Alpha1 -adrenergic receptors mediate bladder overactivity induced by cold stress in rats with bladder outlet obstruction.

PURPOSE: To determine if alpha1 -adrenergic receptors (AR) mediate bladder overactivity induced by cold stress in rats with bladder outlet obstruction (BOO). MATERIALS AND METHODS: The urethras of 10-week-old female Sprague-Dawley rats were ligated to create BOO. After 4 weeks, cystometric investigations were performed at room temperature (RT, 27 ± 2°C) for 20 min. The rats were then given 0.3 mg/kg naftopidil (n = 6) or vehicle (n = 5) intravenously. Five minutes later, they were transferred to low temperature (LT, 4 ± 2°C), and the cystometric patterns were again recorded for 40 min. In BOO rats and in sham-operated rats (n = 8) the expression levels of alpha1A - and alpha1D -AR mRNAs and the presence of alpha1A - and alpha1D -AR immunoreactivity on calcitonin gene-related peptide (CGRP)-positive nerve cells were investigated. RESULTS: During LT exposure, the vehicle-treated BOO rats exhibited cold stress-induced bladder overactivity. In the naftopidil-treated rats, the increase of basal pressure and decreases of both voiding interval and bladder capacity induced by LT were significantly reduced compared to the vehicle-treated animals. In the bladders of BOO rats exposed to LT, the expression of alpha1D -AR mRNA was significantly higher than in sham-operated rats, and the immunoreactivity for alpha1D -ARs on the CGRP-positive nerve cells tended to be more pronounced. CONCLUSIONS: Alpha1 -ARs mediate part of the bladder overactivity induced by cold stress in rats with BOO. Cold stress increases the expression of alpha1D -AR mRNA and the immunoreactivity for alpha1D -ARs on the CGRP-positive nerve cells in BOO rats. Naftopidil partially inhibits the cold stress overactivity, suggesting that it is mediated, at least partially, through alpha1D/1A -ARs.

[UNDIFFERENTIATED CARCINOMA OF THE URETER WITH FETAL CLINICAL COURSE: A CASE REPORT].

Undifferentiated carcinoma of ureter is rare neoplastic lesion, and the natural history of undifferentiated carcinoma of ureter has not been known well yet. We hereby presented an autopsy case of undifferentiated carcinoma of the ureter with rapid progression from the initial stage. A 62-year-old male visited the local urologist complaining of asymptomatic gross hematuria. Cystoscopy revealed the outflow of hematuria from the right ureteral orifice. Abdominal CT showed the right hydronephrosis with atrophic change of the renal parenchyma and the stenosis of upper ureter. He was referred to our hospital on suspicion of a right ureteral tumor. Magnetic resonance imaging and retrograde ureterography did not reveal a tumor in the right ureter. He complained of low back pain 4 months after the initial hematuria, and CT revealed the diffuse enlargement of the right kidney, swelling of the abdominal lymph nodes, and lung nodules. Renal biopsy was done, and only undifferentiated cells were revealed histopathologically without any specific findings to diagnose the primary organ. The tumor increased progressively, and he died about 6 months after the initial gross hematuria. Autopsy was performed, and urothelial carcinoma was found in the right ureter as the primary lesion. The ureteral tumor infiltrated to the right kidney, right adrenal gland, liver, duodenum, and pancreas with undifferentiation. Undifferentiated tumor cells were also found in distant metastatic lesion including the abdominal lymph nodes, left adrenal gland, liver, lung, pleura, and peritoneum.

[A case of advanced prostate fibrosarcoma that reacted well to chemotherapy].

