Biomedical subjects

Teruhiko Yokoyama

Publications and source records attributed to Teruhiko Yokoyama.

At least 19 recordsLinked to original sources

PubMed2006

Comparison of 25 and 75 mg/day naftopidil for lower urinary tract symptoms associated with benign prostatic hyperplasia: a prospective, randomized controlled study.

BACKGROUND: The present study investigated the efficacy, safety, and utility of starting an alpha(1d)-selective antagonist, naftopidil, at 75 or 25 mg/day in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). METHODS: In this prospective comparative study, the subjects comprised 153 patients with LUTS associated with BPH. Patients were randomized to receive either 25 mg/day (Group LD) or 75 mg/day (Group HD) of naftopidil for 4 weeks. The lower urinary tract disease symptom score (LUTDSS), the International Prostate Symptom Score (IPSS), the Quality of life assessment index, the maximum flow rate (Q(max)), and the residual urine volume were compared between the groups. RESULTS: In both groups, the LUTDSS and the IPSS were significantly improved at the endpoint and no significant intergroup differences were identified. However, the improvement in the Q(max) was significantly better for Group HD than for Group LD. The overall efficacy did not differ significantly between the groups. The degree of improvement in voiding symptoms and LUTDSS among patients with moderate symptoms was significantly greater for Group HD than for Group LD. The frequency of adverse reactions did not differ significantly between the groups. CONCLUSIONS: Starting administration at 75 mg/day rather than 25mg/day is helpful for LUTS associated with BPH for patients with moderate symptoms, particularly in improving voiding symptoms. The 75 mg/day administration was considered to be a recommendable therapeutic dose in some patients.

Adrenergic alpha-Antagonists↗

PubMed2006

Involvement of STAT3 in bladder smooth muscle hypertrophy following bladder outlet obstruction.

We examined the involvement of the signal transducer and activator of transcription 3 (STAT3) in bladder outlet obstruction (BOO)-induced bladder smooth muscle hypertrophy using a rat in vivo and in vitro study. BOO induced increases in bladder weight and bladder smooth muscle thickness 1 week after the operation. By using antibody microarrays, 64 of 389 proteins blotted on the array met our selection criteria of an INR value between > or = 2.0 and < or = 0.5. This result revealed up-regulation of transcription factors, cell cycle regulatory proteins, apoptosis-associated proteins and so on. On the other hand, down-regulation (INR value < or = 0.5) of proteins was not found. In a profiling study, we found an increase in the expression of STAT3. A significant increase in nuclear phosphorylated STAT3 expression was confirmed in bladder smooth muscle tissue by immunohistochemistry and Western blot analysis. Cyclical stretch-relaxation (1 Hz) at 120% elongation significantly increased the expression of STAT3 and of alpha-smooth muscle actin in primary cultured bladder smooth muscle cells. Furthermore, the blockade of STAT3 expression by the transfection of STAT3 small interfering RNA (siRNA) significantly prevented the stretch-induced increase in alpha-smooth muscle actin expression. These results suggest that STAT3 has an important role in the induction of bladder smooth muscle hypertrophy.

Animals↗

PubMed2006

Combination chemotherapy with estramustine phosphate, ifosfamide and cisplatin for hormone-refractory prostate cancer.

We evaluated the efficiency and toxicity of estramustine phosphate (ECT), ifosfamide (IFM) and cisplatin (CDDP) combination chemotherapy in twenty-one patients with hormone-refractory prostate cancer (HRPC), for which there is currently no effective treatment. Patients received a daily dose of 560 mg ECT in combination with 1.2 g/m2 IFM on days 1 to 5 and 70 mg/m2 CDDP on day 1. This combination therapy was given every 3 to 4 weeks. An objective response of more than 50% reduction in prostate-specific antigen was observed in 9 of 18 patients (50%), and a more than 50% reduction in bi-dimensionally measurable soft-tissue lesions was observed in 2 of 7 patients (29%). The median duration of response among the cases showing partial response was 40 weeks, while the median duration of response of overall partial-response plus stable cases was 30 weeks. The median survival duration of all cases was 47 weeks. Toxicity was modest and acceptable. In conclusion, the ECT, IFM and CDDP combination chemotherapy regimen is a viable treatment option for HRPC. However, in comparison with our previous chemotherapy regimen of IFM and CDDP, no additional long-lasting effects resulting from the inclusion of ECT could be affirmed.

