Progress ofβ3-Adrenoceptor Agonists in the Treatment of the Overactive Bladder / 天津医药

The overactive bladder syndrome (OAB) is a prevalent condition among adults. Currently, the present treatment is mainly conservative therapy. Antimuscarinic drugs are currently the first-line treatment for OAB. However, many patients experienced insufficient therapeutic benefit and/or unpleasant side effects. Recent advances in the understand-ing of the physiopathology of OAB have driven a huge amount of basic and clinical research into novel pharmacological com-pounds.β3-adrenoceptor agonists are an emerging drug class for the treatment of the OAB. This study reviewed the pharma-cological profile ofβ3-adrenoceptor agonists and discussed the efficacy, safety and tolerability.

Overactive bladder symptom score to evaluate efficacy of solifenacin for the treatment of overactive bladder symptoms / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Overactive bladder (OAB) is a series of symptoms with high prevalence in elderly people. This study was conducted using the overactive bladder symptom score (OABSS) to evaluate the efficacy of solifenacin succinate for the treatment of OAB.</p><p><b>METHODS</b>This was a prospective, multicenter, single-arm, 12-week study that enrolled 241 OAB patients. The patients received 5-10 mg/day solifenacin. Changes in OABSS, symptoms from voiding diary, perception of bladder condition (PPBC) score, international prostate symptom score (IPSS) and quality of life (QOL) were evaluated at weeks 0, 4, and 12. The relationship between OABSS and PPBC score or parameters of voiding diary was also evaluated.</p><p><b>RESULTS</b>At baseline, the mean OABSS for all patients was 9.41 ± 2.40, and was reduced significantly at week 12 (-3.76 points; 61.21%, P < 0.0001). The OABSS subscore, PPBC score, IPSS, and QOL were also significantly reduced during the study (P < 0.0001). The overall incidence of adverse events was 19.91% (44 cases). The gastrointestinal system was the most commonly affected (11.31%). Around 5.88% of the cases had adverse events related to the genitourinary system. There was a strong correlation between OABSS and urinary symptoms that was recorded in the 3-day voiding dairy.</p><p><b>CONCLUSIONS</b>We showed that solifenacin was clinically effective for relieving OAB symptoms, considering the balance between efficacy, patients' well-being, and tolerability. OABSS integrates four OAB symptoms into a single score and can be a useful tool for research and clinical practice.</p>

Effects of immunosuppressants on co-stimulated lymphocyte's Th1/Th2 cytokine production / 中华泌尿外科杂志

Objective To analyze the effect of cyclosporin A(CsA), rapamycin(RPM) and macophenolic acid(MPA) on the co-stimulated lymphocytes, CD28 and CD40, and their production of Th1/Th2 cytokine, IL-2, IFN-γ, IL-4, IL-10 and IL-12. Methods The experimental groups were divided into ①mono-stimulating and co-stimulating groups: CD3 mAb mono-stimulating (group a),CD3 mAb+CD28 mAb co-stimulating (group b), CD3 mAb+CD28 mAb+CD40 L mAb co-stimulating(group c), CD3 mAb+CD28 mAb+CTLA4 mAb co-stimulating (group d). ②CsA groups: 300 ng/ml of CsA was added to group a, b, c and d. ③RPM groups: 300 ng/ml of RPM was added to group a,b, c and d. ④MPA groups:300 ng/ml of MPA was added to group a, b, c and d. The cytokine production was measured by ELISA.Results The co-stimulated CD28 and CD40 Th1/Th2 cytokines production of IFN-γ, IL-2, IL-4 and IL-10 were significantly increased. Compared with group a, IFN-γ increased from (248.91±11.20)ng/ml to (555.08±24.42)ng/ml and (548.19±33.06)ng/ml, IL-2 increased from (29.48±8.61)ng/ml to (1100.82±99.29)ng/ml and (842.23±29.31)ng/ml, IL-4 increased from (32.29±6.76)ng/ml to (116.02±15.03)ng/ml and (147.28±18.07)ng/ml, IL-10 increased from (147.01±10.47)ng/ml to (291.79±12.47)ng/ml and (302.52±35.18)ng/ml,respectively, P＜0. 01. Compared group b with group c, the Th1 cytokines production was decreased.IL-2 and IL-12 decreased (P＜0.05). The Th2 cytokine IL-4 production was increased (P＜0. 05).CTLA4 mAb and three other immunosuppressants, CsA, RPM and MPA, inhibited co-stimulated lymphocyte's both cytokines Th1 and Th2 production. The inhibitory effect of CsA on Th1/Th2 cytokine production was more significant than RPM and MPA did. The co-inhibitory effect of CTLA4 mAb and CsA was observed as well. The increased co-stimulated CD28 and CD40 IL-12 production could be suppressed by MPA. CsA and RPM had no inhibitory effect on the IL-12 production.Conclusions CD28/CD40 co-stimulatory pathway plays the key role in lymphocyte activation and Th1/Th2 cytokine production. CsA, RPM and MPA can inhibit co-stimulated lymphocyte's Th1 and Th2 cytokine production. CsA and CTLA4 mAb have co-inhibitory effect on co-stimulated lymphocyte's Th1/Th2 cytokines production. CD40 L mAb decreases the Th1 cytokines production(including IL-12) and increases the Th2 (mainly IL-4) production, which may be the mechanism of its longevity effect on allograft.

