Correlative study of bufogenin constituents in venom of Bufo bufo gargarizans / 中国中药杂志

As known,simultaneous determination of various chemical indicators is one of the future trends in quality control of traditional Chinese medicines because of the extremely complex chemical compositions. This project is to screen the quality markers that can accurately control the quality of the Bufonis Venenum by exploring the intrinsic correlation of components. In this study,venom of Bufo bufo gargarizans from 17 different sources were used as research samples,and the contents of 7 bufogenin were determined by HPLC-DAD. Then,the data obtained were analyzed by Spearman correlation analysis and principal component analysis( PCA). In addition,a stepwise regression analysis was used to establish a predictive model for the contents of the seven bufogenin components( independent variable) and the total contents of the bufogenin( dependent variable). The results indicated that there is a significant positive correlation between the contents of telocinobufagin and cinobufotalin,and there is a significant positive correlation between the contents of bufalin,cinobufagin and resibufogenin. In contrast,the contents of telocinobufagin and cinobufotalin are negatively correlated with the contents of bufalin,cinobufagin and resibufogenin. However,the correlation between gamabufotalin and bufotalin and other components are not obvious. Furthermore,further study found that there is a correlation between the sum of the contents of bufalin,cinobufagin and telocinobufagin and the total contents of the bufogenin. In fact,the application of bufalin,cinobufagin and telocinobufagin as the quality control indicators of the Bufonis Venenum can better reflect the quality characteristics of the Bufonis Venenum compared with the previous quality control indicators. The conclusions will provide a reference for the revision of the quality standards of the Bufonis Venenum.

Expression of E-cadherin on bone marrow mononuclear cell surface and in plasma of patients with extra-myeloid leukemia and their clinical significance / 白血病·淋巴瘤

Objective To investigate the expression and clinical significance of soluble E-cadherin (sE-cad) and E-cadherin (E-cad) in acute leukemia (AL), and to explore their relationship with the pathogenesis,development and diagnosis of extra-myeloid leukemia. Methods 87 newly diagnosed or relapsed AL patients (19 cases of L1, 29 L2, 14 M2, 20 M3, 4 M4, 1 M5) were collected from hospitalized patients in hematology department of Harbin Medical University Cancer Hospital. The plasma from 20 healthy volunteers was used as control group. The bone marrow was from 15 non-AL patients hospitalized in hematology department (7 cases of thrombocytopenic purpura, 4 iron deficiency anemia, and 4 fever). The expression of sE-cad in the plasma of 47 patients and 20 healthy volunteers was detected by ELISA; the expression of E-cad on the membrane surface of bone marrow MNC in 40 patients and 15 controls was determined by flow cytometry. Results The plasma level of sE-cad in AL group was significantly higher than that in healthy control group [(66.812±52.712) ng/ml vs. (17.976±14.206) ng/ml, P<0.01]. The plasma level of sE-cad in extra-myeloid infiltration AL group was significantly higher than that in no-extra-myeloid infiltration AL group [(83.545±60.759) ng/ml vs. (42.152±22.043) ng/ml, P<0.01]. The plasma level of sE-cad in high leukocytes AL group was higher than that in no-high leukocytes AL group [(85.166±57.828) ng/ml vs. (41.933±32.064) ng/ml, P<0.05]. The percentage of E-cad expression in AL group was significantly lower than that in control group [(13.615±14.038) % vs. (31.700±16.213) %, P<0.01]. The percentage of E-cad expression in no-extra-myeloid infiltration AL group was significantly higher than that in extra-myeloid leukemia infiltration AL group[(18.691±14.917) % vs. (6.589±8.959) %,P<0.01]. The percentage of E-cad in no-high-leukocytes AL group was significantly higher in high leukocytes AL group [(20.925±12.081) % vs. (7.446±11.118) %, P<0.01]. Conclusions The expression of E-cad on the membrane surface of bone marrow MNC and the expression of sE-cad in plasma may be closely associated with the occurrence of extra-myeloid leukemia and leukocytosis, which may be one of the important molecular mechanisms of leukemic cell infiltration and leukocytosis. High expression of sE-cad in plasma can be treated as one of index to diagnose extra-myeloid leukemia.