Adult↗

PubMed2005

p53 protein transduction therapy: successful targeting and inhibition of the growth of the bladder cancer cells.

INTRODUCTION: Virus-mediated gene therapy for bladder cancer has some problems, such as efficiency of gene delivery and safety issues. We have reported that poly-arginine peptide (11R) has the ability to increase protein transduction in cells. Here, we show that p53 protein transduction using 11R is useful for targeting to bladder tumors and suppressing the growth of bladder cancer cells. MATERIALS AND METHODS: An 11R-fused p53 protein (11R-p53) was transduced in bladder cancer cell lines (J82 and T24) to evaluate the anti-tumor effect. Cell viability was assessed by performing the 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST) assay. To investigate whether 11R-p53 enhanced the effect on anti-cancer drug-dependent apoptosis of bladder cancer cells, the cell lines were cotreated with 11R-p53 and cis-diaminedichloroplatinum (CDDP). Apoptotic cells were identified using Hoechst staining. To investigate the efficiency of protein transduction mediated by 11R in bladder tumors in vivo, SCID mice were transplanted with J82 cells in the bladder and 11R-GFP was transurethrally transduced into the bladder. The transduction of 11R-GFP in the tumor was examined by confocal microscopy. RESULTS: 11R-p53 inhibited the growth of both J82 and T24 cells in a dose-dependent manner. The transduction of 11R-p53 enhanced CDDP-dependent induction of apoptosis. Transurethral application of 11R-GFP resulted in transduction of GFP in bladder tumors but not in the normal bladder epithelium or subepithelial tissues. CONCLUSION: The present results suggest that p53 protein transduction therapy may be a promising method for the treatment of bladder cancer.

Genetic Therapy↗

PubMed2005

Accuracy of two noninvasive methods of diagnosing bladder outlet obstruction using ultrasonography: intravesical prostatic protrusion and velocity-flow video urodynamics.

OBJECTIVES: We assessed the accuracy of two noninvasive, ultrasound methods of diagnosing bladder outlet obstruction (BOO). The potential for the combined methods to enhance the accuracy of diagnosis was also assessed. METHODS: We evaluated 30 male outpatients using two recently developed diagnostic methods, transabdominal ultrasound grading of intravesical prostatic protrusion (IPP) and Doppler ultrasound urodynamics (Doppler UDS), as well as conventional pressure flow studies according to the research protocol. IPP has been reported to be a useful anatomic parameter for the assessment of BOO. Doppler UDS uses transperineal ultrasonography to measure the velocity flow of urine at the prostatic and sphincteric urethras. We recruited 168 outpatients; however, of the 57 patients who fulfilled all the research criteria, only 30 were able to undergo conventional pressure flow study analysis. The results of all three diagnostic methods were analyzed statistically for reliability and relationship in the 30 patients with a BOO index from the conventional pressure flow study. RESULTS: IPP grading correlated well with the BOO index (Spearman's rho 0.624), as did the Doppler UDS parameter (Spearman's rho 0.736). The combination of IPP grading and Doppler UDS showed good sensitivity and specificity. CONCLUSIONS: We confirmed the accuracy of the two novel methods. The combination of the two methods may be a novel standard in the diagnosis of BOO in male patients.

Aged↗

PubMed2005

Tolerability and morbidity of urodynamic testing: a questionnaire-based study.

OBJECTIVES: To determine the tolerability and morbidity rate of multichannel urodynamics (UDS). METHODS: A total of 154 consecutive patients were included in the present study; 87 men and 67 women underwent UDS and completed a questionnaire. All patients undergoing UDS were given a two-part questionnaire. The first part, given immediately after UDS, contained four questions regarding pain, embarrassment, and physical burden (assessed with a visual analogue scale on which 0 = not at all, 10 = unbearable), as well as willingness to undergo UDS again. The second part, given within 2 weeks after UDS, contained five questions regarding micturition pain, gross hematuria, dysuria, cloudy urine, and fever episodes after UDS. Urine specimens were also analyzed. RESULTS: The mean (+/-SD) degrees of pain, embarrassment, and physical burden were 2.27 +/- 2.53, 2.59 +/- 2.69, and 1.76 +/- 2.43, respectively, and 73.6% of men and 80.6% of women were willing to repeat UDS. The most common complaint after UDS was micturition pain. Two men and 1 woman had fever after UDS; there was no relationship between fever and urinary tract infections. Urinalysis showed that 4.6% of men and 7.5% of women had leukocyturia after the investigation. CONCLUSIONS: The complication rates of UDS were relatively low. For most patients, UDS were tolerable and acceptable. Proper informed consent is necessary.