Implication of androgen receptor gene methylation in transformation of hormone-resistance in prostate carcinoma / 中华泌尿外科杂志

Objective To study the mechanisms underlying this loss of AR expression in rat prostate cancer. Methods The methylation status of the AR gene promoter region in rat prostate cancer and cell lines (PLS10,20,and 30) was investigated by Southern blotting,methylation-specific polymerase chain reaction,and methylation-sensitive single-strand conformation analysis (MS-SSQA). Results AR mRNA expression was not detected in any of the rat prostate cancers or cancer cell lines tested by Northern blot analysis. Higher levels of methylated CpGs were observed in PLS20 than that in PLS10 or 30. Demethylation treatment by 5-aza-2’-deoxycytidine restored AR mRNA expression in PLS20.The CpGs was suggested to be responsible for AR expression in rat prostate cancer,and found to be located-9 and-1 nucleotides upstream of the transcriptional initiation site.All of the examined rat prostate and seminal vesicle cancers demonstrated hypermethylation at these CpG sites. Conclusions These data clearly demonstrate that aberrant hypermethylation in the AR promoter region may play a critical role in AR expression in rat prostate cancers.Loss of AR expression might result in development of hormone-resistant prostate carcinoma.

Establishment of transplantable rat prostate carcinomas and study of its relationship to hormone dependency / 中华泌尿外科杂志

Objective To establish transplantable rat prostate carcinoma and study its relationship to hormone dependency. Methods Six transplantable rat prostate carcinoma lines were established from primary tumors developing in the dorsolateral prostate of F344 rats receiving a combined treatment with 3, 2’-dimethyl-4-aminobiphenyl (DMAB) and testosterone propionate (TP). Results Growth in the subcutis of nude mice (ICR-nu/nu) is rapid with a doubling time of approximately 10 days and transplantability is 100%. The histological appearance of the transplanted tumors is very similar to that of the primaries and their structures have not been altered by after 8 passages. Androgen receptor immunohistochemistry revealed all to be negative. Conclusions These data indicate that the model should prove useful for studies of invasion, metastasis, and hormone dependency of prostate carcinomas.

Advances in clinical study of nocturia / 北京大学学报(医学版)

Nocturia is one of the most common reasons for interrupted sleep in general adult population.The condition affects both men and women,with an incidence that increases dramatically with age.Nocturia has a negative impact on quality of life,affecting both morbidity and mortality.International Continence Society(ICS) issued a report of terminology standardization in 2002,in which nocturia is defined as waking during the night at least once to urinate.Nocturia is a common complaint in elderly population.Although most cases of nocturia are assumed to be caused by urologic problems,the interacting effects of aging and sleep on renal and urinary function,in fact,cause nocturia in the elderly.Effective diagnosis of the condition is dependent on a clear understanding of its underlying etiology.Multiple factors may cause nocturia,such as behavioral or environmental factors and pathologic conditions.In general,the causes of nocturia fall into three categories:diurnal polyuria,nocturnal polyuria,and low bladder capacity.Careful evaluation of medications and underlying medical conditions is essential for the proper management of nocturia.A voiding diary is necessary to diagnose the syndrome of nocturnal polyuria,which is a common cause of nocturia.Addressing any underlying conditions that contribute to nocturia is the first step in treating the condition.Lifestyle and behavioral changes may provide benefit in some individuals,but for many cases,pharmacotherapy is the best option.Antimuscarinic agents are first-line therapies for overactive bladder and are often used in the management of nocturia.Current treatment options also include desmopressin,a synthetic analog of arginine vasopressin,which can increase urinary osmolality and decrease total urinary volume.The desmopressin therefore increases the length of time until the first nocturnal void and decreases the number of nocturnal voids,the NUV voided,and the percentage of urine voided at night.