Study on balance of process of alcohol precipitation of ganmaoling granules / 中国中药杂志

Ganmaoling granule is the first brand of domestic cold medicine sales, but its preparation method and process control parameters are relatively rough. Therefore it is urgent to upgrade the technologies of large varieties of traditional Chinese medicine (TCM). This paper focused on the balance between the remove of impurity and the retention of linarin during the process of alcohol precipitation of Ganmaoling granules. The effects of four factors on the process were investigated via single factor experiments. The results showed that the precipitating period, the initial ethanol concentration and the final ethanol concentration had a great effect on retention of linarin while the initial density of the extract has not. Similarly, the initial ethanol concentration, the final ethanol concentration and the initial extract density have a great effect on the yield of dry extract while the time of alcohol precipitation has not. The parameters of alcohol precipitation of Ganmaoling granules were optimized as 16 h of precipitating period, 95% ethanol as the initial reagent, 70% of the final ethanol concentration, and 1.10 of the initial extract density.

Modeling of thermal degradation of linarin during concentration process / 中国中药杂志

Ganmaoling granule, with annual sale of over one billion yuan, is the first brand of domestic cold medicine sales. As the only traditonal Chinese medicine（TCM） quality control indicator of Ganmaoling granule, linarin is thermally unstable. Its content will be changed significantly during the production process, which would then affect the quality of the finished product. In this paper, the law of degradation of linarin was investigated. The experimental results showed that degradation reaction of linarin belongs to the first reaction characteristics. The effective methods to reduce the loss of linarin would be realized fortunately by strictly controlling the heating temperature or shortening the heating time.

On-line monitoring of extraction of coldrine by near-infrared spectrum / 中国中药杂志

Extraction of the four Chinese herbals is the beginning step of the production process of coldrine granules and influences on drug quality significantly. In this paper, the on-line near infrared spectrum was collected during the extraction process of coldrine and then pre-processed by the first derivative. Partial least square regression (PLSR) model was developed for the quantity indicators of linarin, chlorogenic acid and solid content, according to results of both HPLC and weight-loss as reference methods. The correlation coefficient, root mean square error of cross-validation (RMSECV), root mean square error of calibration (RMSEC) and root mean square error of prediction (RMSEP) were used to optimize model parameters and confirm their performance. Correlation coefficients of three quality control indicator models reached more than 0.95.Values of RMSEC of linarin, chloroenic acid and solid content were 0.010 4, 0.009 34 and 0.055 5, respectively. And the values of RMSEP were 0.009 47, 0.142 and 0.008 42, respectively. The models, built on-line analyze data, revealed that the correlation coefficients of predicted values and measured values were greater than 0.97 and values of RSEP of linarin, chloroenic acid and solid content were 8.14%, 8.17% and 9.86%, respectively. The results showed that the NIR method could achieve the on-line detection and real-time monitoring of multi-indexes during the extraction process of coldrine. The technology could be used for drug quality control in the process of practical production, reducing the batch differences and ensuring pharmaceutical quality stability. In addition, it could provide real-time production data for subsequent product quality backtracking.

Flow Starting Point and Voiding Mechanisms Measured by Simultaneous Registrations of Intravesical, Intra-abdominal, and Intraurethral Pressures in Awake Rats / 대한배뇨장애요실금학회지