Adult↗

PubMed2005

Preliminary results of the effect of extracorporeal magnetic stimulation on urinary incontinence after radical prostatectomy: a pilot study.

INTRODUCTION: Radical prostatectomy is a common procedure for the treatment of clinically localized prostate cancer. However, urinary incontinence is a significant potential source of morbidity following surgery. Extracorporeal magnetic stimulation (ExMS) is a new technology used for pelvic muscle strengthening in the treatment of stress urinary incontinence. We investigated the clinical effects of ExMS on urinary incontinence after retropubic radical prostatectomy. PATIENTS AND METHODS: Ten patients who had suffered from urinary incontinence for more than 12 months following radical prostatectomy were enrolled in this study. The Neocontrol system was used. Treatment sessions were for 20 min, twice a week for 2 months. The frequency of the pulse field was 10 Hz for 10 min, followed by a second treatment at 50 Hz for 10 min. Objective and subjective measures included voiding diaries, 1-hour pad weight testing, and a quality of life survey at 1, 2, 3, and 6 months after starting the treatment. Urodynamic studies were performed before and after treatment. RESULTS: Three patients became dry (30%), 3 patients improved (30%), and 4 patients showed stationary symptoms (40%). In the 1-hour pad weight testing, the mean pad weight decreased from 25 to 10.3 g, and the quality of life scores had improved from 70.5 to 84.9 2 months after treatment. The frequency of leak episodes per day was reduced from 5.0 times before to 1.9 times after treatment. In the urodynamic study, mean maximum cystometric capacity and Valsalva leak point pressure increased from 197 +/- 53.2 to 309 +/- 85.3 ml and from 67.3 +/- 22.6 to 97.1 +/- 22.7 cm H2O after treatment, respectively (p < 0.05). 3 of 6 patients who showed improvement returned to the baseline values within 12 months after treatment and requested maintenance ExMS therapy. No side effects were observed. CONCLUSIONS: ExMS therapy offered a new option for urinary incontinence treatment after radical prostatectomy. Further studies are required to determine how long the benefits of treatment last and whether maintenance therapy is necessary.

Aged↗

PubMed2005

Long-term clinical outcomes of 420 consecutive prostate cancer patients in a single institute.

This study was undertaken to reveal the trends of prostate cancer and the outcome of treatment modalities for each disease stage in patients in a single institute over a 10-year period. From January 1994 through December 2003, 420 consecutive patients with previously untreated and histologically confirmed prostate cancer were analyzed for annual distributions of disease stages and treatment modalities and for long-term clinical progression-free survival, prostate cancer-specific survival, and prostate-specific antigen (PSA) failure-free survival rates for each stage and treatment modality. Annual trends showed that the number of patients, especially those with clinically localized cancer, increased dramatically. The 5-year disease-specific survival rates for patients with clinically localized disease were 100 percent for all treatment modalities, including hormonal therapy alone. Patients with PSA levels less than 10 ng/ml showed an 81 percent 5-year PSA failure-free survival rate with radical prostatectomy. Stage C patients treated by surgery or radiation-based therapy with concomitant hormonal therapy obtained 93 percent and 100 percent cause-specific survival rates, respectively, and those treated by hormonal therapy alone showed a 79 percent rate. The number of patients with localized prostate cancer was increasing in this decade. While long-term hormonal therapy alone was highly efficient in controlling localized prostate cancer, radical therapies in conjunction with neo-adjuvant hormonal therapy produced better survival rates in cases of locally advanced disease.

Academies and Institutes↗

PubMed2004

Comparative study of effects of extracorporeal magnetic innervation versus electrical stimulation for urinary incontinence after radical prostatectomy.

