Anionic and cationic drug secretion in the isolated perfused rat kidney after neonatal surgical induction of ureteric obstruction

OBJECTIVE: To study the pathophysiological changes of renal tubular drug transport mechanisms in congenital renal obstruction, by developing a model for perfusing the isolated kidney (IPK) after neonatal surgical induction of partial ureteric obstruction in Hanover Wistar rats. MATERIAL AND METHODS: Moderately severe obstruction of the right kidney of male rats was created by burying a segment of the right ureter under the psoas fascia at 5-7 days after birth. Different fluorescent substrates for renal organic anion and cation drug transport systems were added to the IPK, and the concentration of these substances with time analysed in perfusate and urine. RESULTS: The reproducibility in all groups of the glomerular filtration rate (GFR) and drug excretion was remarkably good. GFR was significantly lower in obstructed kidneys than in unobstructed kidneys. 123Rhodamine, a marker for organic cation and P-glycoprotein transport, had a significantly lower maximum excretion rate in the obstructed than in unobstructed kidneys. Renal fractional clearance (123rhodamine clearance corrected for diminished GFR) was also significantly lower in obstructed kidneys. There was no significant difference in maximum excretion (absolute and corrected GFR) for Lucifer Yellow, a marker for sodium-dependent organic anion transport. The maximum excretion rate of calcein, a marker for sodium-independent organic anion transport, was significantly lower in the obstructed than in the unobstructed kidneys, but significantly higher after correcting for reduced GFR. CONCLUSION: The IPK is a good model for studying the effect of neonatal renal obstruction on tubular drug transport. These results show that organic anion and cation transport mechanisms are affected differently by obstruction.     

Recoverability of renal functions after relief of partial ureteric obstruction of solitary kidney: impact of ferulic acid

What's known on the subject? and What does the study add? It is known that the kidney damage continues even after release of ureteric obstruction. This study found that giving ferulic acid, antioxidant, after release of ureteric obstruction enhanced the recovery of kidney functions in solitary kidney.

OBJECTIVE

• ? To evaluate the effect of ferulic acid (FA) on the recovery of renal function and renal damage after relief of partial ureteric obstruction (PUO) of a solitary kidney.

METHODS

• ? Male mongrel dogs (n= 32) were classified into three groups: sham (eight), control (12) and study (12).
• ? A right nephrectomy was carried out and dogs in the study and control groups were subjected to 4 weeks of PUO.
• ? Serum creatinine, creatinine clearance (CrCl) and renographic clearance (RC) were measured at baseline, after 4 weeks of obstruction and 8 weeks after relief of obstruction.
• ? Markers of lipid peroxidation (malondialdehyde [MDA]), superoxide dismutase (SOD), and reduced glutathione (GSH), and immunostaining of markers of apoptosis (caspase 3 and Bcl2), cell proliferation (Ki67) and interstitial fibrosis in the kidney were evaluated at the end of experiment.

RESULTS

• ? Ferulic acid enhanced the recovery of serum creatinine, CrCl and RC by an extra 22%, 26% and 33.7%, respectively, of the basal values at 8 weeks, after relief of 4 weeks' obstruction.
• ? In addition, FA caused a significant decrease in MDA and a significant increase in GSH and SOD.
• ? Ferulic acid also significantly reduced the interstitial fibrosis, and caspase 3 expression, and significantly increased the expression of Bcl2 and Ki67 in kidney tissues at 8 weeks after relief of the obstruction.

CONCLUSION

• ? Ferulic acid enhances the recoverability of renal function and minimizes the renal damage through reduction of oxidative stress, tubular apoptosis and the interstitial fibrosis in the solitary kidney after relief of PUO.