PURPOSE: The aim of this study was to apply a new surgical procedure that allows for the successful monitoring of intraurethral pressure (IUP) changes in the cystometry of awake Sprague-Dawley rats. METHODS: Twenty-six female Sprague-Dawley rats were grouped according to the catheterization method (bladder only; bladder and urethra; or bladder, urethra, and abdomen). Using an arbitrarily determined initial point of the first phase among four rat micturition phases on the simultaneous curves as a reference point, we compared the time differences to the points on an intravesical pressure (IVP) and those on IUP or a detrusor pressure (DP) curve from intra-abdominal pressure (IAP). RESULTS: In awake rat, the start of urethral flow on IUP curve corresponded to the initial point of the second phase, which is same to the results on the anesthetized rat. However, certain results, such as micturition pressure (MP) and intraluminal pressure high-frequency oscillations (IPHFOs), differed between awake and anesthetized rats. Most MP values were checked after the end of urethral flow on the IUP curve, which is due to the peculiar methodology such as transvesical catheterization. Urethral flow was not completely interrupted during the IPHFOs, which suggests the presence of urethral wall tension against the flow during voiding. After removal of the superimposed effects of IAP from IVP, the DP curve clearly showed a peculiar shape, highlighting the possibility of using IAP in place of IUP to detect the flow starting point on the IVP curve. CONCLUSIONS: Awake rat cystometry results have been interpreted based on those in anesthetized rats. However, our awake cystometry data were substantially different in terms of voiding time compared to those of anesthetized rats. This discovery warrants careful interpretation of the voiding parameters in awake rat cystometry.

Screening based on response surface methodology of multi-fractions traditional Chinese medicine with anti-influenza virus neuraminidase activity: take shuanghuanglian injection as an example / 药学学报

This study aimed to establish a novel method to screen out the combined components of multi-fractions traditional Chinese medicine (TCM), so that the internal relationship between multi-ingredients could be objectively assessed and the proportioning ratio could be optimized. Taking antiviral effect on neuraminidase activity of influenza virus as the evaluating indicator and using Box-Behnken response surface methodology, the main effective ingredients of Shuanghuanglian injection (SHL) were screened. Meanwhile, the relationship between active ingredients was discussed. Taking SHL as a comparison, the optimum proportioning ratio was predicted. The results indicated that chlorogenic acid, cryptochlorogenic acid, caffeic acid and baicalin have comparatively strong antiviral activity against influenza virus. Moreover, antagonistic action existed between chlorogenic acid and cryptochlorogenic acid, whereas synergistic action between caffeic acid and other components. The optimum proportioning ratio resulted from fitted model is: chlorogenic acid, cryptochlorogenic acid, caffeic acid and baicalin (107 microg x mL(-1) : 279 microg x mL(-1) : 7.99 microg x mL(-1) : 92 microg x mL(-1)). The antiviral activity of the recombined components is stronger than that of SHL, which was consistent with the experiment results (P < 0.05). Box-Behnken response surface methodology has the advantages of general-screening, high-performance and accurate-prediction etc, which is appropriate for screening the combined components of multi-fractions TCM and the optimization of the proportioning ratio. The proposed method can serve as a technological support for the development of modern multi-fractions TCM.

Transvaginal Cystocele Repair by Purse-String Technique Reinforced with Three Simple Sutures: Surgical Technique and Results / 대한배뇨장애요실금학회지

PURPOSE: Different techniques for cystocele repair including the conventional anterior colporrhaphy and mesh technique are known. Our goal was to evaluate the anatomical success and safety of our method of transvaginal anterior vaginal wall repair by the purse-string technique reinforced with three simple additional sutures in the repair of cystocele over a 4-year follow-up period. METHODS: This was a retrospective review of 69 consecutive patients (grades 2 to 4) who underwent the above operations between 2001 and 2011, including their success rates as assessed by use of the Baden-Walker halfway classification system. RESULTS: Of the patients, 62 patients (98%) were completely cured of cystocele and 1 patient showed grade 2 cystocele recurrence that required no further treatment. Two patients with grade 4 cystocele were completely cured. There was no vaginal erosion related to the cystocele repair. CONCLUSIONS: Transvaginal anterior colporrhaphy by a purse-string technique reinforced with simple additive sutures appears to be a simple, safe, and easily performed approach in cystocele repair. There is no need for other material for reinforcement, even in high-grade cystocele, which is an advantage of our technique.