Prostate fibrosarcoma is an extremely rare tumor for which complete excision has been the mainstay of treatment. Although chemotherapy has been attempted in cases with positive surgical margins and/or advanced stage disease, the effectiveness of this therapy has not been established. Herein, we report a case of advanced prostate fibrosarcoma that reacted well to chemotherapy. A 40-year-old man was referred for treatment of a large prostatic tumor with multiple lung, liver, and bone metastases. Needle biopsy of the prostate revealed that the tumor was a high-grade undifferentiated sarcoma. Chemotherapy with doxorubicin and ifosfamide was administered. After five courses of chemotherapy, the primary prostate tumor decreased markedly, and the lung and liver metastases almost disappeared. Radical cystoprostatectomy and ileal conduit formation were performed. Pathological diagnosis was fibrosarcoma. Another three courses of doxorubicin and ifosfamide therapy were performed, and doxorubicin was replaced by etoposide because the maximum dose of doxorubicin was reached. However, the effectiveness of the second-line therapy was poor, and the tumor progressed again. The patient died of lung metastasis 15 months later.

The relationship between α1-adrenergic receptors and TRPM8 channels in detrusor overactivity induced by cold stress in ovariectomized rats.

PURPOSE: We studied whether cold stress induced detrusor overactivity in ovariectomized rats is associated with increased thermosensitive TRPM8 channel expression in the skin and whether the response could be inhibited by α1-adrenergic receptor blockade. MATERIALS AND METHODS: A total of 24 Sprague-Dawley® rats at postnatal week 30 were randomly selected for ovariectomy (16) or sham ovariectomy (8). Five weeks later cystometric measurements of conscious, freely moving rats were made at room temperature (mean ± SEM 28C ± 2C) for 20 minutes. Eight ovariectomized rats were intravenously administered 1.0 mg/kg naftopidil. The other 8 ovariectomized and 8 sham operated rats were given naftopidil-free vehicle. Five minutes later they were transferred to a low temperature environment (mean 4C ± 2C) and micturition patterns were again recorded. TRPM8 channel expression in lumbar skin was estimated by real-time reverse-transcriptase polymerase chain reaction and immunohistochemistry. RESULTS: TRPM8 channel mRNA and protein in the skin of ovariectomized rats were significantly higher than in sham operated rats. At room temperature micturition parameters were similar in sham operated and ovariectomized rats. At low temperature sham operated and ovariectomized rats showed cold stress induced detrusor overactivity but increased micturition frequency and decreased bladder capacity were significantly greater in ovariectomized rats. Treatment of ovariectomized rats with naftopidil inhibited cold stress induced detrusor overactivity. CONCLUSIONS: Cold stress induced detrusor overactivity in rats with decreased estrogen is associated with TRPM8 channel up-regulation in the skin and mediated by nerve pathways using α1-adrenergic receptors.

A galenical produced from Ba-Wei-Die-Huang-Wan (THC-002) provides resistance to the cold stress-induced detrusor overactivity in conscious rats.

AIMS: We determined if THC-002, a galenical produced from Ba-Wei-Die-Huang-Wan, could increase skin temperature and inhibit detrusor overactivity induced by sudden whole body cooling. Further, we determined if THC-002 could decrease expression of transient receptor potential melastatin 8 (TRPM8) channels associated with the cold responses. METHODS: Hind leg skin temperature of female 10-week-old Sprague-Dawley rats was measured by thermal imaging. Experimental rats (n = 12) were given oral 100 mg/kg THC-002 daily for one week, and controls (n = 12) were similarly treated with THC-002-free solution. Afterwards, thermal imaging and cystometric investigations of the freely moving conscious rats were performed at room temperature (RT, 27 ± 2°C) for 20 min. The rats were then transferred to a low temperature (LT, 4 ± 2°C) environment during which thermal imaging and cystometric measurements were taken at 5, 10, 20, 30, and 40 min. Afterward, the skin tissues were harvested to estimate expression levels of TRPM8 channels by immunohistochemistry and real-time reverse-transcription polymerase chain reaction. RESULTS: The RT skin temperature of THC-002-treated rats was significantly higher than controls. During the first 20 min under LT, the control rats exhibited cold stress-induced detrusor overactivity such as decreased voiding interval and bladder capacity. THC-002 partially inhibited the detrusor overactivity patterns. During the second 20 min, skin temperature was relatively stable, and the detrusor overactivity of both groups slowly disappeared. THC-002 significantly reduced expression of TRPM8 channel protein and mRNA. CONCLUSIONS: THC-002 inhibited cold stress-induced detrusor overactivity resulting from decreasing skin temperature. Therefore, THC-002 might provide resistance to cold stress-exacerbated lower urinary tract symptoms.