     

Renal haemodynamics and prostaglandin synthesis in partial unilateral ureteric obstruction

Haemodynamic changes in partial unilateral ureteric obstruction (PUUO) may be related to altered prostaglandin synthesis. In 12 dogs the left ureter was partially obstructed for 5 weeks. In six dogs the ureter was reimplanted into the bladder and to investigate the effect of this procedure on the contralateral side the other six animals underwent ipsilateral nephroureterectomy. Renal blood flow (RBF) was measured by the distribution of radiolabelled microspheres. Changes in urinary prostaglandin (PG) concentrations were validated by renin activity using angiotensin I. Reduced left RBF during obstruction was associated with increased thromboxane A₂ synthesis (P<0.01). Increased RBF to the nonobstructed side was associated with elevated PGE₂ formation (P<0.05). Elevated angiotensin I levels (P<0.01) corresponded to maximal increases in PG synthesis. Reimplantation of the obstructed kidney did not exert a direct effect on contralateral RBF or PG concentration. Haemodynamic changes in PUUO in vivo are associated with alterations in renal PGs.     

Delayed proximal ureteric stricture formation after complex partial nephrectomy

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? As the indications for nephron sparing surgery continue to evolve, so do the potential complications. This study examines a rare but likely underreported complication of nephron sparing surgery in order to better counsel and treat patients with complex renal tumours.

OBJECTIVE

• ? To report and review our incidence of delayed ureteric stricture (US) after complex nephron‐sparing surgery (NSS).

PATIENTS AND METHODS

• ? Using our institutional kidney cancer database, we identified 720 patients who underwent NSS from 1 January 2000 until 31 December 2010 and identified eleven (1.5%) patients with a delayed US.
• ? Patient and tumour characteristics were reviewed.

RESULTS

• ? Median (range) tumour size and RENAL nephrometry score was 4.1 (2–7.2) cm and 10p (4–11p), respectively.
• ? There were eight of 10 solitary tumours (80%) located in the lower or mid‐pole of the kidney.
• ? There were eight of 11 patients with delayed US (72.7%) who experienced a postoperative urinary leak.
• ? There were two of 11 (18.2%) patients who experienced a postoperative retroperitoneal haemorrhage, with one of these patients requiring selective embolization.
• ? All US were in the upper third of the ureter and were diagnosed at a minimum of 10 weeks postoperatively (median 154 days, range 70–400 days).

CONCLUSIONS

• ? US formation is an uncommon and under‐reported event after complex NSS.
• ? Risk factors appear to include tumour complexity, imperative indications, mid‐ or lower pole location, postoperative urinary leak and haemorrhage.
• ? Although uncommon, postoperative US can occur after NSS for complex renal masses, necessitating patient counselling and diligent postoperative surveillance.

     

Current status of metal stents for managing malignant ureteric obstruction

Obstruction of the ureters caused by extrinsic compression from a primary tumour or retroperitoneal lymph node masses is not unusual in the course of advanced pelvic malignancies. Most of the cases are of gynaecological or gastrointestinal origin, and the situation can be aggravated by peri‐ureteric fibrosis, a long‐term adverse event of previous chemotherapy or radiotherapy. Undoubtedly upper urinary tract decompression and maintenance of ureteric patency, even as a palliative measure, is important in managing these patients. Options for upper tract decompression include percutaneous nephrostomy, retrograde stenting and open urinary diversion. Plastic stents have long been used for managing malignant ureteric obstruction, but their overall success remains limited. Plastic stents often fail to be placed correctly, require regular exchange, and are faced with a high incidence of encrustation and migration. For these reasons plastic stents have been unsuccessful for long‐term maintenance of ureteric patency. To overcome these limitations metal stents were introduced and recently developed in an effort to ensure better long‐term patency of the obstructed ureter, fewer hospital admissions for stent change and better overall quality of life. In the present review the clinical applications of different types of metal stents are discussed, with a specific focus on the latest advances and the future options for managing malignant ureteric obstruction.     

Prognostic factors in malignant ureteric obstruction

OBJECTIVE

To validate a model to stratify patients with obstructive nephropathy due to malignant ureteric obstruction, associated with a poor prognosis, into different prognostic groups, as a recent report identified low serum albumin, degree of hydronephrosis and number of events related to metastatic disease as prognostic indicators before palliative decompression.