Optimization of alcohol precipitation process for extract of Carthamus tinctorius by multiple guidelines grading method / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the optimal alcohol precipitation parameters for extract of Carthamus tinctorius.</p><p><b>METHODS</b>The effects of different factors on the transfer rate of hydroxy safflower yellow A (HSYA) was studied via single factor experiments, including the final alcohol concentration of the liquor, the speed of stirring, the initial density of the extract, the temperature and the pH of the liquor. Based on the results of single factor experiments, the final alcohol concentration of the liquor, the speed of stirring, the initial density of the extract and the pH of the liquor were studied by an orthogonal test and a multiple guidelines grading method, and the transfer rate of HSYA, the yield and the purity of extract in the supernatant were used as comprehensive evaluation index.</p><p><b>RESULT</b>The optimal alcohol precipitation process of Carthamus tinctorius extract was as follows: the final alcohol concentration of the liquor 50%, the speed of stirring 500 r/min, the initial density of the extract 1.15 g/ml and the pH of the liquor 5.0.</p><p><b>CONCLUSION</b>The proposed alcohol precipitation process is convenient and steady with high transfer rate of HSYA, high yield and purity of extract in the supernatant.</p>

Time-Related Changes in Detrusor Overactivity in Awake Rats with Spinal Cord Injury Observed by Simultaneous Registrations of Intravesical and Intraabdominal Pressures / 대한배뇨장애요실금학회지

PURPOSE: To compare the physical characteristics of detrusor overactivity (DO) induced by intravesical infusion of saline in awake, sham rats and rats with chronic spinal cord injury (SCI), by simultaneous registrations of intravesical and intraabdominal pressures. METHODS: Male Sprague-Dawley rats, normal or with a spinal vascular clip at the level of Th9, were investigated cystometrically 1 and 4 weeks after SCI. Intra-vesical pressure (IVP) and intra-abdominal pressure (IAP) were recorded simultaneously to evaluate true DO. During the filling phase, the event of IVP rises, defined as increments that exceeded 2 cmH2O from baseline, were determined as DO according to the absence of simultaneous changes in IAP. RESULTS: All SCI rats exhibited DO during the filling phase, which was not shown in sham rats. The frequency and pressure of DO had a tendency to decrease with time. The DO frequency of SCI rats after 4 weeks (0.9+/-0.2 min(-1)) was decreased compared with that after 1 week (2.1+/-0.4 min(-1); P0.05). CONCLUSIONS: Cystometric studies in awake male SCI rats showed some significant changes in bladder function after SCI. All SCI rats exhibited DO during the filling phase, and showed different physical characteristics of DO over the course of time. The neurological basis of these time-related changes remains poorly understood, but may provide important prognostic information about long-term urological management in SCI patients.

Erratum: Urodynamic Findings in an Awake Chemical Cystitis Rat Model Observed by Simultaneous Registrations of Intravesical and Intraabdominal Pressures / 대한배뇨장애요실금학회지

No abstract available.

Early Sequential Changes in Bladder Function after Partial Bladder Outlet Obstruction in Awake Sprague-Dawley Rats: Focus on the Decompensated Bladder

PURPOSE: We investigated bladder function, with special focus on initial functional changes, by objective report of decompensated bladder according to the percentage of residual urine volume to bladder capacity in awake, obstructed rats. MATERIALS AND METHODS: Thirty rats were randomly subjected to sham operations (n=10) or partial bladder outlet obstruction (BOO, n=20). Cystometric investigations were performed without anesthesia 1 or 2 weeks after BOO surgery. To reduce the influence of confounding factors in awake cystometry, we used simultaneous recordings of intravesical and intraabdominal pressures. Decompensated bladder was defined as the bladder with more than 20% of residual volume compared with bladder capacity. RESULTS: Compared with that in sham animals, basal pressure was elevated in both BOO groups. Threshold pressure was higher in the 2 week BOO (p<0.01) group. Compliance was decreased in the 1 week BOO group (p<0.01) and increased in the 2 week BOO group (p<0.001). Bladder capacity was not increased in the 1 week BOO group, but was increased in the 2 week BOO group (p<0.01). Decompensation was found in 62.5% of the 1 week BOO group and in 33.3% of the 2 week BOO group. CONCLUSIONS: From the earlier phase, the bladders exhibited serial changes in pressure and volume parameters, and decompensated bladders defined by the percentage of residual volume to bladder capacity could be seen. During the later phase, there was an increasing tendency of compensated bladders, accompanied by the bladders being enlarged and more compliant.