OBJECTIVES: To perform a randomized comparative study to investigate the clinical effects of extracorporeal magnetic innervation (ExMI) and functional electrical stimulation (FES) on urinary incontinence after retropubic radical prostatectomy. METHODS: Thirty-six patients with urinary incontinence after radical prostatectomy were randomly assigned to three groups (12 patients each in the FES, ExMI, and control groups). For FES, an anal electrode was used. Pulses of 20-Hz square waves at a 300-micros pulse duration were used for 15 minutes twice daily for 1 month. For ExMI, the Neocontrol system was used. The treatment sessions were for 20 minutes, twice a week for 2 months. The frequency of the pulse field was 10 Hz for 10 minutes, followed by a second treatment at 50 Hz for 10 minutes. For the control group, only pelvic floor muscle exercises were performed. Objective measures included bladder diaries, 24-hour pad weight testing, and a quality-of-life survey, at 1, 2, and 4 weeks and 2, 3, 4, 5, and 6 months after removing the catheter. RESULTS: The leakage weight during the 24 hours after removing the catheter was 684, 698, and 664 g for the FES, ExMI, and control groups, respectively. At 1 month, it was 72, 83, and 175 g (FES versus control, P <0.05) and at 2 months was 54, 18, and 92 g (ExMI versus control, P <0.05) in the FES, ExMI, and control groups, respectively. Finally, 6 months later, the average 24-hour leakage weight was less than 10 g in all groups. Quality-of-life measures decreased after surgery, but gradually improved over time in all groups. No complications were noted in any of the groups. CONCLUSIONS: ExMI and FES therapies offered earlier continence compared with the control group after radical prostatectomy. We consider ExMI and FES to be recommendable options for patients who want quick improvement of postoperative urinary incontinence.

Aged↗

PubMed2004

Role of C afferent fibers and monitoring of intravesical resiniferatoxin therapy for patients with idiopathic detrusor overactivity.

PURPOSE: Resiniferatoxin (RTX) is a specific C fiber neurotoxin which produces desensitization. In this study we performed intravesical RTX therapy in patients with idiopathic detrusor overactivity. In addition we measured the current perception threshold of C and A delta fibers before and after treatment to evaluate clinical significance. MATERIALS AND METHODS: The protocol involved an RTX solution (100 ml of 50 nM) instilled in the bladder for 30 minutes. Four men and 6 women 59 to 75 years old were treated. Effects on bladder function were evaluated before and 30 days after treatment by cystometry and Neurometer (Neurotron, Inc., Baltimore, Maryland). Subjective and objective measures included bladder diaries and quality of life before treatment, and 7, 30 and 90 days subsequently. RESULTS: Of the 10 patients 5 noted improvement and 2 of them became dry. The other 5 patients were considered to have stationary symptoms. Mean maximal cystometric capacity +/- SD increased from 229 +/- 108 ml at baseline to 271 +/- 99.5 ml at 30 days (p = 0.04). The mean number of daily episodes of urinary incontinence decreased from 3.5 +/- 2.2 to 2.0 +/- 1.6 (p = 0.008) at 7 days, to 1.9 +/- 1.6 (p = 0.018) at 30 days and to 2.5 +/- 1.7 (p = 0.018) at 90 days. Mean current perception threshold values of C and A delta fibers did not change significantly, from 46.9 +/- 35.2 to 56.4 +/- 32.1 (p = 0.161) and from 66.9 +/- 31.7 to 66.4 +/- 25.2 (p = 0.952), respectively. However, values of C fibers increased in all patients who showed improvement from 46.2 +/- 33.2 to 64.0 +/- 36.8 (p = 0.043). CONCLUSIONS: Intravesical RTX improved bladder capacity and leak episodes in patients with idiopathic detrusor overactivity. Intravesical RTX is a promising treatment for this condition.

Administration, Intravesical↗

PubMed2004

Intravesical resiniferatoxin for patients with neurogenic detrusor overactivity.