Development of remote wireless mobile voiding diary and a report of its objective voiding in 20 young people / 北京大学学报(医学版)

Objective:To find out the data of the micturitions in healthy young people with the remote & mobile voiding diary monitoring system.Methods:Twenty healthy young people were studied and ten of them were female.The ages ranged from 22 to 35 years(the mean age:27.4 years).The females were 22-33 years old(the mean age:26.4 years) and the males 24-35 years old(the mean age:28.4 years).With the remote & mobile voiding diary monitoring system,their voiding information was collec-ted.Through bluetooth,the voiding information was sent to the patient's intelligent cell phone from the collector,then stored directly by intelligent cell phone and wirelessly transmitted to the workstation in the hospital.All of them completed the voiding diaries for 7 days and the data were analyzed.Results:The average micturition of the young healthy people was 5.6 times(3.4-7.4) per 24 hours,in which 5.3(3.4-7.3) times were in the daytime and 0.3(0-1.3)times in the night.The functional voiding vo-lume was 318 mL(66-642 mL).The mean voiding volume in 24 hours was 1 724 mL(1 152-2 415 mL),in which 1 289 mL(786-2 039 mL) was in the daytime and 435 mL(292-805 mL) in the night.The mean drinking volume was 1 022 mL(453-1 721 mL)in the daytime and 7 mL(0-43 mL) in the night.The nocturia index(Ni)was 1.03,the nocturnal polyuria index(NPi) 26%,and the nocturnal bladder capacity index(NBCi) 0.27.Conclusion:The remote & mobile voiding diary monitoring system can help us get the objective voiding information from young health people for the first time.It is reliable,maneuverable and can be widely used in clinical diagnosis.

The histopathologic features of rat bladder with capsaicin intravesical instillation / 中华泌尿外科杂志

0.05).Morphology showed slight dilation of the vessels in the superficial part of lamina propria in the 100 ?mol/L capsaicin group.In the group treated with 2 mmol/L capsaicin,erosion of the mucosa,edema and capillary distention in the lamina propria were seen as well as focal damage to the superficial muscle near the lamina propria.This led to hematuria in the early stage.The mucosal changes started to heal after 1 week and returned to normal after 8 weeks.Conclusions In rats,intravesical capsaicin instillation at a dose of 100 ?mol/L appears to be a safe method of treatment.High doses of capsaicin may result in some reversible damages of the mucosa and inflammatory changes of the bladder.

Experimental studies of adrenergic fibers and vesicoureteral reflux / 中华泌尿外科杂志

Objective To evaluate the correlation between vesicoureteral reflux (VUR),age,and bladder catecholamine content in rats. Methods Forty-five Long-Evans rats were divided into three groups: fifteen were babies,fifteen were adults,and fifteen were old retired breeder rats. The animals were placed in a supine position,the peritoneal cavity was opened, both ureters were exposed to be observed under the Zess model surgical microscope.A TelcoTm striped 24 G 3/4 in.I.V.catheter placement unit was punctured into the vertex of the urinary bladder.The needle was then withdrawn and the bladder was emptied.The bladder pressure was subsequently monitored by means of a Beckman polygraph via a Bentley physiological pressure transducer.The Teflon catheter was also connected with an infusion withdrawal pump (Haverd type 936). The connective tube was warmed with a simple light bulb. Methylene blue solution (10 mg+19 ml saline) was used as a developing dye at an infusion rate of 0.116ml/min. Likewise,both ureters and the urethral orifice were carefully observed.The pressures at reflux,the pressure at leakage point were recorded.The bladder catecholamine contents were determined with a radioenzymatic assay. Results None of the baby rats showed reflux, 60%(9/15)adult rats had VUR.Dopamine and epinephrine contents were higher in baby rats and decreased as the animal aged. Conclusions High levels of dopamine and epinephrine at weaning stage could compensate to prevent VUR before nerve maturity.