Relationship between expression of ß3-adrenoceptor mRNA in bladder mucosa and urodynamic findings in men with lower urinary tract symptoms.

AIMS: To investigate the relationship between urinary bladder mucosal expression of ß3-adrenoceptor (AR) mRNA and urodynamic findings in patients with lower urinary tract symptoms and benign prostatic obstruction (BPO). METHODS: During surgical prostate resection of 32 BPO patients, mucosal biopsies were collected and analyzed by reverse transcriptase polymerase chain reaction to determine the expression level of ß3-AR mRNA. First desire to void (FDV) and strong desire to void (SDV), detrusor overactivity (DO), and bladder outlet obstruction (BOO) were measured pre-operatively. Patients with FDVs < 200 ml or SDVs < 300 ml were assigned to the small capacity group (n = 19). Patients with FDVs > 201 ml and SDVs > 301 ml were assigned to the large capacity group (n = 13). The same patients with positive DO were also assigned to the DO+ group (n = 11), and those with negative DO were assigned to the DO- group (n = 21). Finally, patients whose position on the Schäfer nomogram was greater than degree V were assigned to the severe BOO group (n = 17), while those with less than degree IV were assigned to the mild BOO group (n = 15). RESULTS: The expression level of ß3-AR mRNA was similar in both bladder capacity groups and both DO groups. However, the expression level in the severe BOO group was significantly less than in the mild BOO group (P = 0.043). CONCLUSIONS: The expression of bladder mucosal ß3-AR mRNA was significantly decreased in patients with severe BOO, suggesting that ß3-ARs might be affected by the degree of BOO.

Functional roles of transient receptor potential melastatin 8 (TRPM8) channels in the cold stress-induced detrusor overactivity pathways in conscious rats.

AIMS: We determined if transient receptor potential melastatin 8 (TRPM8) channels are involved in the detrusor overactivity induced by menthol, or exposure to low temperature (LT). METHODS: Two days prior to cystometric investigation, the bladders of 10-week-old Sprague-Dawley rats were cannulated to measure bladder pressure. After a 20 min baseline cystometry period, the TRPM8 channel antagonist, N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)piperazine-1-carboxamide (BCTC), or vehicle, was administered through a jugular vein catheter (n = 6). A 90% menthol solution was sprayed onto bare leg skin once every 5 min for 20 min, and then cystometric measurements were repeated. After a 30-min recovery period, the rats were intravenously administered 0.1 µmol/kg BCTC. Five minutes later, they were again sprayed and cystometry recorded. In separate experiments, cannulated rats were intravenously administered 0.001, 0.01, or 0.1 µmol/kg BCTC (n = 6 each dose). Five minutes later, they were exposed to LT (4 ± 2°C) for 20 min of cystometry. RESULTS: Menthol spray decreased voiding interval, micturition volume, and bladder capacity in the BCTC-free rats. However after BCTC administration, these effects were prevented. Exposure to LT elicited detrusor overactivity that caused decreased voiding interval, micturition volume, and bladder capacity. However, at 0.01 and 0.1 µmol/kg, BCTC inhibited this cold stress-induced detrusor overactivity. CONCLUSIONS: Since the TRPM8 channel agonist, BCTC, inhibited detrusor overactivity in rats sprayed with the TRPM8 channel agonist, menthol, and the drug also inhibited cold stress-induced detrusor overactivity, we conclude that TRPM8 channels mediate, at least partially, detrusor overactivity elicited by exposure to LT.