PATIENTS AND METHODS

We retrospectively review the charts to identify all patients who had a nephrostomy tube inserted for malignant ureteric obstruction. Laboratory and clinical factors that might influence prognosis were reviewed to attempt to externally validate the previously identified factors and model for risk stratification.

RESULTS

The median (range) age of the 49 patients identified was 71 (36–91) years, and the median survival was 174 (14–602) days. Tumours were of urological origin in 66% of patients. Patients with prostate cancer had nephrostomy tubes indwelling for a mean of 279 days, vs 190 days (P = 0.07) for patients with tumours not of prostatic origin. A serum albumin level of >30 g/L (P ≤ 0.001), serum sodium <135 mmol/L (P = 0.019) and three or more events related to dissemination of cancer (P = 0.04) were factors associated with a significantly shorter mean survival. Complications related to the nephrostomy tube were experienced by 39% of patients. The model proved useful in stratifying these patients into different risk groups (P = 0.002).

CONCLUSION

Consistent with a previous report we showed that a low serum albumin level and events related to metastatic disease were indicative of a poor prognosis. We also found that a low serum sodium level might be associated with a worse prognosis. We externally validated a model for stratifying patients into different prognostic groups. Palliative decompression is associated with significant morbidity.     

Protein kinase C inhibitor prevents renal apoptotic and fibrotic changes in response to partial ureteric obstruction

What's known on the subject? and What does the study add? Protein kinase C inhibitor (PKCI) can decrease glomerular and tubular cell apoptosis and mitosis and attenuate collagen accumulation and fibronectin expression in a PUUO rat model. Although the role of PKC has been well studied in diabetic nephropathy, there is no report on its role in obstructive nephropathy. This investigation evaluated the processes that were associated with the activation of PKCα and PKCβ pathways and showed that PKCI played an important role in the protection of renal function during ureteric obstruction.

OBJECTIVES

• ? To investigate the expression of the protein kinase C (PKC) pathway after partial unilateral ureteric obstruction (PUUO).
• ? To evaluate the therapeutic potential of a PKC inhibitor (PKCI) in obstructive nephropathy.

MATERIALS AND METHODS

• ? Thirty‐six rats were divided into three groups. One sham‐operated group served as the control. The other two groups received PUUO surgery, after which one group received no treatment and the other group was treated with PKCI, chelerythrine.
• ? The severity of hydronephrosis and renal morphology were assessed: tubular and glomerularcell apoptosis, mitosis and interstitial fibrosis were examined using immunohistochemistry.
• ? Western immunoblots were performed to determine fibronectin, transforming growth factor‐β (TGF‐β), and PKC isoform levels.

RESULTS

• ? Two weeks after PUUO surgery, hydronephrosis progressively developed. Tubular‐interstitial fibrosis, collagen deposition and fibronectin expression were increased.
• ? PUUO also activated the expression of PKCα and PKCβ and the translocation of PKCs from cell cytosol to cell membranes.
• ? Treatment with PKCI significantly decreased PKCα and PKCβ expression and translocation in the renal cortex.
• ? Treatment with PKCI also reduced the severity of hydronephrosis, decreased both glomerular and tubular cell apoptosis and mitosis, and attenuated the collagen and fibronectin accumulation in renal interstitium.

CONCLUSIONS

• ? Renal tubular apoptosis and interstitial fibrosis after obstructive nephropathy are associated with PKCα and PKCβ activation.
• ? The PKCI, chelerythrine, is capable of decreasing PKC expression and translocation in the renal cortex, suggesting that this inhibitor may have therapeutic potential in the protection of renal function in the first few weeks after PUUO surgery.

