Metformin abrogates the voiding dysfunction induced by prolonged methylglyoxal intake.

Methylglyoxal (MGO) is a reactive carbonyl species found at high levels in blood of diabetic patients. The anti-hyperglycemic drug metformin can scavenger MGO and reduce the formation of advanced glycation end products (AGEs). Here, we aimed to investigate if MGO-induced bladder dysfunction can be reversed by metformin. Male C57/BL6 mice received 0.5% MGO in drinking water for 12 weeks, and metformin (300 mg/kg, daily gavage) was given in the last two weeks. The bladder functions were evaluated by performing voiding behavior assays, cystometry and in vitro bladder contractions. MGO intake markedly elevated the levels of MGO and fluorescent AGEs in serum and reduced the mRNA expression and activity of glyoxalase (Glo1) in bladder tissues. Glucose levels were unaffected among groups. MGO intake also increased the urothelium thickness and collagen content of the bladder. Void spot assays in conscious mice revealed an increased void volume in MGO group. The cystometric assays in anesthetized mice revealed increases of basal pressure, non-voiding contractions frequency, bladder capacity, inter-micturition pressure and residual volume, which were accompanied by reduced voiding efficiency in MGO group. In vitro bladder contractions to carbachol, α,ß-methylene ATP and electrical-field stimulation were significantly greater in MGO group. Metformin normalized the changes of MGO and AGEs levels, Glo1 expression and activity, urothelium thickness and collagen content. The MGO-induced voiding dysfunction were all restored by metformin treatment. Our findings strongly suggest that the amelioration of MGO-induced voiding dysfunction by metformin relies on its ability to scavenger MGO, preventing its accumulation in blood.

Surgical treatment for pelvic lipomatosis using a bladder-sparing technique: A STROBE-compliant study.

The aim of this study was to report the experience and long-term efficacy of a novel surgical treatment for pelvic lipomatosis (PL) using a combination of pelvic fat mass extirpation and ureteral reimplantation.Data of 8 patients with PL who underwent pelvic fat mass extirpation and ureteral reimplantation at our hospital from September 2010 to March 2018 were retrospectively reviewed. Demographics, serum creatinine level, radiographic changes, perioperative complications, and patient-reported outcomes were evaluated.Surgeries were performed successfully without severe perioperative complications in all 8 patients. Median operating time was 150 minutes with a median estimated blood loss of 75 mL. Patients were discharged after a median of 8.5 postoperative days. Imaging studies at the first follow-up revealed varying extents of alleviation of hydronephrosis and 3 patients' urinary symptoms were gradually relieved after surgery. During a median follow-up of 48.5 months (range, 10-100 months), all patients exhibited excellent surgical outcomes without evidence of disease progression, except 1 patient who underwent radical cystectomy with Bricker ileal conduit surgery due to hydronephrosis recurrence in the 49th postoperative month.Based on these cases, pelvic fat mass extirpation and ureteral reimplantation is a safe and effective surgical treatment for PL.

Delayed diagnosis of spontaneous bladder rupture: a rare case report.

BACKGROUND: Bladder rupture caused by trauma or pelvic fracture is very common, and can be easily diagnosed. However, Spontaneous rupture of the bladder is rare. Reported by Peters PC. (Peters, Urol Clin N Am 16:279-82, 1989): The incidence of spontaneous bladder rupture is 1: 126000. During childbirth, the occurrence rate of this disease is lower than that of the former. It is very difficult to make an early diagnosis of the spontaneous rupture of the bladder during childbirth, which eventually results in high maternal mortality. Due to peritoneal reabsorption, the patient may show high levels of serum creatinine and potassium, and this would easily be misdiagnosed as acute renal failure. However, these patients have normal renal function, hence the diagnosis of renal failure is incorrect. CASE PRESENTATION: A 23 year-old female patient had her first pregnancy and delivered a full-term healthy baby girl. After delivery, the patient developed fever, oliguria, massive ascites, high serum creatinine and high serum potassium. The patient was initially diagnosed with acute renal failure, however treatment for her condition was ineffective. After further examination, the patient was diagnosed with intraperitoneal bladder rupture. The patient was treated for bladder rupture, made a full recovery and was discharged. CONCLUSIONS: Sudden onset of massive ascites and renal failure due to abnormal serum biochemical characteristics after delivery should be first diagnosed as spontaneous bladder rupture. However, bladder radiography may suggest a false negative result, hence cystoscopy should be performed to confirm the diagnosis. The ratio between ascites creatinine and serum creatinine would be helpful for early diagnosis and to determine the time of rupture. Conservative management or surgical repair should be used to treat bladder rupture.