BACKGROUND: Resiniferatoxin (RTX), a substance isolated from some species of Euphobia, is a specific C-fiber neurotoxin which produces desensitization rather than excitation. At first, we performed intravesical RTX therapy on eight patients with neurogenic detrusor overactivity. After we confirmed the safety and efficacy, a Japanese RTX study group was organized and a new protocol made. The multicenter trial was performed in Japan. However, the efficacy of the treatments was different among the institutions. Therefore, we have compared the results between the first protocol and the new one at our hospital. METHODS: The first and second protocol involved the RTX solution (30 mL of 500 nM, and 100 mL of 1 micro M, respectively) being instillated in the bladder for 30 min by almost the same procedures. Effects on bladder function were evaluated during treatment and at follow up. RESULTS: For the first and second protocols, six out of eight patients noted symptomatic improvement while two patients did not notice any change in the degree of incontinence for one month. The mean urodynamic bladder capacity had significantly increased from 138.0 +/- 64.4 mL to 227.3 +/- 112.4 mL and 133.1 +/- 43.3 mL to 247.0 +/- 102.3 mL 1 month after RTX treatment for the first and second protocols, respectively (P < 0.05). No severe side-effects were seen in either group. CONCLUSION: Intravesical RTX improved bladder capacity in patients with neurogenic detrusor overactivity in both protocols. The concentration of RTX did not exhibit any change in the effect and safety in our hospital. Intravesical RTX is a promising treatment for neurogenic detrusor overactivity.

Administration, Intravesical↗

PubMed2004

Extracorporeal magnetic innervation treatment for urinary incontinence.

BACKGROUND: Extracorporeal magnetic innervation (ExMI) is a new technology used for pelvic muscle strengthening for the treatment of stress urinary incontinence. We explored whether this new technology is effective for patients with urge incontinence, as well as those with stress urinary incontinence. METHODS: We studied 20 patients with urge incontinence and 17 patients with stress urinary incontinence. The Neocontrol system (Neotonus Inc., Marietta, GA) was used. Treatment sessions were for 20 min, twice a week for 8 weeks. Evaluations were performed by bladder diaries, one-hour pad weight testing, quality-of-life surveys and urodynamic studies. RESULTS: Of the urge incontinence cases, five patients were cured (25.0%), 12 patients improved (60.0%) and three patients did not show any improvement (15.0%). Leak episodes per day reduced from 5.6 times to 1.9 times at 8 weeks (P < 0.05). Eight patients with urge incontinence recurred within 24 weeks after the last treatment (47.1%). Of the stress incontinence cases, nine patients were cured (52.9%), seven patients improved (41.1%) and one patient did not show any improvement (6%). In one-hour pad weight testing, the mean pad weight reduced from 7.9 g to 1.9 g at 8 weeks (P < 0.05). Three patients returned to the baseline values within 24 weeks after the last treatment (17.6%). No side-effects were experienced by any of the patients. CONCLUSION: Although the results for urge incontinence were less effective than for stress urinary incontinence, ExMI therapy offers a new option for urge incontinence as well as stress urinary incontinence.

Adult↗

PubMed2004

Change in parameters before and after alpha-1-blocker therapy for men with lower urinary tract symptoms using color doppler ultrasound urodynamics: possible application for prediction of clinical outcome.

INTRODUCTION: We previously developed a noninvasive video urodynamic study using color Doppler ultrasonography. We sought the best flow velocity-related parameter which would allow prediction of an improvement in lower urinary tract symptoms (LUTS) after alpha 1-blocker treatment. METHODS: Twenty-two men with benign prostatic hyperplasia who were treated with a nonselective alpha 1-blocker (urapidil) were included. Subjective symptoms were evaluated using the International Prostate Symptom Score (IPSS) before and after alpha 1-blocker treatment. We measured the flow velocities using a transperineal ultrasound technique in the distal prostatic urethra just proximal to the external urethral sphincter (V1) and in the sphincteric urethra (V2), and used them to obtain the velocity ratio (VR=V1/V2). The corresponding functional cross-sectional areas of the urethra at these two sites (A1 and A2) were calculated as Q(max)/V. All these parameters obtained by the velocity-flow urodynamics were compared before treatment and after 4 weeks. RESULTS: After treatment, V1 and VR were decreased, and A1 was increased. V2 correlated best with the change in IPSS before and after alpha 1-blocker therapy, with Spearman's rho of 0.584. All men with V2 exceeding 50 cm/s did not show an improvement in the LUTS. CONCLUSIONS: The maximum flow velocity at the sphincteric urethra (V2) can predict the subjective outcome of alpha 1-blocker treatment. The velocity-flow parameters changed after alpha 1-blocker treatment. We confirmed that the transperineal ultrasound urodynamic study is not only noninvasive but also informative.

