Effects of sensory neuron-specific receptor agonist on bladder function in a rat model of cystitis induced by cyclophosphamide

Purpose

To investigate the effects of activation of sensory neuron-specific receptors (SNSRs) on cyclophosphamide (CYP) bladder overactivity in rats.

Methods

Female Sprague–Dawley rats (235–258 g) were used. Rats were injected with either CYP (200 mg/kg, intraperitoneally) or saline (control). Continuous cystometrograms (0.04 ml/min) were recorded 48 h after CYP or saline injection under urethane anesthesia. After stable micturition cycles were established, a selective rat SNSR1 agonist, bovine adrenal medulla 8-22 (BAM8-22), was administered intravenously or intrathecally.

Results

Cyclophosphamide treatment-induced higher baseline pressure and shorter intercontraction intervals compared with the control group. Intravenous administration of BAM8-22 at 10, 30 and 100 μg/kg significantly increased intercontraction intervals in the CYP-treated group. Intrathecal administration of BAM8-22 at 0.03, 0.1 and 0.3 μg also significantly increased intercontraction intervals in the CYP-treated group. Intravenous or intrathecal administration of BAM8-22 did not change baseline pressure or maximum voiding pressure in the CYP-treated group.

Conclusions

These findings indicate that activation of SNSRs can suppress CYP-induced bladder overactivity, probably due to suppression of bladder afferent activity.     

多功能评估工具尺的研制及临床应用

目的探讨多功能评估工具尺在临床护理评估中的应用效果。方法将120例手术患者随机分为对照组和观察组各60例。对照组采用传统纸质版护理评估单,观察组设计并制作多功能评估工具尺,对患者疼痛、压疮和深静脉血栓风险进行评估。结果观察组评估耗时显著短于对照组(均P0.01);92.31%护理人员愿意使用多功能评估工具尺,使用满意度得分率77.88%。结论多功能评估工具尺受到护理人员的认可,可节省风险评估时间,提高工作效率。     

Urodynamic assessment of bladder function.

Bladder function in micturition may be studied, without interference from the urethra, through 2 parameters, Piso and Q, which are measures respectively of the maximum pressure and of the maximum flow rate that the bladder can generate, i.e. of its intrinsic strength and speed. These parameters may be determined in a standard urodynamic investigation if the patient interrupts voiding for a short time with the external sphincter. The normal ranges of Piso and Q depend only slightly on age and sex and seem to be as follows: Piso, 50 to 100(+)cm H2O in both sexes; Q, 35 to 120 ml s-1 in males, 20 to 80 ml s-1 in females. There are significant differences in both parameters between different groups of patients. Many females, with stress or urge incontinence or with urgency, have bladders which seem to be weaker than normal (low Piso). The majority of proximally obstructed males, and many who have been surgically relieved of obstruction, have bladders which are significantly slower than normal but are of normal strength (low Q, normal Piso). Therefore the characteristic response of the detrusor to obstruction appears to be not the expected mechanical hypertrophy (Turner Warwick et al., 1973) but reduction in intrinsic speed. In contrast, a few proximally obstructed males and most males with a history of primary enuresis (persisting after 6 years of age) have bladders of normal speed and of strength significantly greater than normal (normal Q, high Piso), suggesting true mechanical hypertrophy of the detrusor. Females with a history of primary enuresis do not show this pattern so clearly. Since these sex- and disease-related differences must surely be of clinical significance, and since it is so easy to measure Piso and Q by the method given in section (e) of the Appendix, those who are concerned with clinical urodynamics are urged to investigate bladder function in this or some equivalent way (e.g. that proposed by Sch?fer and Melchior (1975)).     

Neuroselective current perception threshold evaluation of bladder mucosal sensory function

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

ATP及其受体P2X参与膀胱感觉的研究进展

P2X受体是非选择性门控阳离子通道,细胞外ATP是其天然配体,已经克隆的7个亚型在膀胱均有分布,其中P2X2、P2X3受体分布于感觉神经元、膀胱上皮细胞和上皮下传入神经纤维上。研究认为膀胱上皮细胞可释放ATP,作用于P2X2、P2X3受体参与膀胱的容量感觉、痛觉和排尿反射,现对这方面的研究进展作一综述。     

Reproducibility of non-standardised autonomic function testing in the pre-operative assessment screening clinic*

By convention, autonomic function tests are undertaken under standard test conditions that limit their implementation during routine pre-operative assessment. We therefore evaluated the comparability of autonomic function tests under both non-standardised and standardised test conditions in 20 healthy male subjects. Autonomic function was assessed using an ECG monitor and a continuous non-invasive blood pressure measurement device. Under non-standardised conditions, intraclass correlation for heart rate variability analysis was good for the low and high frequency bands (0.87; 95% CI 0.58-0.96 and 0.83; 95% CI 0.56-0.94, respectively), but moderate (0.65; 95% CI 0.14-0.86) for the very low frequency band; reproducibility was high for the expiration/inspiration ratio (0.89; 95% CI 0.71-0.96), Valsalva ratio (0.76; 95% CI 0.37-0.91) and handgrip test (0.76; 95% CI 0.35-0.91) (all p<0.05) but was low for the response to quick standing. Reproducibility under standardised conditions was comparable to the above values. We demonstrated that reproducibility for most autonomic tests under non-standardised conditions is acceptable and suggest that implementation of these tests during pre-operative assessment may be feasible.     