Male lower urinary tract symptoms and α1D-adrenoceptors.

Historically, α(1)-adrenoceptors have been classified into three subtypes (α(1)(A), α(1)(B) and α(1)(D)) that are widely distributed in various organs. Research on the α(1)(D)-adrenoceptors in the bladder, urethra and prostate has focused on the relationship between expression levels and symptoms of bladder outlet obstruction, and the implications and functional roles of α(1)(D)-adrenoceptors subtypes in these organs. The α(1)(D)-adrenoceptor messenger ribonucleic acid and protein seem to be increased in obstructed bladders or small capacity bladders. In contrast, α(1)(D)-adrenoceptor subtype knock-out mice have been found to have a prolonged voiding interval. Interestingly, an α(1)(D)-adrenoceptor antagonist was found to inhibit the facilitation of afferent nerve activity for the micturition reflex induced by intravesical infusion of acetic acid. Clinically, patients who felt urgency at low filling volumes and had a small bladder capacity were found to have more α(1)(D)-adrenoceptor messenger ribonucleic acid in their bladder mucosa than patients who felt urgency at high filling volumes and had a large bladder capacity. An α(1)(D)-adrenoceptor antagonist was found to increase the first desired volume and the maximum desired volume while decreasing detrusor overactivity in pressure flow studies. Thus, α(1)(D)-adrenoceptors in the lower urinary tract might play an important role in the pathophysiology of lower urinary tract disorders.

A galenical of traditional Chinese herbal mixture (THC-002) reduces expression of tachykinin peptides within urethras of spontaneously hypertensive rats.

AIMS: We investigated expression of tachykinin peptides neurokinin A, neurokinin B, and substance P within urethras of spontaneously hypertensive rats (SHRs) and determined if a traditional Chinese herbal mixture, THC-002, decreased them. METHODS: Ten- and 40-week-old male SHRs were randomly separated into three groups (n = 12 each). Rats of one group were given orally 20 ml 0.9% NaCl solution per kg body weight daily for 1 week. One hour later, each received a similar volume of water. Rats in the second group were also given saline. One hour later, each received 20 mg THC-002 per kg body weight. The third group was untreated. The urethras were removed and separated into prostatic and non-prostatic regions and analyzed by real-time reverse transcription polymerase chain reaction (n = 6) and immunohistochemistry (n = 6). RESULTS: In 40-week-old untreated SHRs, neurokinin B mRNA and protein, and substance P mRNA in prostatic urethras were significantly higher compared to the 10-week-old ones. Neurokinin A mRNA and protein, and substance P protein of the 40-week-old saline-loaded prostatic urethras were significantly higher compared to the 40-week-old untreated ones. In 40-week-old untreated SHRs, the non-prostatic urethral neurokinin B protein was significantly higher compared to the 10-week-old ones. In 40-week-old, saline-loaded SHRs, neurokinin A protein of the non-prostatic urethras was significantly higher compared to 40-week-old the untreated ones. In 40-week-old SHRs, THC-002 significantly decreased the expression of the urethral tachykinins, except for non-prostatic urethral neurokinin A mRNA. CONCLUSIONS: Aging and saline-loading increased the expression of urethral tachykinin mRNAs and peptides. THC-002 partially decreased them.

Relation between expression of α(1)-adrenoceptor mRNAs in bladder mucosa and urodynamic findings in men with lower urinary tract symptoms.