Adrenergic alpha-Antagonists↗

PubMed2004

High-energy transurethral microwave thermotherapy in patients with benign prostatic hyperplasia: comparative study between 30-and 60-minute single treatments.

We retrospectively evaluated the subjective and objective treatment results of transurethral microwave thermotherapy (TUMT) for benign prostatic hyperplasia (BPH) and explored the difference in effectiveness between 30- and 60-min single treatments. From June 1997 through March 2003, 58 men with BPH underwent TUMT using the Targis device. Twenty-seven and 31 patients each received a single treatment of 60 or 30 min, respectively. Evaluations after treatment included a clinical determination of the International Prostate Symptom Score, urodynamic assessments by peak flow rate, and magnetic resonance imaging (MRI). In the 60-min treatment, the symptom score improved significantly, from 17.9 to 9.5 after 2 months. Similarly, there was a significant improvement in peak flow rate, from 6.7 to 11.2 ml/sec after 2 months. In the 30-min treatment, the symptom score also improved significantly, from 18.4 to 13.4 after 2 weeks. Similarly, there was a significant improvement in the peak flow rate, from 6.4 to 11.7 ml/sec after 1 month. MRI imaging showed necrosis of the prostate gland 2 weeks after either treatment. These results demonstrated that both the 60-min and the 30-min treatments were effective for patients with BPH. Moreover, the 30-min treatment led to quicker improvement than the 60-min treatment. Thus, a 30-min TUMT protocol is considered recommendable for this treatment.

Aged↗

PubMed2004

Effectiveness of a nonsteroidal anti-inflammatory drug for nocturia on patients with benign prostatic hyperplasia: a prospective non-randomized study of loxoprofen sodium 60 mg once daily before sleeping.

We explored the effectiveness of loxoprofen sodium (loxoprofen), which is the most common non-steroidal anti-inflammatory drug (NSAID) in Japan, for patients with benign prostatic hyperplasia (BPH) complaining of nocturia. A total of 93 BPH patients aged 49-84 years were enrolled in the study. These patients had received standard drug therapy with alpha1-blocker for BPH, followed by anticholinergic drugs, hypnotics, tricyclic antidepressants, and/or antiduretic hormone, but they still complained about 2 or more episodes of nocturia. They each took a single 60-mg tablet of loxoprofen prior to sleeping at night for 14 days in addition to their BPH treatments. The effects were assessed by questionnaire before and after treatment as excellent (nocturia disappeared or decreased by 2 or more voids/night), improved (nocturia decreased by 1 void/night), unchanged, or worsened (nocturia increased). Nocturia improved or disappeared in 74.2% of patients: excellent, improved, unchanged, and worsened results were obtained in 37.6%, 36.6%, 21.5%, and 4.3% of patients, respectively. The effects were better in patients whose baseline nocturia was > 2 times than in those with a lesser frequency at enrollment (P = 0.04). Loxoprofen can be an effective and useful treatment option for patients with BPH complaining of refractory nocturia.

Aged↗

PubMed2003

Intravesical liposome administration--a novel treatment for hyperactive bladder in the rat.