Intravesical instillation of resiniferatoxin for the treatment of overactive bladder / 中华泌尿外科杂志

Objective To evaluate the clinical outcomes of intravesical instillation of resiniferatoxin (RTX) for the treatment of overactive bladder(OAB). Methods 30 patients (28 females and 2 males) included in the study.The mean age was 39 years (range,21 to 60 years).The mean course of the illness was 6.9 years (range,2 to 30 years).The voiding diaries of pretreatment showed that frequency at day time varied from 9 to 26 times with a mean of 15.0 times;frequency at night ranged from 3 to 13 times with a mean of 6.4 times.Of the 12 patients undergoing cystoscopy 10 had chronic inflammation in both mucous and submucous.Based on biopsy 1 case was pathologically diagnosed as glandulous cystitis,2 as interstitial cystitis,and others as chronic inflammation.100 ml of RTX at a concentration of 100 nmol/L was intravesically instillated in all the patients and was retained within the bladder for 30 minutes. Results RTX instillation had no vesical irritation and other adverse effects,and no local anesthesia was required.The symptoms were improved immediately in all the patients after 1 day of RTX intervention.The decreases in both diurnal (5 to 15 times,mean 8.9 times) and nocturnal (0 to 5 times,mean 3.0 times) frequencies were significant(P

A preliminary evaluation of VISER testing in the diagnosis of ED / 中华泌尿外科杂志

Objective To evaluate VISER as a non invasive monitoring of penile cavernosal pressure for the diagnosis of ED. Methods With the use of AVSS and papaverine ICI,39 cases,including 32 patients of ED and 7 controls,were tested with VISER device. Results 7 controls and 13 ED cases (40%) have achieved a valid erection by AVSS alone while another 13 ED cases required papaverine ICI (10 mg) for successful erection whereas 6 of ED cases failed what so ever. The VISER testing showed the erection data and peak data indexes, especially in total energy of erection and peak, were higher in controls than ED groups except the average duration of erection being longer in ED papaverine group. Conclusions VISER is an accurate system for measuring the changes of intracavernosal pressure in dynamic state during penile tumescence. The use of eye glasses TV monitor can help enhance the effectiveness of AVSS and lower the dosage of vasoactive drugs.VISER testing is non invasive,accurate and easy to perform and might serve as a screening test for ED patients in the near future.

A preliminary study on intravesical capsaicin for the treatment of obstinate urethral syndrome / 中华泌尿外科杂志

Objective To evaluate intravesical capsaicin for the treatment of obstinate urethral syndrome in female. Methods Thirty two female patients suffering from urethral syndrome not relieved on various therapeutic methods for a long time were treated by bladder instillation of 100 ml of 100 ?mol/L capsaicin. Results 15 cases were followed up for more than 12 months with improvement in 94%.The symptoms were totally disappeared in 33% of the patients.The syndrome recurred in 53% between 3～6 months. 1 case did no response to the treatment. Bladder instillation of capsaicin induced an increase of the bladder volume.Some burning sensation was the only side effect. Conclusions Intravesical capsaicin could be a long lasting effective therapeutic method for patients with obstinate urethral syndrome.

Application of capsaicin for preventing unstable bladder after suprapubic prostatectomy / 中华泌尿外科杂志

Objective To evaluate the application of capsaicin to improve bladder stability after suprapubic prostatectomy for BPH. Methods 40 patients with BPH underwent suprapubic prostatectomy under epidural anesthesia were randomly divided into A?B?C and D groups (n=10 in each group).Capsaicin of 1 mmol/L was instilled into the bladder preoperatively for 30 minutes in group B and group D had 10 ml of 1 mmol/L capsaicin given epidurally.Group A and Group C received saline only. Results The bladder instability was lessened.The time of bladder perfusion clearance,indwelling catheter delivery,duration of cystospasm and number of postoperative cystospasm cases in group B and D reduced significantly as compared with group A and C.The Pdet and volume were improved significantly,the Qmax and residual urine were also improved. Conclusions The intravesical and epidural capsaicin delivery helps to prevent detrusor instability and reduces the pain caused by postoperative cystospasm.It also improves the bladder function deteriorated by BPH.