Diabetes slows the recovery from urinary incontinence due to simulated childbirth in female rats

This study was done to test the hypothesis that simulated vaginal birth by vaginal distension (VD) causes more severe urinary incontinence and slower recovery in diabetic rats. After measuring baseline leak point pressure (LPP) in 16 diabetes mellitus (DM) and 16 age- and weight-matched control (Ct) female Sprague-Dawley rats, these animals underwent either VD or sham VD (sham). Four and ten days after the procedures, LPP and conscious cystometry were assessed. Tissues were then harvested and examined by light microscopy. LPP at baseline was equal among all four groups. Four days after VD, LPP in both VD groups dropped to significantly lower levels than in sham rats (P < 0.001). Moreover, LPP in the DM+VD group was significantly lower than in the Ct+VD group. At 10 days, LPP in the Ct+VD group had recovered to its baseline value, whereas the LPP in the DM+VD group remained significantly reduced. DM rats had larger bladder capacity and longer voiding intervals than Ct rats. Histological findings included more severe damage to the external sphincter striated musculature of the urethra in DM+VD group compared with Ct+VD. In conclusion, these findings suggest that DM causes increased severity and delayed functional recovery from the effects of simulated childbirth.     

Long term effects of muscle-derived stem cells on leak point pressure and closing pressure in rats with transected pudendal nerves

The survival of muscle-derived cells injected into the urethra and bladder wall was described recently. In this study, we tested whether injections of periurethral muscle-derived stem cells (MDSC) and bovine collagen (BC) after denervation of the pudendal nerve could increase leak point pressure (LPP) and closing pressure (CP) in female rats over the long term. S-D rats were anesthetized with halothane and the pudendal nerves transected bilaterally via a dorsal incision in order to denervate the external urethral sphincter. In the collagen and MDSC groups (C & M), injection of collagen or MDSC was made into the proximal urethra after pudendal nerve transection. At 4 and 12 week, visually identified LPP and CP measurements were made using the vertical tilt/intravesical pressure clamp model of stress urinary incontinence. The rats were then sacrificed and urethra harvested for histology. Both LPP and CP were significantly lower in the denervated (D) group at each time compared with the normal (N), C, and M groups, and both LPP and CP in the C and M groups were significantly higher than in the D group at both 4 and 12 weeks. The persistence of MDSC over the period of study was verified by histology. Thus pudendal nerve denervation led to a progressive decline in LPP and CP that was evident at 4 week and persisted to 12 week, and injection of MDSC into the denervated rats led to a long term increase in LPP and CP.     

压力性尿失禁动物模型尿道功能和盆底肌力的比较

目的:比较不同压力性尿失禁(stress urinary incontinence,SUI)动物模型在尿流动力学和盆底肌力方面的差异,以寻求最能模拟SUI的动物模型。方法:取64只大鼠随机均分为阴道扩张模型组(vaginal distension,VD)和阴部神经压榨模型组(pudendal nerve crush,PNC)和阴部神经切断模型组(pudendal nerve transection,PNT)以及VD+PNC造模组4组,每组16只,另取4只大鼠作为正常对照组。造模后第2天,所有大鼠行喷嚏试验。造模后第4天、第10天、3周、6周,测定尿流动力学和盆底肌力。正常对照组大鼠在喷嚏试验后进行尿流动力学和盆底肌力测定。结果:喷嚏实验结果显示正常对照组未观察到阳性大鼠(0/4),各模型组喷嚏试验结果阳性率均显著高于正常对照组(P0.05)。动力学检测显示:与正常组(40.3±3.4 cm H_2O)相比,VD组在造模后4d的LPP值显著降低(P0.05),而造模后10d、3周和6周时的LPP值无统计学差异(P0.05);PNC组和PNC+VD组在造模后4d、10d、3周时的LPP值均显著降低(P0.05),而在造模后6周时无统计学差异(P0.05);PNT组在造模后4d、10d、3周和6周时的LPP值均显著降低(P0.05)。最大膀胱容量测定显示:与正常组(2.42±0.12 mL)相比,VD组在造模后10d的MBC值显著降低(P0.05),而造模后4d、3周和6周时无统计学差异(P0.05);PNC组在造模后10d、3周时显著降低(P0.05),而在造模后4d和6周时无统计学差异(P0.05);PNC+VD组和PNT组在造模后10d及3周和6周时均显著降低(P0.05),而在造模后4d时无统计学差异(P0.05)。盆底肌力测定结果显示:与正常组的耻尾肌肌力值(2.71±0.12 g/g)相比,VD组在造模后10d显著降低(P0.05),而造模后4d、3周和6周时无统计学差异(P0.05);PNC组在造模后10d、3周时显著降低(P0.05),而在造模后4d和6周时无统计学差异(P0.05);PNC+VD组和PNT在造模后10d及3周和6周时均显著降低(P0.05),而在造模后4d时无统计学差异(P0.05)。结论:VD、PNC、VD+PNC和PNT造模均能有效模拟出SUI发病中的盆底神经和肌肉损伤。其中,VD造模主要引起盆底肌的直接损伤,但其恢复较快。PNC和PNT造模则能损伤阴部神经并间接地造成盆底肌的失神经性萎缩,但PNT所造成的损伤较难恢复,不能有效地模拟SUI的自然修复过程。而VD+PNC造模则兼具VD和PNC两种造模方法的特点,能从多个层面模拟SUI的发病。因此,在实践中应根据实验研究的层面采用合适的动物模型。     