OBJECTIVES: To examine the effect of intravesical administration of liposomes (LPs) on chemically induced bladder hyperactivity in the rat. It has been suggested that interstitial cystitis (IC) is associated with a dysfunctional or leaky epithelium. Thus, enhancement of epithelial barrier function might be useful in the treatment of IC. LPs are vesicles that are concentric phospholipid bilayers separated by an aqueous compartment and can fuse with cells to provide a molecular film that can promote wound healing. METHODS: The intravesical pressure was recorded using a transurethral catheter in adult female Sprague-Dawley rats anesthetized with urethane (1.2 g/kg subcutaneously). Some animals were pretreated with capsaicin (125 mg/kg subcutaneously) 4 days before the experiments. Continuous cystometrograms were performed by slowly filling the bladder (0.04 mL/min) with solutions of varying compositions, including saline, acetic acid (AA, 0.1%), potassium chloride (KCl, 500 mM), protamine sulfate (PS, 10 mg/mL), LPs, PS/KCl, or LPs/KCl. The parameters measured included the intercontraction interval (ICI), amplitude of bladder contractions, compliance, and micturition pressure threshold. RESULTS: The ICI was decreased after exposure to AA (79.8% decrease) or PS/KCl (81% decrease); however, the ICI was not changed after LPs, PS, or KCl alone. The decreased ICI was partially reversed after infusion of LPs (172.8% increase) or LPs/KCl (63% increase), but was not significantly changed after switching to saline or KCl administration. Pretreatment with capsaicin delayed the onset of the irritative effects of AA by approximately 30 to 60 minutes, but had not changed the magnitude after 2 hours of infusion. CONCLUSIONS: Intravesical administration of PS/KCl or AA activates capsaicin-sensitive and capsaicin-resistant afferents in a time-dependent sequence that is partially reversed by LP infusion. We hypothesize that LPs might enhance the barrier properties of a dysfunctional uroepithelium and increase resistance to irritant penetration. Thus, intravesical LP administration could be a novel treatment of patients with IC.

Administration, Intravesical↗

PubMed2003

Calcineurin mediates bladder smooth muscle hypertrophy after bladder outlet obstruction.

PURPOSE: Bladder outlet obstruction (BOO) leads to compensatory bladder hypertrophy. However, the hypertrophy mechanism remains elusive. We report that calcineurin (Cn) is involved in bladder hypertrophy. MATERIALS AND METHODS: Partial BOO was surgically induced in 10-week-old female Wistar rats. The bladder was excised 2, 4 and 6 weeks following surgery in 9 rats each. Histological study was performed at each time point. Cn expression was examined by Western blot analysis. Myosin heavy chain expression was evaluated on gels stained with Coomassie blue. Primary cultured bladder smooth muscle cells were infected with recombinant adenoviruses encoding a constitutive active form of CnA (DeltaCnA), CnB and lacZ, and cell size was measured. RESULTS: In histological findings bladder smooth muscle hypertrophy was observed 2 and 4 weeks after surgery. However, the thickened muscles became thinner 6 weeks after BOO. CnA expression 2 weeks after BOO increased 3.2-fold compared with that of controls. Expression significantly decreased 4 and 6 weeks after surgery. In contrast, CnB expression was unchanged throughout hypertrophy development. Changes in myosin heavy chain expression correlated with changes in CnA. We observed significant hypertrophy in DeltaCnA and CnB over expressing smooth muscle cells. Moreover, FK506, which is a potent inhibitor of Cn, blocked hypertrophy in DeltaCnA and CnB over expressing smooth muscle cells. CONCLUSIONS: These data suggest that Cn has an important role in the induction of bladder smooth muscle hypertrophy.

Animals↗

PubMed2002

Effect of cryoinjury on the contractile parameters of bladder strips: a model of impaired detrusor contractility.

In anesthetized Sprague-Dawley rats, the bladder was exposed and cryoinjury was induced by abruptly freezing the serosal side of the bladder wall with a chilled aluminum rod previously placed on dry ice (-40 degrees C). Five days later, the rats were euthanized, and strips were prepared from the area adjacent to the injury. Neurally and alpha,beta methylene-ATP (alpha,beta m-ATP; 50 microM)-evoked contractions were measured in bladder strips from cryoinjured or intact bladders prepared from sham-operated rats. Cryoinjured bladder strips produced significantly lower contractile forces than intact strips to electrical stimulation at higher (10-40 Hz) frequencies. The maximal rate of the neurally evoked contractions was slower in the cryoinjured bladders. The contractile response to alpha,beta m-ATP was smaller in the cryoinjured preparations indicating that the changes may have also occurred at the postjunctional site. In addition, atropine was more effective at inhibiting the neurally evoked contractions in the cryoinjured bladder strips suggesting that a cholinergic dominance occurs after cryoinjury. It is concluded that cryoinjury is a viable method of causing a defined, reproducible injury to the urinary bladder resulting in impaired function of both the cholinergic transmission and the smooth muscle. The bladder cryoinjury can be used as a model for studying impaired bladder compliance and detrusor contractility as well as treatments that may improve bladder function such as tissue engineering.

Adenosine Triphosphate↗