Effects of streptozotocin-induced diabetes on bladder function in the rat

Streptozotocin-induced (STZ, 60 mg./kg. I.V.) diabetic male rats underwent cystometrographic (CMG) and electrophysiologic evaluations under urethane anesthesia (1.2 gm./kg.) to determine whether the neural pathways to the urinary bladder are altered in these animals. Diabetic rats (n = 6) in comparison to controls (n = 8) had significantly greater micturition volumes (3.0 +/- 0.8 ml. vs. 0.7 +/- 0.4 ml., p less than 0.001), bladder compliances (0.51 +/- 0.15 cm. H2O/ml. vs. 0.12 +/- 0.09 cm. H2O/ml., p less than 0.001) and bladder weights (225.2 +/- 21.4 mg. vs. 112.2 +/- 18.0 mg., p less than 0.01). No differences were noted in: 1) the thresholds or conduction velocities of axons in the bladder postganglionic nerves, 2) transmission in the major ganglion or 3) the latencies for firing in the supraspinal parasympathetic reflex pathway to the bladder. However, the supraspinal reflex, which was facilitated by bladder distension in 38% of control rats, was not facilitated in any diabetic rats. Another apparent difference in diabetic rats was the absence of spinal reflex response which was noted in 38% of control animals. This study confirmed that CMG changes in STZ-induced diabetic rats are similar to those observed clinically in patients with diabetic autonomic neuropathy, and in addition raise the possibility that these changes are produced by a defect in autonomic reflexes. It is also clear that alterations of the micturition reflex pathway in diabetic rats are distinct from those associated with another type of enlarged, abnormal bladder induced by bladder outlet obstruction.     

Transcutaneous assessment of renal function in conscious rats with a device for measuring FITC-sinistrin disappearance curves

Determination of the urinary or plasma clearance of exogenous renal markers, such as inulin or iohexol, is considered to be the gold standard for glomerular filtration rate (GFR) measurement. Here, we describe a technique allowing determination of renal function based on transcutaneously measured elimination kinetics of fluorescein isothiocyanate (FITC)-sinistrin, the FITC-labeled active pharmaceutical ingredient of a commercially available marker of GFR. A low cost device transcutaneously excites FITC-sinistrin at 480 nm and detects the emitted light through the skin at 520 nm. A radio-frequency transmission allows remote monitoring and real-time analysis of FITC-sinistrin excretion as a marker of renal function. Due to miniaturization, the whole device fits on the back of freely moving rats, and requires neither blood sampling nor laboratory assays. As proof of principle, comparative measurements of transcutaneous and plasma elimination kinetics of FITC-sinistrin were compared in freely moving healthy rats, rats showing reduced kidney function due to unilateral nephrectomy and PKD/Mhm rats with cystic kidney disease. Results show highly comparable elimination half-lives and GFR values in all animal groups. Bland-Altman analysis of enzymatically compared with transcutaneously measured GFR found a mean difference (bias) of 0.01 and a -0.30 to 0.33?ml/min per 100?g body weight with 95% limit of agreement. Thus, with this device, renal function can be reliably measured in freely moving rats eliminating the need for and influence of anesthesia on renal function.     

大鼠膀胱癌模型的光动力学治疗

目的　验证采用新型光敏剂的光动力学治疗方法对于SD大鼠膀胱癌动物模型的有效性。方法　使用 0 .0 5 %N 丁基 N(4 羟丁基 )亚硝胺 (BBN)诱导成功的SD大鼠随机分为试验组2 0只和对照组 7只。实验组大鼠用剂量为 50mg/kg体重光敏剂溶液灌胃 ,2 4h后打开膀胱进行激光照射 ,能量为 50J/cm2 ,72h后取肿瘤标本送病理分析和DNA含量测定 ,对照组术前不灌药物。结果　光动力学治疗法 (PDT)治疗后试验组的肿瘤坏死发生率和面积均高于对照组 ,差异有显著性 (P <0 .0 5)。样本的平均DNA质量均数 :实验组 9.50 5pg,对照组 1 4 .2 69pg,差异有显著性 (P<0 .0 5)。结论　以CDHS80 1作为光敏剂的光动力学治疗对于SD大鼠膀胱癌模型是有效的     

Detection of urinary incontinence during ambulatory monitoring of bladder function by a temperature-sensitive device

Objectives To determine whether the difference between urinary and perineal temperatures is sufficient to allow registration of incontinent episodes by detection of temperature change alone. To design and assess the use of a diode-based temperature-sensitive device in the detection of episodes of urinary incontinence in long-term ambulatory monitoring (LTAM) studies. Subjects and methods Perineal temperature recordings were made in 46 women during various activities. A temperature-sensitive device consisting of six IN4148 diodes, spanning 5 cm, and a nearby reference negative diode, was placed in a light perineal pad and attached to a portable amplifier/digitizer and recorder. The performance of the device was determined by comparison with increases in pad weight in 51 incontinent and 23 continent control subjects. Results A sufficient temperature differential existed between perineal and urinary temperature during all activities except being seated with crossed legs. Incontinence was reliably detected by the temperature-sensitive device. The device had a sensitivity of 95.2% and a specificity of 90.6% compared to a pad test. Conclusions This temperature-sensitive device offers a new method for detecting urinary incontinence during LTAM studies. It can be fitted in an unobtrusive perineal pad and has a higher sensitivity and specificity for the detection of incontinence when compared to a pad test. It may also be used as a marker of voiding in ambulatory studies not employing an integrated voiding channel.