     

Stent-related ureteric obstruction in paediatric renal transplantation

The rates of ureteric obstruction and complications for use of externally draining uretero-vesico-cutaneous (external) stents (Group 1: n=39) and the use of internal uretero-vesical (double-J) stents (Group 2: n=16), in 55 of 64 consecutive paediatric renal-transplant recipients, performed at our institution between January 1996 and December 2003, have been compared. Serum creatinine levels pre and post-operatively and pre and post-stent removal were recorded. The diagnosis of ureteric obstruction was based on an increase in serum creatinine of 20%, in conjunction with ultrasound evidence of hydronephrosis or hydroureter, where other causes of renal dysfunction were excluded. Ureteric obstruction occurred in 13 of the 39 patients (33.3%) in Group 1, compared with only one case of ureteric obstruction in the 16 patients (6.25%) in Group 2 (OR=7.5, 95% CI=0.8–70, P=0.038). There was no evidence of a difference in the number of urinary tract infections (9/39 in Group 1, 6/16 in Group 2, OR=0.5, 95% CI=0.14 to 1.8, P=0.275) or the mean length of hospital stay (10.9 days in Group 1, 10.1 days in Group 2, 95% CI=–2.3 to 4 days, P=0.565) between the two groups. Glomerular filtration rate (GFR) improved in the week after stent removal in Group 2, but deteriorated in Group 1 (P=0.07). This non-randomised comparison of stent types supports the use of prophylactic double-J stents in paediatric renal transplantation- in terms of decreased ureteric complications and improved renal function post-stent removal.This work was presented in abstract/oral poster form at The Thirteenth Congress of the International Pediatric Nephrology Association in Adelaide, Australia, in August 2004     

Alfuzosin attenuates erectile dysfunction in rats with partial bladder outlet obstruction

OBJECTIVE

To determine how partial bladder outlet obstruction (PBOO) in a rat model affects erectile function, and whether an uroselective α1‐adrenoceptor antagonist, alfuzosin (Sanofi‐Aventis, Paris, France) attenuates any erectile dysfunction (ED).

MATERIALS AND METHODS

Adult male Sprague‐Dawley rats (120) were randomized into four groups: 1, sham‐operated; 2, alfuzosin‐treated; 3, PBOO; and 4, alfuzosin‐treated with PBOO. Groups 3 and 4 were subjected to PBOO for 6 weeks by ligation of the urethra, while groups 2 and 4 rats received daily oral alfuzosin (10 mg/day) for 6 weeks. In vivo erectile responses were monitored by evaluating ratios of intracavernosal pressure (ICP)/mean arterial pressure, and total ICP (area under the curve). Organ‐bath studies were performed on corpus cavernosum smooth muscle (CCSM) strips. Nitric oxide synthase (NOS) expression was determined immunohistochemically (IHC) for neuronal (n)NOS and by Western blot analysis for endothelial (e) and inducible (i) NOS protein.

RESULTS

Rats with PBOO showed lower erectile responses than controls. Maximum electrical field stimulation‐mediated and endothelium‐dependent acetylcholine‐induced relaxations and contractile responses to phenylephrine were significantly reduced in CCSM strips from the PBOO group. The NO donor sodium nitroprusside completely relaxed CCSM from rats in all groups. IHC analyses showed decreased expression of nNOS in PBOO groups compared with controls; by contrast, protein expression of eNOS and iNOS was increased. Alfuzosin‐treatment partially attenuated functional and molecular changes in penises of PBOO rats.

CONCLUSION

Rats with PBOO show ED, most likely due to altered NOS expression and NO bioavailability. The α‐adrenoreceptor antagonist alfuzosin reversed this ED by altering sympathetic tone, increasing NO‐induced relaxation and augmenting blood flow in the penis. This study suggests a rationale for further clinical trials using combinations of α‐adrenoceptor antagonists and phosphodiesterase‐5 inhibitors in patients with ED and lower urinary tract symptoms.     