Dissimilar Effects of Tolterodine on Detrusor Overactivity in Awake Rats with Chemical Cystitis and Partial Bladder Outlet Obstruction / 대한배뇨장애요실금학회지

PURPOSE: We investigated bladder function, with a special focus on nonvoiding contractions (NVCs), in awake rats with chronic chemical cystitis and bladder outlet obstruction (BOO) by use of simultaneous registrations of intravesical and intraabdominal pressures. In addition, we tested the effects of tolterodine on the NVCs in these models. METHODS: A total of 20 female Sprague-Dawley rats were used in this study. In eight rats, chemical cystitis was induced by intravesical instillation of HCl. Twelve rats were subjected to sham instillations or partial BOO. Four weeks after intravesical instillation or 2 weeks after partial BOO, cystometrograms were obtained by use of simultaneous recording of intravesical and intraabdominal pressure in all unanesthetized, unrestrained rats in metabolic cages. RESULTS: A total of 17 rats survived. In the rats with acute injury by HCl, 50% showed detrusor overactivity (DO), which was not seen in the sham group. The cystitis group had lower DO pressure without a difference in DO frequency compared with the BOO group. After the administration of tolterodine, the cystitis group showed no difference in DO frequency or pressure, whereas the BOO group showed decreased values for both parameters. CONCLUSIONS: Our study showed that toleterodine produced no effect on DO during the filling phase in rats with chronic chemical cystitisbut decreased the frequency and pressure of DO in rats with BOO. Clinically, studies are needed to improve the treatment effect of anticholinergic drugs ininterstitial cystitis patients with overactive bladder.

Development and Changes with Age of Detrusor Overactivity in Spontaneous Hypertensive Rats as Observed by Simultaneous Registrations of Intravesical and Intraabdominal Pressures / 대한배뇨장애요실금학회지

PURPOSE: Overactive bladder is especially common in the elderly, although it is not regarded as a normal part of aging. Thus, we investigated how aging alters the cystometric and detrusor overactivity (DO) parameters and the density of nerve growth factor (NGF) in awake spontaneous hypertensive rats (SHRs) of different ages. METHODS: Three age groups of 12- (n=5), 17- (n=6), and 21- (n=6) week-old SHRs (Oriental Bio Inc.) were used. A catheter was implanted into the bladder to record the intravesical pressure (IVP), and a balloon-fitted catheter was positioned in the abdominal cavity to record the intraabdominal pressure (IAP). Of the IVP elevations above 2 cm H2O, DO was defined as a rise in IVP without a simultaneous change in IAP and was counted during the filling phase. We measured the expression of NGF in the bladders by enzyme-linked immunosorbent assay. RESULTS: Both the body and bladder weights significantly increased with age, but the normalized ratio between those was not changed. As for DO, none of the12-week-old rats showed DO, whereas the other groups did. DO increased significantly with age (P=0.0045 by Mantel-Haenszel trend test), although no significant differences were found in DO frequency or pressure between the 17- and 21-week-old age groups. NGF did not show any significant differences among the three groups. CONCLUSIONS: Our results showed that SHRs begin to shows DO after a certain age, such as 12 weeks of age, and that the occurrence of DO has a close relationship with aging. However, NGF, which is known to be increased in the bladder wall of patients with overactive bladder, did not show any relationship with aging in this study.

Urodynamic Effects of Propiverine on Detrusor Overactivity and Abdominal Straining during Voiding in Awake Rats with Intravesical Prostaglandin E2 Instillation