OBJECTIVE: To investigate the possible relationship between the bladder mucosal expression of α(1)-adrenoceptor (AR) mRNAs, storage symptoms and urodynamic findings in patients with lower urinary symptoms (LUTS) and benign prostatic obstruction (BPO). MATERIAL AND METHODS: Mucosa was obtained from the posterior bladder wall from 20 patients with a diagnosis of LUTS and BPO undergoing prostatectomy. α(1)-AR subtype mRNA was quantified using competitive real-time reverse transcription-polymerase chain reaction. A preoperative video urodynamic study measured volumes for first desire to void (FDV) and strong desire to void (SDV). Patients were divided into group 1, with volumes for FDV ≤ 200 ml or SDV ≤ 300 ml, and group 2, with volumes FDV ≥ 201 ml and SDV ≥ 301 ml. Preoperative and postoperative international prostate symptom score (IPSS) and Overactive Bladder Symptom Score (OABSS) were evaluated. RESULTS: The group 1 FDV (141.0 ± 13.5 ml) was significantly lower than that of group 2 (299.0 ± 48.1 ml). Similarly, the SDV for group 1 (247.0 ± 21.9 ml) was also significantly lower than for group 2 (444.0 ± 32.5 ml). There were no significant differences between groups 1 and 2 with respect to mucosal α(1a)- and α(1b)-AR mRNA levels. However, group 1 patients had significantly more α(1d)-mRNA than those in group 2. No relationship between the expression of α(1)-AR mRNAs and preoperative or postoperative OABSS or IPSS was detected. CONCLUSION: There was a relationship between the expression of α(1d)-AR mRNA in the bladder mucosa and storage-phase urodynamics in LUTS/BPO patients, suggesting a role of α(1D)-ARs in bladder sensation.

Stimulation of skin menthol receptors stimulates detrusor activity in conscious rats.

AIMS: The Transient Receptor Potential Melastatin (TRPM)8 channel, activated by menthol and cool temperatures, has been proposed to be a cool receptor involved in mediation of the bladder response in the diagnostic ice water test. We examined the expression of TRPM8 in the rat skin and investigated if stimulation of skin menthol receptors by menthol can induce detrusor activity in conscious rats. METHODS: Immunofluorescence staining for TRPM8 was performed in samples of the skin from the leg and back of the rats. Continuous cystometry was performed in conscious animals. Voiding interval (VI), micturition volume (MV), and bladder capacity (BC) were evaluated before and after spraying menthol solution to the skin of the leg and back of the rats. RESULTS: Immunohistochemical analysis revealed that TRPM8 was expressed in the investigated tissues. The expression of TRPM8-positive receptors was not significantly different between the leg and back skin. Saline caused no significant change in cystometric parameters. After spraying menthol solution (50% and 99% to the skin of the leg, and 99% to the back skin), VI, MV, and BC decreased significantly. CONCLUSIONS: TRPM8 is expressed in rat skin. Spraying menthol solution onto the skin-induced detrusor activity, an effect we suggest is mediated by stimulation of TRPM8 receptors.

An extract (THC-002) of Ba-Wei-Die-Huang-Wan inhibits expression of tachykinins, and P2X3 and TRPV1 receptors, and inhibits ATP-induced detrusor overactivity in spontaneously hypertensive rats.

AIMS: To investigate possible mechanisms of action of THC-002 (HARNCARE), a galenical produced from the traditional Chinese herbal mixture Ba-Wei-Die-Huang-Wan, which has been reported to improve lower urinary tract symptoms (LUTS) in patients. METHODS: Forty-five female SHRs were randomly separated into three groups. Two groups were given 20 ml physiological saline solution (PSS) per kg-body weight orally daily for 1 week. An hour after the administration of PSS, one of the groups received 20 mg THC-002 per kg body weight, and the other a similar volume of THC-002-free saline. The third group received no treatments. The bladders were analyzed by real time RT-PCR (n = 6) and immunohistochemistry (n = 3) for the expression of tachykinins and P2X3 and TRPV1 receptors. Cystometric investigation (n = 6) was conducted after intravesical instillation of saline followed by 5 mg/ml ATP solution. RESULTS: Treatment with PSS caused and upregulation of tachykinins and P2X3 and TRPV1 receptors, which was prevented in the group treated with THC-002. In the normal (non-treated) and non-THC-002-treated SHRs, instillation of the ATP solution decreased voiding interval, micturition volume, and bladder capacity compared to the instillation of saline. However, in the THC-002-treated SHRs, ATP instillation had no effect. CONCLUSIONS: In SHRs, THC-002 reduced the bladder expression of tachykinins and P2X3 and TRPV1 receptors, and inhibited ATP-induced detrusor overactivity. These effects may explain part of its beneficial effects on LUTS.