The effect of partial unilateral ureteral obstruction release and allopurinol on the renal malondialdehyde and glutathione levels

PURPOSE: The aim of the present study was to evaluate whether relief of partial unilateral ureteral obstruction (PUUO) with or without antioxidant drug affect renal tissue malonedialdehyde (MDA) and glutathion (GSH) levels. MATERIALS AND METHODS: A total of 25 rats were used in this PUUO study. Partial unilateral ureteral obstruction was created by the burial of the upper one-third of the left ureter in the psoas muscle. The rats were sacrificed on 28th day following PUUO. Relief of the obstruction was performed twenty minutes before sacrifice by cutting the proximal ureter in reperfusion group. 50 mg/kg intraperitoneal allopurinol was administered 20 minutes before relief of obstruction in the antioxidant group. Renal tissue MDA and GSH levels were measured in both kidneys. RESULTS: At the end of the study 5, 7 and 7 rats could only be interpreted in sham, reperfusion and antioxidant groups, respectively. While the mean left and right renal MDA and GSH levels were statistically different from each other in reperfusion group (P < 0.001), there were no significant differences in the sham (P > 0.05) and antioxidant (P > 0.05) group. Both the mean sham group left and right renal tissue MDA or GSH levels were significantly different from reperfusion group, but only the mean sham group left renal tissue MDA and right renal tissue GSH levels were not statistically different from antioxidant group (P < 0.05). The mean left or right renal MDA and GSH tissue levels of the antioxidant group were statistically different from reperfusion group (P < 0.05) except for the right renal tissue GSH level (P > 0.05). CONCLUSION: Partial unilateral ureteral obstruction leads to oxidative injury by relief of obstruction in both kidneys. The antioxidant allopurinol has a beneficial effect on renal MDA and GSH levels in both kidneys.     

多层螺旋CT在输尿管结核性梗阻诊断中的应用

目的探讨多层螺旋CT(MSCT)在输尿管结核性梗阻诊断中的作用。方法对2例IVU检查发现肾积水输尿管不显影及RGP插管受阻的患者行MSCT扫描，并行3D重建，将诊断结果与手术结果对照。结果MSCT能明确输尿管梗阻的部位和性质。手术结果证实MSCT诊断正确。结论MSCT能对输尿管结核梗阻作出明确诊断，是一种有效的无创检查手段。     

Relative renal function does not improve after relieving chronic renal obstruction

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Technetium‐99m MAG3 renography can be used to quantify relative renal function (RRF). Deterioration of renal function occurs with chronic obstruction. Small studies have previously shown that RRF is not improved in adult patients after pyeloplasty. Some studies have suggested that patients with higher preoperative RRF are more likely to improve. To our knowledge, these data represent the largest review of cases related to this subject. This study verifies past studies' assertions that RRF does not improve after relief of chronic renal obstruction. Using multivariable analysis, we identify lower age and lower preoperative RRF as predictors of >7% improvement in RRF. These data suggest that the aim of relieving obstruction should be to maintain RRF and alleviate symptoms, but not to seek improvement in overall renal function.

OBJECTIVE

• ? To determine the change in relative renal function (RRF) after relief of chronic obstruction in adults.

PATIENTS AND METHODS

• ? We retrospectively identified 85 adult patients who underwent scintigraphic diuretic renography before and after an intervention to relieve chronic unilateral renal obstruction.
• ? Patients were stratified into groups of low (<20%), medium (20‐40%) and high (>40%) preoperative RRF in the obstructed kidney. Each group was assessed for change in RRF after relief of obstruction.
• ? We performed multivariable logistic regression analysis to determine whether age and pre‐procedural RRF predicted a >7% improvement in RRF, controlling for medical comorbidities and type of obstruction.

RESULTS

• ? The mean (sd ) patient age was 43.6 (16.8) years and 66% of patients were female.
• ? The mean (sd ) pre‐ and postoperative RRF values were not significantly different (37.6 [12.3] % vs 38.4 [13.6] %; P = 0.31).
• ? Patients stratified by low, medium and high preoperative function showed no significant change in postoperative RRF (P = 0.53, 0.39 and 0.77, respectively).
• ? In multivariable logistic regression analysis, younger age (odds ratio [OR] 0.90, 95% confidence interval [CI] 0.83–0.98) and lower preoperative RRF (OR 0.90, 95% CI 0.83–0.97) predicted improvement in RRF of >7%, after adjustment.