Can baseline serum creatinine and e-GFR predict renal function outcome after augmentation cystoplasty in children?

ABSTRACT Objective To assess cut-off value of creatinine and glomerular filtration rate for augmentation cystoplasty (AC) in paediatric age-group. Materials and Methods Data of all paediatric-patients (<18 years) with small capacity bladder, in whom AC was advised between 2005-2015 were reviewed. All patients were divided in two-groups, AC-group and control-group (without AC). Creatinine and e-GFR were assessed at the time of surgery, at 6 months and at last follow-up. Renal function deterioration was defined as increase in creatinine by ≥25% from baseline value or new-onset stage-3 CKD or worsening of CKD stage with pre-operative-CKD stage-3. ROCs were plotted using creatinine and e-GFR for AC. Results A total of 94 patients with mean-age 8.9 years were included. The mean creatinine and e-GFR were 1.33mg/dL and 57.68mL/min respectively. Out of 94 patients, AC was performed in 45 patients and in the remaining 49 patients AC was not done (control-group), as they were not willing for the same. Baseline patient's characteristics were comparable in both Groups. 22 underwent gastro-cystoplasty (GC) and 25 underwent ileo-cystoplasty (IC). Decline in renal function was observed in 15 (33.3%) patients of AC-group and in 31 (63.3%) patients of control-group. Patients having creatinine ≥1.54mg/dL (P=0.004, sensitivity (S) 63.6% and specificity (s) 90.5%) at baseline and e-GFR ≤46mL/min (P=0.000, S=100% and s=85.7%) at the time of surgery had significantly increased probability of renal function deterioration on follow-up after AC. Conclusion e-GFR ≤46mL/min and creatinine ≥1.54mg/dL at time of surgery could serve as a predictor of renal function deterioration in AC in paediatric patients.

Can baseline serum creatinine and e-GFR predict renal function outcome after augmentation cystoplasty in children?

OBJECTIVE: To assess cut-off value of creatinine and glomerular filtration rate for augmentation cystoplasty (AC) in paediatric age-group. MATERIALS AND METHODS: Data of all paediatric-patients (<18 years) with small capacity bladder, in whom AC was advised between 2005-2015 were reviewed. All patients were divided in two-groups, AC-group and control-group (without AC). Creatinine and e-GFR were assessed at the time of surgery, at 6 months and at last follow-up. Renal function deterioration was defined as increase in creatinine by ≥25% from baseline value or new-onset stage-3 CKD or worsening of CKD stage with pre-operative-CKD stage-3. ROCs were plotted using creatinine and e-GFR for AC. RESULTS: A total of 94 patients with mean-age 8.9 years were included. The mean creatinine and e-GFR were 1.33mg/dL and 57.68mL/min respectively. Out of 94 patients, AC was performed in 45 patients and in the remaining 49 patients AC was not done (control-group), as they were not willing for the same. Baseline patient's characteristics were comparable in both Groups. 22 underwent gastro-cystoplasty (GC) and 25 underwent ileo-cystoplasty (IC). Decline in renal function was observed in 15 (33.3%) patients of AC-group and in 31 (63.3%) patients of control-group. Patients having creatinine ≥1.54mg/dL (P=0.004, sensitivity (S) 63.6% and specificity (s) 90.5%) at baseline and e-GFR ≤46mL/min (P=0.000, S=100% and s=85.7%) at the time of surgery had significantly increased probability of renal function deterioration on follow-up after AC. CONCLUSION: e-GFR ≤46mL/min and creatinine ≥1.54mg/dL at time of surgery could serve as a predictor of renal function deterioration in AC in paediatric patients.

Changes of urinary bladder contractility in high-fat diet-fed mice: the role of tumor necrosis factor-α.