Association of overactive bladder and stress urinary incontinence in rats with pudendal nerve ligation injury

Approximately one-third of patients with stress urinary incontinence (SUI) also suffer from urgency incontinence, which is one of the major symptoms of overactive bladder (OAB) syndrome. Pudendal nerve injury has been recognized as a possible cause for both SUI and OAB. Therefore, we investigated the effects of pudendal nerve ligation (PNL) on bladder function and urinary continence in female Sprague-Dawley rats. Conscious cystometry with or without capsaicin pretreatment (125 mg/kg sc), leak point pressures (LPPs), contractile responses of bladder muscle strips to carbachol or phenylephrine, and levels of nerve growth factor (NGF) protein and mRNA in the bladder were compared in sham and PNL rats 4 wk after the injury. Urinary frequency detected by a reduction in intercontraction intervals and voided volume was observed in PNL rats compared with sham rats, but it was not seen in PNL rats with capsaicin pretreatment that desensitizes C-fiber-afferent pathways. LPPs in PNL rats were significantly decreased compared with sham rats. The contractile responses of detrusor muscle strips to phenylephrine, but not to carbachol, were significantly increased in PNL rats. The levels of NGF protein and mRNA in the bladder of PNL rats were significantly increased compared with sham rats. These results suggest that pudendal nerve neuropathy induced by PNL may be one of the potential risk factors for OAB, as well as SUI. Somato-visceral cross sensitization between somatic (pudendal) and visceral (bladder) sensory pathways that increases NGF expression and alpha(1)-adrenoceptor-mediated contractility in the bladder may be involved in this pathophysiological mechanism.     

Mesenchymal stem cells can improve anal pressures after anal sphincter injury

Objective.Fecal incontinence reduces the quality of life of many women but has no long-term cure. Research on mesenchymal stem cell (MSC)-based therapies has shown promising results. The primary aim of this study was to evaluate functional recovery after treatment with MSCs in two animal models of anal sphincter injury.Methods.Seventy virgin female rats received a sphincterotomy (SP) to model episiotomy, a pudendal nerve crush (PNC) to model the nerve injuries of childbirth, a sham SP, or a sham PNC. Anal sphincter pressures and electromyography (EMG) were recorded after injury but before treatment and 10 days after injury. Twenty-four hours after injury, each animal received either 0.2 ml saline or 2 million MSCs labelled with green fluorescing protein (GFP) suspended in 0.2 ml saline, either intravenously (IV) into the tail vein or intramuscularly (IM) into the anal sphincter.Results.MSCs delivered IV after SP resulted in a significant increase in resting anal sphincter pressure and peak pressure, as well as anal sphincter EMG amplitude and frequency 10 days after injury. MSCs delivered IM after SP resulted in a significant increase in resting anal sphincter pressure and anal sphincter EMG frequency but not amplitude. There was no improvement in anal sphincter pressure or EMG with in animals receiving MSCs after PNC. GFP-labelled cells were not found near the external anal sphincter in MSC-treated animals after SP.Conclusion.MSC treatment resulted in significant improvement in anal pressures after SP but not after PNC, suggesting that MSCs could be utilized to facilitate recovery after anal sphincter injury.     