CONCLUSIONS

• ? RRF does not significantly increase after relief of chronic obstruction.
• ? The goals of relieving chronic renal obstruction should be to maintain renal function and relieve symptoms, but not to regain renal function.

     

膀胱出口部分梗阻大鼠膀胱超微结构和尿流动力学的关系

目的观察大鼠膀胱出口部分梗阻(PBOO)后尿流动力学及超微结构变化,探讨膀胱出口部分梗阻后超微结构和尿流动力学改变的关系。方法 48只雌性Sprague-Dawley大鼠随机分为假手术组(Sham组)24只、PBOO 2周组8只、4周组8只、8周组8只。饲养后,于相应周数解剖膀胱,测定膀胱重量、不稳定收缩发生率、容量、漏尿点压及膀胱顺应性,观察逼尿肌超微结构改变等指标。结果 PBOO 2周、4周、8周膀胱重量分别为(220±24.2)mg、(327.8±27.7)mg、(521.6±24.7)mg,Sham组为(108.5±6.3)mg(P0.05);不稳定收缩发生率分别为50%(4/8)、87.5%(7/8)、37.5%(3/8),Sham组0%为(0/24)(P0.05);膀胱最大容积分别为(0.65±0.26)mL、(1.57±0.70)mL、(5.62±1.39)mL,Sham组为(0.30±0.08)mL(P0.05)。梗阻组漏尿点压为2周组(31.5±4.78)cmH2O、4周组(56.5±7.46)cmH2O、8周组(33.00±9.92)cmH2O,Sham组(22.13±3.18)cmH2O(P0.05)。膀胱顺应性PBOO 2周组、4周组与Sham组比较,差异无统计学意义(P0.05),8周组与Sham组相比,差异有统计学意义(P0.05)。透射电镜观察结果为大鼠PBOO后线粒体增多、水肿,细胞膜穴样凹陷增多,中间连接减少、缝隙连接及胞突连接增多。结论膀胱出口部分梗阻后由代偿期进入失代偿期,可以通过尿流动力学进行检测,而产生这一系列变化的形态学基础可能是超微结构的改变。     

Optimal management of distal ureteric strictures following renal transplantation: a systematic review

Our objective was to define optimal management of distal ureteric strictures following renal transplantation. A systematic review on PubMed identified 34 articles (385 patients). Primary endpoints were success rates and complications of specific primary and secondary treatments (following failure of primary treatment). Among primary treatments (n = 303), the open approach had 85.4% success (95% CI 72.5–93.1) and the endourological approach had 64.3% success (95% CI 58.3–69.9). Among secondary treatments (n = 82), the open approach had 93.1% success (95% CI 77.0–99.2) and the endourological approach had 75.5% success (95% CI 62.3–85.2). The most common primary open treatment was ureteric reimplantation (n = 33, 81.8% success, 95% CI 65.2–91.8). The most common primary endourological treatment was dilation (n = 133, 58.6% success, 95% CI 50.1–66.7). Fourteen complications, including death (4 weeks post‐op) and graft loss (12 days post‐op), followed endourological treatment. One complication followed open treatment. This is the first systematic review to examine the success rates and complications of specific treatments for distal ureteric strictures following renal transplantation. Our review indicates that open management has higher success rates and fewer complications than endourological management as a primary and secondary treatment for post‐transplant distal ureteric strictures. We also outline a post‐transplant ureteric stricture evaluation and treatment algorithm.     