Expression of 5-Hydroxytryptamine Receptors in Human Urinary Bladders with Benign Prostatic Hyperplasia.

INTRODUCTION: This study investigated the mRNA expression pattern and distribution of 5-hydroxytryptamine (5-HT) receptors 5-HT2A, 5-HT2B, 5-HT3A, 5-HT4, and 5-HT7 within the urothelium and detrusor of normal bladder tissue and in the urothelium of bladders from patients with benign prostatic hyperplasia (BPH). METHODS: Normal urinary bladder specimens were obtained from 13 patients undergoing radical cystectomy due to bladder cancer (normal group) and BPH specimens were obtained from 27 benign prostatic obstruction patients receiving transurethral prostatectomy or retropubic prostatectomy. Receptor subtype mRNA expression was determined by real-time reverse transcription polymerase chain reaction on urothelium, detrusor, and whole mucosal preparations. Receptor distribution was determined by immunohistochemistry. RESULTS: In normal tissues, expressions of 5-HT2B and 5-HT7 receptor mRNAs in the urothelium, detrusor, and whole mucosa were greater than the average expression for all receptor subtype mRNAs. 5-HT2B receptor protein was distributed in the apical urothelium and among the detrusor smooth muscle layers. In contrast, the 5-HT7 receptors were within the urothelium middle cell layers and detrusor smooth muscle cells. The expression pattern of each 5-HT receptor subtype mRNA within the BPH urothelium was similar to that in the normal urothelium. The expression level of 5-HT2A receptor mRNA in the BPH group was significantly lower than the normal group; however, the expressions of both 5-HT3A and 5-HT7 mRNAs were significantly higher. The expressions of both 5-HT2B and 5-HT4 mRNAs were not significantly different between the normal and BPH groups. CONCLUSION: In normal urinary bladders, the expressions of both 5-HT2B and 5-HT7 mRNAs were higher compared to the 5-HT2A, 5-HT3A, and 5-HT4 mRNAs. The distributions of 5-HT2B and 5-HT7 receptors were different in the urothelium and detrusor layers. The 5-HT3A and 5-HT7 receptor mRNAs in the BPH group were significantly higher compared to the normal urothelium, while the 5-HT2A mRNA was significantly lower. FUNDING: Asahi Kasei Pharma Corporation.

[A case of stone formation in the Mainz pouch using appendix as the efferent limb: a case report].

A large calculus (6.0 x 4.5 x 7.0 cm sized) in the continent urinary pouch was detected incidentally by computed tomography in a 7-year-old man with a gall bladder stone. He underwent a total cystectomy and Mainz pouch formation using appendix as the efferent limb for bladder cancer 7 years ago. Urine culture showed Proteus mirabilis and Escherichia coli, and urine pH was 8.5. The stone was removed successfully through a pouchotomy and composed mainly of struvite. The stone analysis was MAP; 88% and CaCO3; 12%. Convalescence was uneventful. This is the first case of in Mainz pouch using appendix as the efferent limb.

Implantation of autologous adipose-derived cells reconstructs functional urethral sphincters in rabbit cryoinjured urethra.