老年男性脑卒中患者排尿功能障碍的尿动力学评估

目的:存在阻塞性尿路疾患的老年男性在发生脑血管意外后,是否可通过早期症状或排尿症状类型(梗阻性还是刺激性)来预判排尿功能障碍的病因。方法:选择57例脑卒中后主诉排尿障碍的老年男性患者,所有患者均有继发于良性前列腺增生(BPH)的膀胱出口梗阻(BOO)症状。采集病史并行体检,57位患者均实行尿动力学检查,检查结果行A-G图分析并分类为:有梗阻,无梗阻及可疑梗阻。结果:患者平均年龄70岁(54-87),按排尿障碍的主诉类型分组(纯刺激症状42%,纯梗阻症状34%,两者混合24%),其中51例(89%)在脑卒中发生后即出现排尿症状,47(82%)例患者出现逼尿肌反射亢进(DH),在三组患者中无显著统计学差异。压力流率分析显示,36(63%)位患者有出口梗阻,无梗阻14(24%)例,可疑梗阻7(13%)例。在3组患者中亦无显著统计学差异。结论:所有老年男性患者呈现的症状不能预测膀胱出口梗阻或逼尿肌反射亢进的尿动力学结果。中风发生后排尿功能障碍症状的发生率明显升高,表明由脑血管意外引起的排尿功能障碍合并前期具有膀胱出口梗阻疾病时,可能会使后者的症状恶化,反之亦然。     

Effect of aging on the response of biochemical markers in the rabbit subjected to short-term partial bladder obstruction

Purpose Partial bladder outlet obstruction (PBOO) results in marked biochemical alterations in the bladder. In this study, we focused on comparison of thapsigargin sensitive sarco/endoplasmic reticulum Ca²⁺ ATPase activity (SERCA) and Citrate Synthase after short term PBOO in young versus old rabbits. Materials and methods A total of 20 young and 20 mature male rabbits were divided into 4 sub-groups of 5 rabbits each (4 obstructed and 1 sham-control rabbit). The rabbits in the groups were evaluated after 1, 3, 7, and 14 days of obstruction, respectively. The activities of SERCA and citrate synthase were examined as markers for sarcoplasmic reticular calcium storage and release and mitochondrial function, respectively. Results The SERCA activity of bladder body smooth muscle in the young animals increased at 7 and 14 days. For the old rabbits, the SERCA activity decreased significantly by 1 day and remained this level throughout the course of obstruction, and was significantly lower than young at all time periods. The citrate synthase activity in the young animals decreased over the 1–7 days, and then returned toward control level by 14 days following obstruction. In the old animals, citrate synthase activity of bladder body smooth muscle progressively decreased over the course of the study, and was significantly lower in the old than the young animals after 14 days obstructed. Conclusion The urinary bladders of the young rabbits have a considerable greater ability to adapt to PBOO than do those of the old rabbits. The deterioration of mitochondrial and SR function may be important mechanisms underlying geriatric voiding dysfunction.     

Role of pudendal afferents in voiding efficiency in the rat

The reciprocal activities of the bladder and external urethral sphincter (EUS) are coordinated by descending projections from the pontine micturition center but are subjected to modulation by peripheral afferent inputs. Transection of the somatic pudendal nerve innervating the striated EUS decreases voiding efficiency and increases residual urine in the rat. The reduction in voiding efficiency was attributed to the lack of phasic bursting activity of the EUS following denervation. However, transection of the pudendal nerve also eliminates somatic sensory feedback that may play a role in voiding. We hypothesized that feedback from pudendal afferents is required for efficient voiding and that the loss of pudendal sensory activity contributes to the observed reduction in voiding efficiency following pudendal nerve transection. Quantitative cystometry in urethane anesthetized female rats following selective transection of pudendal nerve branches, following chemical modulation of urethral afferent activity, and following neuromuscular blockade revealed that pudendal nerve afferents contributed to efficient voiding. Sensory feedback augmented bladder contraction amplitude and duration, thereby increasing the driving force for urine expulsion. Second, sensory feedback was necessary to pattern appropriately the EUS activity into alternating bursts and quiescence during the bladder contraction. These findings demonstrate that the loss of pudendal sensory activity contributes to the reduction in voiding efficiency observed following pudendal nerve transection, and illustrate the importance of urethral sensory feedback in regulating bladder function.     

