargement and without bladder neck obstruction.

Neuroselective current perception threshold evaluation of bladder mucosal sensory function.

OBJECTIVE: To evaluate human bladder mucosal sensory function by neuroselective Current Perception Threshold (CPT) measures from healthy and neuropathic bladders. METHODS: Eight healthy volunteers and 38 patients with urinary symptoms underwent conventional urodynamic tests including water-filling cystometry and ice water test. Standardized neuroselective CPT measures were obtained from the left index finger and the mucosa of the posterior bladder wall. Three different CPTs were obtained from each test site using a constant alternating current sinusoid waveform electrical stimulus presented at 2000Hz, 250Hz and 5Hz stimulation frequencies, which could selectively reflect the functions of the large myelinated fibers (A-beta-fiber), the small myelinated fibers (A-delta-fiber), and the unmyelinated fibers (C-fiber), respectively. RESULTS: As the determination of CPT values on the finger skin, the CPT values in the bladder could be determined using the neuroselective measures in all patients but three who had no sensory response (absence of sensation) caused by complete spinal injury. In the 8 patients with detrusor hyperreflexia due to incomplete spinal cord injury (supra-sacral lesion), the bladder CPT value (4.0+/-1.9) at 5Hz was significantly lower (p<0.01) than that in the controls (26.2+/-17.7). In the neurogenic bladders determined to be underactive (n=11, including post pelvic surgery, post infra-sacral level spinal cord injury and diabetes patients), the higher CPT values of bladder mucosal sensory functions were found at 5Hz (p<0.05), 250Hz (p=0.07), and 2000Hz (p<0.05) compared to the controls. CONCLUSIONS: Quantitative neuroselective measurement of CPT values in the human bladder mucosal function was feasible. Hypersensitivity or hyposensitivity of the urinary sensory function could be determined using the CPT values in comparison to control. The quantitative neuroselective estimation of the bladder sensory functions in different types of sensory peripheral nerve fibers may contribute to the appropriate selection of therapeutic strategy in patients with urinary sensory dysfunction.

Treatment of monosymptomatic nocturnal enuresis by acupuncture: A preliminary study.

OBJECTIVES: This study was designed to clarify the clinical usefulness of acupuncture as a treatment option for monosymptomatic nocturnal enuresis, and evaluate the mechanisms of its effect. METHODS: Subjects comprised 15 patients (10 males, 5 females) with monosymptomatic nocturnal enuresis who were treated by acupuncture using a disposable stainless steel needle (0.3 mm in diameter, 60 mm in length) inserted into bilateral BL-33 (Zhongliao) points on the skin of the third posterior sacral foramina and rotated manually for 10 min reciprocally. Bladder capacities and number of wet nights per week were compared before and after treatment. Patients in whom wet nights decreased 50% or more compared with the baseline were considered responders. RESULTS: Nocturnal enuresis improvement rates following acupuncture treatment were 40% (6/15) just after treatment and 47% (7/15) 2 months after. In 6 responders, just after treatment the nocturnal bladder capacity (NBC) increased significantly, from 201 mL to 334 mL (P < 0.05). No side-effects were recognized throughout the treatment period. CONCLUSION: Acupuncture may be beneficial in the treatment of nocturnal enuresis by increasing NBC, and provide a promising alternative to conventional therapies for monosymptomatic nocturnal enuresis.