We investigated the ability of autologous adipose-derived cells injected into cryoinjured rabbit urethras to improve urinary continence and explored the possible mechanisms by which it occurred. Adipose tissue was harvested from the perivesical region of nine 10-week-old female New Zealand White rabbits and cultured for 7 days. Immediately after harvesting the tissue, we injured the internal urethral orifice by spraying liquid nitrogen for 20 s. The cultured cells expressed the mesenchymal cell marker STRO1, but not muscle cell markers myoglobin or smooth muscle actin (SMA). Just before implantation, the adipose-derived cells were labeled with the PKH26 fluorescent cell linker. Autologous 2.0×10(6) adipose-derived cells (five rabbits) or a cell-free control solution (four rabbits) was injected around the cryoinjured urethras at 7 days after injury. Fourteen days later, the leak point pressure (LPP) was measured, and the urethras were harvested for immunohistochemical analyses. At 14 days after implantation, LPP of the cell-implanted group was significantly higher compared with the cell-free control group (p<0.05). In immunohistochemical examination, the reconstructed skeletal and smooth muscle areas in the cell-implanted regions were significantly more developed than those in controls (p<0.01). Implanted PKH26-labeled adipose-derived cells were immunohistochemically positive for myoglobin, SMA, and Pax7 antibodies, which are markers for skeletal muscles, smooth muscles, and myoblast progenitor cells, respectively. In addition, these implanted cells were positive for the nerve cell markers, tubulin ß3, S100, and the vascular endothelial cell marker, von Willebrand factor. Furthermore, some of the implanted cells were positive for the transforming growth factor ß1, nerve growth factor, and vascular endothelial growth factor. In conclusion, implantation of autologous adipose-derived cells into the cryoinjured rabbit urethras promoted the recovery of urethral function by myogenic differentiation, neuroregeneration, and neoangiogenesis of the implanted cells and/or the surrounding tissues as well as by bulking effects. Thus, treatment of human radical prostatectomy-related stress urinary incontinence by adipose-derived cell implantation could have significant therapeutic effects.

Correlation Between Bladder Mucosal Alpha-1D/Alpha-1A Adrenoceptor mRNA Ratio and Lower Urinary Tract Function in Benign Prostatic Obstruction Patients.

OBJECTIVES: Alpha-1 adrenoceptor (AR) antagonists are commonly used as therapeutic agents for patients with benign prostatic obstruction (BPO). Our objective was to investigate the correlation between the ratio of bladder mucosal alpha-1D/alpha-1A adrenoceptor mRNA and lower urinary tract function in BPO patients. METHODS: In 20 BPO patients, the expression level of alpha-1 AR mRNAs in the bladder mucosal biopsies was investigated by reverse transcriptase polymerase chain reaction. The subjects were divided into two groups. In Group 1, the ratio of alpha-1D mRNA to alpha-1A mRNA was greater than one. In Group 2, the ratio was less than one. We determined the correlation by Schäfer nomogram between Group 1 and Group 2 patients and lower urinary tract function as determined by a video urodynamic study. RESULTS: Two patients were excluded due to inability to void. Another was excluded because the alpha-1D/alpha-1A mRNA ratio was one. On the Schäfer nomogram, six of nine Group 1 cases had obstructions less than IV and normal or weak detrusor contractility. For Group 2, six of eight cases had obstructions more than IV and normal or strong detrusor contractility. CONCLUSION: Patients with higher levels of alpha-1D AR mRNA were distinct from those with higher alpha-1A AR mRNA levels with regard to obstruction and detrusor activity. The results suggest that the Schäfer nomogram might be useful in determining which alpha-1 AR antagonists are better for BPO patients suffering from storage symptoms.

Relationship between Toe Temperature and Lower Urinary Tract Symptoms.