PURPOSE: We investigated the effect of propiverine on cystometric parameters based on intraabdominal pressure (IAP) in awake rats in an overactive bladder (OAB) model induced by intravesical instillation of prostaglandin E2 (PGE2). MATERIALS AND METHODS: Twenty-two female Sprague-Dawley rats were used. Polyethylene catheters were implanted into the bladder to record the intravesical pressure (IVP) and into the femoral artery to administer medication. A balloon-fitted catheter was positioned in the abdominal cavity to record the IAP. Awake cystometries were performed before and after intraarterial administration of propiverine 1 mg/kg (n=6), intravesical administration of 50microM PGE2 only (n=6), or intravesical PGE2 plus 1 mg/kg (n=4) or 3 mg/kg (n=6) of intraarterial propiverine. Cystometric pressure and volume parameters and variables related to detrusor overactivity (DO) were investigated. RESULTS: Rats administered intravesical PGE2 showed increased pressure parameters and decreased volume parameters comparable to the DO model, which was effectively prevented by propiverine (1 or 3 mg/kg). Typical DO shown during the filling phase was decreased by intraarterial propiverine (3 mg/kg) injection. After propiverine (3 mg/kg) injection, IAP was increased at the time of micturition pressure with or without threshold pressure (p<0.05, p<0.01) depending on the dose administered. CONCLUSIONS: Propiverine improved pressure- and volume-related parameters in an OAB model. Furthermore, it also decreased the frequency of DO. However, higher concentrations of propiverine induced straining voiding.

Intravesical PGE2 Administration in Conscious Rats as an Experimental Model of Detrusor Overactivity Observed by Simultaneous Registrations of Intravesical and Intraabdominal Pressures / 대한배뇨장애요실금학회지

PURPOSE: The urodynamic effects of intravesical PGE2 instillation on bladder function and detrusor overactivity (DO) during the filling phase were investigated in rats by measuring intraabdominal and intravesical pressures simultaneously. MATERIALS AND METHODS: Continuous cystometry was performed inconscious, female and male Sprague- Dawley rats. We investigated pressure-, volume-, and DO-related parameters. RESULTS: Intravesical instillation of PGE2 increased all pressure-related parameters and decreased volume-related ones, compared to the control cystometric ones. However, among the total number of intravesical pressure rises (IVPRs) above 2 cmH2O during the filling phase, only 33% in female rats and 38% in male rats after PGE2 instillation were identified as true DO during the filling phase. CONCLUSIONS: Our findings suggest that the rat model with intravesical PGE2 is inappropriate for observing the effects of some drugs or mechanisms on DO, because only approximately 30% of IVPRs were confirmed as true DO. However, this model of intravesical PGE2 instillation has some advantages for the observation of changes in pressure and volume parameters rather than in DO-related ones.

Urodynamic Findings in an Awake Chemical Cystitis Rat Model Observed by Simultaneous Registrations of Intravesical and Intraabdominal Pressures / 대한배뇨장애요실금학회지

PURPOSE: The aim of this study was to investigate the effect of urinary bladder inflammation on bladder function in a rat chemical cystitis model. We also histologically confirmed the effects of inflammation in the detrusor on chronically inflamed bladder in rats. MATERIALS AND METHODS: A total of 13 female Sprague-Dawley rats were used in this study. In seven rats, intravesical instillation of HCl induced chemical cystitis, and the other rats with intravesical instillation of saline were used as the sham. After 2 weeks, cystometrograms were obtained with additional intraabdominal pressure measurements in all unanesthetized, unrestrained rats in metabolic cages. The rats were killed just after cystometry. The bladders were removed and examined histologically for mast cells and inflammatory changes. RESULTS: The rats with acute injury by HCl showed no differences in pressure parameters, including basal pressure, threshold pressure, and maximum bladder pressure, compared with the sham rats. They showed significantly increased bladder capacity, micturition volume, residual volume, and micturition interval compared with the sham group. They also showed an increased frequency of detrusor overactivity compared with the sham group. The percent of detrusor overactivity was 56.3% among the total intravesical pressure rises above 2 cmH2O. The histological findings of the rats with acute injury by HCl were consistent with chemical cystitis. CONCLUSIONS: Overlapping patterns of lower urinary tract symptoms and pelvic pain are common disease characteristics among interstitial cystitis patients. The situation in an animal model of interstitial cystitis is similar, as observed in this study by the histologic and awake cystometric examinations. However, the interstitial cystitis model showed detrusor overactivity during the filling phase without a decrease in bladder capacity and micturition intervals, which differs from the characteristics of overactive bladder patients.