Influence of renal denervation on chronopharmacology of furosemide in rats.

Our previous studies have suggested that the adrenergic nervous system is involved in the mechanism responsible for the time-dependent change in the urinary excretion of furosemide in rats. To examine a potential role of renal nerves in this phenomenon, renal denervation or sham operation was performed using unilaterally nephrectomized rats. Furosemide (30 mg/kg) was given orally at 12 am or 12 pm. Urine was collected for 8 hours after furosemide dosing, and urinary excretions of furosemide and sodium were determined. Urinary furosemide excretion and diuretic effects of the agent (urine volume and urinary sodium) were significantly greater at 12 am than at 12 pm in the sham-operated group of rats. However these administration time-dependent changes in urinary furosemide and its diuretic effects disappeared in the renal-denervated group of animals. These results suggest that the renal nerves contribute to the time-dependent changes in the urinary excretion of furosemide and its subsequent diuretic effects.     

Effects of anesthesia on cystometry and leak point pressure of the female rat

Anesthetics operate by different mechanisms and are often used to perform urodynamics in animals. The objective of this study was to compare the effects of ketamine/xylazine and urethane anesthetics on filling, voiding, and leak point pressure (LPP) in female rats. Nineteen rats underwent awake cystometry 2 days after suprapubic bladder catheter implantation. Bladders were filled with saline (5 ml/hr), while bladder pressure was measured. Half the rats were then anesthetized with urethane i.p. and half were anesthetized with ketamine and xylazine i.p. (K/X). All rats then underwent cystometry and LPP testing under anesthesia. Spontaneous nonvoiding contractions were analyzed and capacity was determined by voiding or leakage. Capacity was significantly higher in awake rats (0.55 +/- 0.06 ml) than with either K/X (0.21 +/- 0.06 ml) or urethane (0.30 +/- 0.05 ml). The pressure just prior to voiding in awake cystometry (15.6 +/- 1.7 cm H2O) was not significantly different from that with either anesthetic (K/X: 10.1 +/- 1.0 cm H2O; urethane: 13.3 +/- 2.0 cm H2O). Spontaneous nonvoiding contractions occurred in 4 rats with urethane and 3 rats with K/X. The volume at which the first contraction occurred was significantly lower with K/X (0.05 +/- 0.02 ml) than urethane (0.19 +/- 0.04 ml). There was no significant difference in the frequency of spontaneous nonvoiding contractions between K/X (4.58 +/- 0.30/min) and urethane (5.16 +/- 2.66/min), nor was there a difference in LPP between anesthetics (K/X: 40.4 +/- 2.4 cm H2O; urethane: 36.2 +/- 3.9 cm H2O). The results suggest that urethane is preferable to K/X for anesthetized cystometry studies since it more closely simulates normal physiological responses.     

Ganglioside Treatment Modifies Abnormal Elemental Composition in Peripheral Nerve Myelinated Axons of Experimentally Diabetic Rats

Abstract: Effects of ganglioside administration on elemental composition of peripheral nerve myelinated axons and Schwann cells were determined in streptozotocin-induced diabetic rats and nondiabetic controls. Diabetic rats (50 days after administration of streptozocin) exhibited a loss of axoplasmic K and Cl concentrations in sciatic nerve relative to control, whereas intraaxonal levels of these elements increased in tibial nerve. These regional changes in diabetic rat constitute a reversal of the decreasing proximodistal gradients for K and Cl concentrations that characterize normal peripheral nerve. Treatment of diabetic rats with a ganglioside mixture for 30 days (initiated 20 days after the administration of streptozocin) returned proximal sciatic nerve axoplasmic K and Cl concentrations to control levels, whereas in tibial axons, concentrations of these elements increased further relative to diabetic levels. Also in the ganglioside/diabetic group, mean axoplasmic Na concentrations were reduced and Ca levels were elevated. Mixed ganglioside treatment of nondiabetic rats significantly increased axoplasmic dry weight concentrations of K and Cl in proximal sciatic and tibial axons. Schwann cells did not exhibit consistent alterations in elemental content regardless of treatment group. Changes in elemental composition evoked by ganglioside treatment of diabetic rats might reflect the ability of these substances to stimulate Na⁺,K⁺-ATPase activity and might be related to the mechanism by which gangliosides improve functional deficits in experimental diabetic neuropathy.     