3H-thymidine uptake by the rat urinary bladder after partial outflow obstruction

Partial outflow obstruction induces marked changes in detrusor contractile function and morphology. One common finding in all experimental animal models of outflow obstruction is a significant increase in bladder mass. It is not clear which tissue compartments undergo hypertrophy, hyperplasia, or both. The present study was designed to evaluate the time-related changes in ³H-thymidine uptake and distribution within each tissue compartment induced by partial outflow obstruction using autoradiography. Partial outlet obstruction in rats induced a mild 2-fold increase in mass over a 14 day period. DNA synthesis increased significantly at 1 day following surgery, and remained increased through 7 days. DNA synthesis returned to control levels by 14 days. Distribution studies (using autoradiography) demonstrated a marked increase in the number of labelled urothelium cells at 1 and 3 days after obstruction. Sham surgery also initiated an increase in the number of labelled cells in the urothelium at 1 day. Although both sham and obstructive surgeries induced substantial increases in the labelling of cells within the connective tissue components, the magnitude of the increase in labelled connective tissue cells of the obstructed bladders was greater than that of the sham group. The number of labelled smooth muscle cells of the obstructed bladder increased significantly at 3, 5, and 7 days. However, there were no changes in smooth muscle incorporation of ³H-thymidine by the sham groups. In conclusion, partial outflow obstruction induced time-dependent increases in bladder wall proliferation. The urothelium and connective tissue were the compartments first affected, followed by smooth muscle. © 1994 Wiley-Liss, Inc.     

Segmental multicystic dysplasia and ureteropelvic junction obstruction in a nonduplicated kidney

A 2-month-old child presented for evaluation of prenatal hydronephrosis. Imaging studies were consistent with a right duplex system with a dysplastic, nonfunctioning upper pole and lower pole ureteropelvic junction obstruction. We proceeded with removal of the upper pole and pyeloplasty and were surprised to find a single collecting system with a cystic, dysplastic upper pole segment and the absence of an upper pole pelvis or ureter. The rare diagnosis of a segmental multicystic dysplastic kidney with ipsilateral ureteropelvic junction obstruction was made. We present a review of the case and of previous literature on this topic.     

Effect of partial outflow obstruction on rat detrusor contractility and intracellular free calcium concentration

Partial outlet obstruction induces significant alteration in detrusor contractility. A mild obstruction can result in increased contractile force, whereas severe obstruction results in marked contractile dysfunction. The cellular mechanisms mediating these alterations in the contractile response are presently not known. In the current study, we have investigated the effect of both mild and severe partial outlet obstruction on detrusor contractility and correlated the contractile response to field stimulation, bethanechol, adenosine triphosphate (ATP), and KCl with the level of intracellular free calcium using FURA-2 fluorescence. Our results are as follows. Severe obstruction induced a significantly greater increase in bladder weight than mild obstruction. In general, mild outlet obstruction induced an increase in the contractile responses to field stimulation, bethanechol, ATP, and KCl, whereas severe outlet obstruction induced a decrease to field stimulation and ATP. In general, the stimulated increase in intracellular free calcium paralleled the contractile response. The results indicate that the alterations in the contractile response to field stimulation and pharmacological stimulation induced by partial outlet obstruction may be mediated by altered calcium translocation and intracellular release. © 1994 Wiley-Liss, Inc.     

可复性单侧输尿管部分梗阻动物模型的建立

目的探索建立一种较为理想的、可复性强的输尿管部分梗阻的动物模型。方法选用雄性Wistar大鼠48只,应用输尿管对侧腰大肌悬吊术建立输尿管部分梗阻模型,分别于6个不同时相即造模后1、2、4、6、8周（解除梗阻后4周）、10周（解除梗阻后4周）各取8只动物,同位素肾动态扫描检测造模后不同时相梗阻肾功能受损情况、梗阻解除后肾功能恢复情况,光镜下观察不同梗阻时段肾脏病理改变。结果造模后2周成模,成模率为97.9%。肾动态显像：与梗阻前比较,梗阻肾肾小球滤过率明显降低（P〈0.05）。梗阻后4周解除梗阻,肾功能明显恢复;6周解除梗阻,肾功能不能恢复至正常。结论输尿管对侧腰大肌悬吊术是较为理想的输尿管部分梗阻模型,该方法成模率高,梗阻具有可逆性。