The Effect of Suprapubic Magnetic Stimulation in Patients with Neurogenic Detrusor Overactivity

PURPOSE: To evaluate the effect of suprapubic magnetic stimulation (SMS) with the use of an arm-type magnetic stimulator for the treatment of patients with neurogenic detrusor overactivity. MATERIALS AND METHODS: Eleven patients with neurogenic detrusor overactivity were enrolled in this study. All patients underwent more than 16 SMS sessions, two times per week, with the use of an arm-type magnetic stimulator. Objective success was defined as a significant reduction (> or =50%) in the total number of leakage episodes per 24 hours, whereas subjective success was defined as the request to continue treatment. RESULTS: Five (71.4%) of 7 patients who had urinary incontinence before treatment reported objective success, and 3 patients showed no incontinence. A total of 6 (75.0%) of 8 patients showed increased average voiding volume. One patient showed an adverse effect of back pain after SMS and dropped out. Seven patients (70.0%) of 10 patients wanted to continue this treatment. They showed significant improvements in frequency/volume chart data, quality of life scores, and urodynamic data. CONCLUSIONS: SMS can be a safe, non-invasive and effective option for the treatment of neurogenic detrusor overactivity.

The Effect of tolterodine Via Oral and Intravenous Administrations on Voiding in Awake Spontaneously Hypertensive Rats as an Overactive Bladder Model

PURPOSE: We investigated the effect of oral or intravenous tolterodine on cystometric parameters in awake spontaneously hypertensive rats (SHRs) as a model of overactive bladder (OAB). The aim of our study was to observe the experimental conditions required to reproduce the clinical pharmacological effects of tolterodine, as seen in humans, to decrease bladder pressure or increase bladder capacity. MATERIALS AND METHODS: We studied the effects of the most widely used antimuscarinic drug, tolterodine, on cystometric parameters via two different administrations (oral and intravenous) in awake SHRs. RESULTS: Oral administration of tolterodine 10 mg/kg(-1) body weight in awake rats did not change any cystometric parameters significantly. Intravenous administration of tolterodine 0.3 mg/kg(-1) body weight significantly decreased basal pressure (BP) and micturition pressure (MP), but showed no effect on micturition interval (MI) or bladder capacity (BC). CONCLUSION: Despite a high dose of tolterodine via an oral or an intravenous route, a decrease in BP or MP was the only effect on cystometrographic parameters in awake rats, whereas MI and BC were not significantly affected. Therefore, it is difficult to reproduce in awake rats as an acute response the cystometric increase in the MI that is observed in humans after chronic administration of antimuscarinic agents.

Application and Limitations of Awake Cystometry in Sprague-Dawley Rats with Partial Bladder Outlet Obstruction as a Model of Overactive Bladder or Obstruction

PURPOSE: Partial bladder outlet obstruction (PBOO) in rats leads to changes in bladder function, such as obstruction and detrusor overactivity (DO). The aim of our study was to observe factors essential for the objective descriptions of PBOO rats as an overactive bladder model as well as an obstruction model under awake cystometry. We also aimed to investigate the urodynamic effects of PBOO objectively in view of DO-related parameters as well as conventional pressure and volume-related parameters. MATERIALS AND METHODS: PBOO was produced in 10 female Sprague-Dawley rats by ligating the proximal urethra over a 0.9 mm metal rod; 10 sham-operated rats were used as controls. Intravesical pressure (IVP) was recorded via an open catheter in the bladder, and intraabdominal pressure (IAP) via an intraabdominal balloon catheter. Continuous cystometry was performed 2 weeks after the PBOO procedure. Conventional and newly developed DO-related urodynamic parameters were investigated. RESULTS: PBOO led to a significant increase in bladder weight. Three rats showed the picture of decompensated bladder and were excluded from the analysis. The obstructed group showed some increased pressure- and volume-related parameters. They showed a DO frequency of 1.5+/-0.3/min, but the sham group did not. CONCLUSIONS: Our results showed that bladder decompensation can happen after PBOO, and we need to describe those exclusions accurately in reports. In conscious PBOO rats, simultaneous registration of IAP and IVP is needed for accurate investigations of DO, because PBOO can lead to DO as well as bladder hypertrophy.