Excitatory effects of bombesin receptors in urinary tract of normal and diabetic rats in vivo

Aims

Bombesin receptors (BB receptors) and bombesin related peptides are expressed in the lower urinary tract of rodents. Here we investigated whether in vivo activation of BB receptors can contract the urinary bladder and facilitate micturition in sham rats and in a diabetic rat model of voiding dysfunction.

Material and methods

In vivo cystometry experiments were performed in adult female Sprague–Dawley rats under urethane anesthesia. Diabetes was induced by streptozotocin (STZ; 65 mg/kg, i.p.) injection. Experiments were performed 9 and 20 weeks post STZ-treatment. Drugs included neuromedin B (NMB; BB1 receptor preferring agonist), and gastrin-releasing peptide (GRP; BB2 receptor preferring agonist).

Key findings

NMB and GRP (0.01–100 μg/kg in sham rats; 0.1–300 μg/kg in STZ-treated rats, i.v.) increased micturition frequency, bladder contraction amplitude and area under the curve dose dependently in both sham and STZ-treated rats. In addition, NMB (3, 10 μg/kg i.v.) triggered voiding in > 80% of STZ-treated rats when the bladder was filled to a sub-threshold voiding volume. NMB and GRP increased mean arterial pressure and heart rate at the highest doses, 100 and 300 μg/kg.

Significance

Activation of bombesin receptors facilitated neurogenic bladder contractions in vivo. Single applications of agonists enhanced or triggered voiding in sham rats as well as in the STZ-treated rat model of diabetic voiding dysfunction. These results suggest that BB receptors may be targeted for drug development for conditions associated with poor detrusor contraction such as an underactive bladder condition.     

Beneficial influence of fungal metabolite nigerloxin on eye lens abnormalities in experimental diabetes

Osmotic and oxidative stress have been implicated in the pathogenesis of diabetic cataract. Nigerloxin, a fungal metabolite, has been shown to possess aldose reductase inhibitory and free radical scavenging potential, in vitro. In the present study, the beneficial influence of nigerloxin was investigated on diabetes-induced alteration in the eye lens of rats treated with streptozotocin. Groups of diabetic rats were administered nigerloxin orally (100?mg·(kg body mass)(-1)·day(-1)) for 30?days. The activity of lens polyol pathway enzymes?(aldose reductase and sorbitol dehydrogenase), lipid peroxides, and advanced glycation end products (AGEs) were increased in the diabetic animals. Levels of glutathione as well as the activity of antioxidant enzymes?(superoxide dismutase, glutathione-S-transferase, and glutathione peroxidase) were decreased in the eye lens of the diabetic animals. The administration of nigerloxin significantly decreased levels of lipid peroxides and AGEs in the lens of the diabetic rats. Increase in the activity of aldose reductase and sorbitol dehydrogenase in the lens was countered by nigerloxin treatment. The activity of glutathione and antioxidant enzyme in the lens was significantly elevated in nigerloxin-treated diabetic rats. Examination of the treated rats' eyes indicated that nigerloxin delayed cataractogenesis in the diabetic rats. The results suggest the beneficial countering of polyol pathway enzymes and potentiation of the antioxidant defense system by nigerloxin in diabetic animals, implicating its potential in ameliorating cataracts in diabetics.     