OBJECTIVE: Cold stress can elicit increases in urinary urgency and frequency. We determined if there was a relationship between finger and toe temperatures and lower urinary tract symptoms (LUTS). METHODS: We studied 50 people who visited a public health management seminar. The participants were divided into two groups according to self-described sensitivity to cold stress. The cold non-sensitive (CNS) group consisted of 3 males and 20 females (66.9 ± 10.8 years old), and the cold sensitive (CS) group consisted of 4 males and 23 females (65.8 ± 8.01 years old). Each participant was assessed to determine international prostate symptom score (IPSS), overactive bladder symptom score (OABSS), and quality of life (QOL) score. They were then instructed on lifestyle changes and exercises that could improve peripheral blood flow and provide relief for their LUTS. Next, the temperatures of their middle fingers and toes were measured before and after 5-10 min of the exercises. Two weeks later, the IPSS, OABSS, and QOL scores were reassessed. RESULTS: Before exercise, the middle fingers were significantly warmer than the middle toes. Exercise had no significant effect on the middle finger temperature of either group; however, it did increase the middle toe temperature for both groups. The increase was greatest for the CS group. The CS group had higher LUTS storage symptoms than the CNS group, and these improved after 2 weeks of lifestyle changes and exercise. CONCLUSION: Improvements in lifestyle and daily exercise may be effective for LUTS in CS people.

Implantation of autologous bone-marrow-derived cells reconstructs functional urethral sphincters in rabbits.

The purpose of this study was to determine if implantation of autologous bone-marrow-derived cells has the potential to treat stress urinary incontinence caused by intrinsic sphincter deficiency. Bone marrow cells harvested from femurs of New Zealand White rabbits were cultured for 10 days. Seven days before implantation, the urethral sphincters located at the internal urethral orifice were cryo-injured by spraying liquid nitrogen for 15 s. The cultured autologous bone-marrow-derived cells were implanted 7 days after cryo-injury. For controls, cell-free solutions were injected. At 7 and 14 days after implantation, leak point pressures were determined and the urethral sphincters were examined by immunohistochemistry. At 7 and 14 days, the cell-implanted regions contained numerous striated and smooth muscle-like cells expressing myoglobin and smooth muscle actin, respectively. The proportions of myoglobin- and smooth muscle actin-expressing areas in both the 7- and 14-day cell-implanted regions were significantly higher than in controls. By 14 days, these differentiated cells formed contacts with similar cells, creating layered muscle structures. At that time, the leak point pressure of the cell-implanted rabbits was significantly higher than that of the controls. In conclusion, autologous bone-marrow-derived cells can reconstruct functional urethral sphincters.

Analysis of the Pressure-Flow Study in Weak Detrusor Patients with Benign Prostatic Hypertrophy.

OBJECTIVE: Pressure-flow study is a method used to evaluate the degree of bladder outlet obstruction and the strength of detrusor contractility during voiding. However, whether or not the operation for benign prostate hyperplasia should be avoided in detrusor underactivity patients remains controversial. To address this, we performed a retrospective analysis of our pressure-flow study data for benign prostate hyperplasia patients. We especially focused on the backgrounds of patients with weak detrusor contractility. METHODS: Patients (n = 288; average age, 71.5 years) who underwent pressure-flow study to evaluate operative indications between February 2001 and April 2010 were included in this study. We analyzed the relationships between background factors and detrusor contraction strength according to Schäfer's nomogram. RESULTS: Patients with weak detrusor contractility had poor flow (5.81 mL/sec) and low voided volume (141.2 mL) compared to patients with normal (8.77 mL/sec, 202.0 mL) or strong (8.97 mL/sec, 178.3 mL) detrusor contractility. Twenty-six of 74 weak detrusor patients underwent prostate operation. The operated group had high obstruction grade (3.35, P < 0.001), but a low rate of detrusor overactivity (19.2%, P < 0.05), compared to the non-operated group (2.16, 41.7%). The operated group also had high urinary retention rate (38.5%) compared to the non-operation group (18.8%). CONCLUSION: We performed prostate surgery in patients who had episodes of urinary retention, with outlet obstruction, and with no detrusor overactivity, even in those with weak detrusor contractility. The operation may not be contraindicated for these patients. Pressure-flow study is an important tool to ensure adequate informed consent.