Increased duration of simulated childbirth injuries results in increased time to recovery

Stress urinary incontinence (SUI) development is strongly correlated with vaginal childbirth, particularly increased duration of the second stage of labor. However, the mechanisms of pelvic floor injury leading to SUI are largely unknown. The aim of this study was to determine the effects of increased duration of vaginal distension (VD) on voiding cystometry, leak point pressure testing, and histology. Sixty-nine virgin female rats underwent VD with an inflated balloon for either 1 or 4 h, while 33 age-matched rats were sham-VD controls. Conscious cystometry, leak point pressure testing, and histopathology were determined 4 days, 10 days, and 6 wk after VD. The increase in abdominal pressure to leakage (LPP) during leak point pressure testing was significantly decreased in both distension groups 4 days after distension, indicative of short-term decreased urethral resistance. Ten days after VD, LPP was significantly decreased in the 4-h but not the 1-h distension group, indicating that a longer recovery time is needed after longer distension duration. Six weeks after VD, LPP was not significantly different from sham-VD values, indicating a return toward normal urethral resistance. In contrast, 6 wk after VD of either duration, the distended rats had not undergone the same increase in voided volume as the sham-VD group, suggesting that some effects of VD do not resolve within 6 wk. Both VD groups demonstrated histopathological evidence of acute injuries and tissue remodeling. In conclusion, this experiment suggests pressure-induced hypoxia as a possible mechanism of injury in vaginal delivery.     

Elevated urinary excretion of endothelins in streptozotocin diabetic rats

Endothelin-1,2 urinary excretion, has been determined in control and streptozotocin diabetic rats at different times after diabetes induction. Diabetic rats showed increased urinary excretion of endothelins as compared to control rats, already three days after diabetes induction and up to 20 weeks.     

Glomerular function in spontaneously diabetic rats.

This study was undertaken to determine whether hyperfiltration exists at the single nephron level and whether albumin excretion is increased early in the course of diabetes in Biobreeding rats. Diabetic rats were studied at 8-12 weeks after the onset of diabetes. Control animals were age-matched, diabetes-resistant rats. Urinary and tubular fluid albumin concentrations were measured by polyacrylamide gel electrophoresis. Clearance and micropuncture techniques were used to determine whole kidney and single nephron glomerular filtration rate, renal blood flow, and glomerular capillary pressure. The urinary albumin excretion rate (1.3 +/- 0.1 mg/24 hr) and the tubular fluid albumin concentration (4.7 +/- 0.7 mg/dl) in the diabetic group were significantly elevated when compared with urinary albumin excretion (0.9 +/- 0.1 mg/24 hr) and tubular fluid albumin concentration (2.5 +/- 0.5 mg/dl) in the control group. There were no significant differences in glomerular hemodynamics (whole kidney or single nephron glomerular filtration rate or glomerular capillary pressure) between diabetic and control rats. The kidney weight and kidney weight to body weight ratio were significantly higher in diabetic rats when compared with control rats. Early diabetes in Biobreeding rats is characterized by mild albuminuria and increased kidney size, but not glomerular hyperfiltration.     

Formononetin Ameliorates Diabetic Neuropathy by Increasing Expression of SIRT1 and NGF

Diabetic neuropathy is commonly observed complication in more than 50 % of type 2 diabetic patients. Histone deacetylases including SIRT1 have significant role to protect neuron from hyperglycemia induced damage. Formononetin (FMNT) is known for its effect to control hyperglycemia and also activate SIRT1. In present study, we evaluated effect of FMNT as SIRT1 activator in type 2 diabetic neuropathy. Type 2 diabetic neuropathy was induced in rats by modification of diet for 15 days using high fat diet and administration of streptozotocin (35 mg/kg/day, i. p.). FMNT treatment was initiated after confirmation of type 2 diabetes. Treatment was given for 16 weeks at 10, 20 and 40 mg/kg/day dose orally. FMNT treatment‐controlled hypoglycemia and reduced insulin resistance significantly in diabetic animals. FMNT treatment reduced oxidative stress in sciatic nerve tissue. FMNT treatment also reduced thermal hyperalgesia and mechanical allodynia significantly. It improved conduction velocity in nerve and unregulated SIRT1 and NGF expression in sciatic nerve tissue. Results of present study indicate that continuous administration of FMNT protected diabetic animals from hyperglycemia induced neuronal damage by controlling hyperglycemia and increasing SIRT1 and NGF expression in nerve tissue. Thus, FMNT can be an effective candidate for treatment of type 2 diabetic neuropathy.     

Influence of dietary capsaicin and onion on the metabolic abnormalities associated with streptozotocin induced diabetes mellitus

Effect of feeding 15 mg% capsaicin diet or 3% freeze dried onion powder containing diet were examined in albino rats rendered diabetic with streptozotocin injection. Diabetic rats maintained on onion diet for 8 weeks excreted comparatively less amounts of albumin, urea, creatinine and inorganic phosphorus. Dietary onion also partially reversed the abnormalities in plasma albumin, urea, creatinine and inorganic phosphorus in diabetic animals. Onion also produced a significant reduction in hyperglycemic status of diabetic animals. Diabetic rats maintained on onion diet had a lowered relative liver weight at the end of the study compared to diabetic control group. Diabetic rats fed onion diet also exhibited lowered lipid peroxides in circulation and in urine when compared to diabetic control group. Blood cholesterol was lowered significantly by dietary onion in diabetic animals. Cholesterol decrease was exclusively from LDL-VLDL fraction. Significant decrease in blood phospholipids and tr iglycerides also brought about by dietary onion. Hepatic cholesterol, triglycerides, phospholipids which were elevated under diabetic condition were countered significantly by dietary onion. Dietary capsaicin did not have any significant influence on any of the parameters tested in diabetic rats. Thus, the study reveals that onion feeding improves the metabolic status in diabetic condition, probably because of its hypoglycemic as well as hypocholesterolemic effect. (Mol Cell Biochem 175: 49–57, 1997)     

Temporal differences in bladder dysfunction caused by diabetes, diuresis, and treated diabetes in mice

Diabetic bladder dysfunction is a common complication of diabetes mellitus (DM) with poorly understood natural history. This study examined the temporal changes in bladder function 3, 9, 12, and 20 wk after induction of DM by streptozotocin (STZ) in male C57BL/6 mice compared with that in age-matched diabetic mice treated with insulin, 5% sucrose-induced diuretic mice, and sham-treated control mice. Conscious cystometrograms of mice were examined in addition to the measurements of micturition cycle. Diabetes resulted in decreased body weight. Bladder weight, urine output, bladder capacity, and compliance increased in the DM and diuretic groups. Peak voiding pressure (PVP) increased initially in both DM and diuretic mice. However, in DM mice, PVP dropped dramatically at and after 12 wk. Similar changes in the capacity, compliance, and emptying ability of the bladder were seen during the first 9 wk of the diabetes or diuresis, whereas significant decline in the emptying ability of the bladder was only seen in diabetes after 12 wk of disease in mice. Long-term insulin replacement effectively reversed most changes in bladder function. These results suggest that the transition from a compensated to a decompensated bladder dysfunction occurs 9-12 wk after induction of DM in mice by STZ.     

Bladder injection of "naked" hSlo/pcDNA3 ameliorates detrusor hyperactivity in obstructed rats in vivo

The goal of these studies was to examine the potential utility of bladder instilled K+ channel gene therapy with hSlo cDNA (i.e., the maxi-K channel) to ameliorate bladder overactivity in a rat model of partial urinary outlet obstruction. Twenty-two female Sprague-Dawley rats were subjected to partial urethral (i.e., outlet) obstruction, with 17 sham-operated control rats run in parallel. After 6 wk of obstruction, suprapubic catheters were surgically placed in the dome of the bladder in all rats. Twelve obstructed rats received bladder instillation of 100 microg of hSlo/pcDNA in 1 ml PBS during catheterization, and another 10 obstructed rats received 1 ml PBS (7 rats) or 1 ml PBS containing pcDNA only (3 rats). Two days after surgery cystometry was performed on all animals to examine the characteristics of the micturition reflex in conscious and unrestrained rats. Obstruction was associated with a three- to fourfold increase in bladder weight and alterations in virtually every micturition parameter estimate. PBS-injected obstructed rats routinely displayed spontaneous bladder contractions between micturitions. In contrast, hSlo injection eliminated the obstruction-associated bladder hyperactivity, without detectably affecting any other cystometric parameter. Presumably, expression of hSlo in rat bladder functionally antagonizes the increased contractility normally observed in obstructed animals and thereby ameliorates bladder overactivity. These initial observations indicate a potential utility of gene therapy for urinary incontinence.