OBJECTIVES: To study the role of tumor necrosis factor-α in bladder dysfunction associated with obesity. METHODS: Male 8-week-old C57BL/6J mice were divided into three groups: (i) control mice; (ii) vehicle-treated high-fat diet-fed mice; and (iii) etanercept-treated high-fat diet-fed mice. High-fat diet feeding lasted for 12 weeks, vehicle or etanercept (0.8 mg/kg/day, a tumor necrosis factor-α antagonist) treatment was given during the last 4 weeks. At the end of the treatment period, serum tumor necrosis factor-α, total cholesterol, triglyceride and blood glucose were measured. Bladder strip contractile responses to 1 µmol/L acetylcholine or 50 mmol/L KCl were studied in an organ bath. Bladder protein kinase Cζ, nuclear factor-κB and intercellular adhesion molecule-1 expressions were analyzed using western blots. RESULTS: Serum levels of tumor necrosis factor-α total cholesterol, triglyceride and glucose were significantly elevated in high-fat diet-fed mice; and the levels were not ameliorated by etanercept treatment. High-fat diet-fed mouse bladder showed reduced contractile responses to acetylcholine and KCl stimulation accompanied by high expression levels of phospho-protein kinase Cζ, nuclear nuclear factor-κB and intercellular adhesion molecule-1. Etanercept restored normal bladder contractile responses, as well as protein kinase Cζ nuclear factor-κB and intercellular adhesion molecule-1 expressions. CONCLUSIONS: A high-fat diet induces bodyweight gain, hyperlipidemia and hyperglycemia in mice. Elevated serum tumor necrosis factor-α level associated with increased protein kinase Cζ phosphorylation, nuclear factor-κB nuclear migration, intercellular adhesion molecule-1 expression and impaired muscle contractility are shown in the high-fat diet-fed mouse bladder. Tumor necrosis factor-α antagonist treatment restores normal bladder contractility, and protein kinase Cζ nuclear factor-κB and intercellular adhesion molecule-1 levels.

Hypercreatinemia: think beyond acute kidney injury.

Urinary bladder rupture associated with severe hypercreatinemia is a rare clinical presentation. We herein report a 60-year-old interesting patient who was found to have intraperitoneal bladder rupture and pseudo-renal failure. High rate of suspicion and timely diagnosis is the key in management of this condition, which led to complete recovery in our patient.

[Leucoplakia vesicae in females: diagnosis and treatment].

Sixty patients suffering from leucoplakia vesicae (LV) were examined using cystoscopy with biopsy of the urinary bladder wall, blood enzyme immunoassay for detection of antibodies to agents of sexually transmitted infections (STI), uroflowmetry, culture analysis of cervical canal and mucosa samples for STI. As shown by a pathomorphological examination of the vesical mucosa biopsy specimens, long-term persistence of pathogenic (chlamydia, trichomonades) and opportunistic (mycoplasma, ureaplasma, fungi) flora underlies development of LV. Morphogenesis of LV is characterized by hyperplastic reactions of urothelium and its metaplasy in laminated squamous keratosic epithelium, often with para- and dyskeratosis, developing in the presence of inflammatory reactions in the lamina in the presence of persisting infection. In LV, specific infection agents are often found in the urogenital tract. The spectrum of these agents is identical for samples from the cervical canal and vesical mucosa from leucoplakia foci. Vesical mucosa is most frequently contaminated with Mycoplasma hominis (57.2%), Candida albicans (51.4%), Ureaplasma urealiticum (37.1%) and Trichomonas vaginalis (22.9%). Associations of the infection agents are detected in 70% of LV patients. Persistent dysuria is a basic clinical symptom of leucoplakia. The following therapeutic measures should be taken: transurethral coagulation of the vesical mucosa, intravesical therapy, immunocorrection, antibacterial treatment by standard schemes or according to the isolated flora sensitivity.

Cerebrospinal fluid leakage in intracranial hypotension syndrome: usefulness of indirect findings in radionuclide cisternography for detection and treatment monitoring.

PURPOSE: To evaluate indirect findings of cerebrospinal fluid (CSF) leakage on radionuclide cisternography and their changes after treatment. MATERIALS AND METHODS: This study was approved by the hospital's institutional review board and informed consent was obtained before each examination. A total of 67 patients who were clinically suspected of spontaneous intracranial hypotension (SIH) syndrome underwent radionuclide cisternography, and 27 patients who had direct findings of CSF leakage on radionuclide cisternography were selected for this evaluation. They were 16 males and 11 females, aged between 26 and 58 years. Sequential images of radionuclide cisternography were acquired at 1, 3, 5, and 24 hours after injection. We assessed the presence or absence of 4 indirect findings; early visualization of bladder activity, no visualization of activity over the brain convexities, rapid disappearance of spinal activity, and abnormal visualization of the root sleeves. Changes of the direct and indirect findings after treatment were also evaluated in 14 patients who underwent epidural blood patch treatment. RESULTS: Early visualization of bladder activity was found in all 27 patients. Seven of 27 (25.9%) patients showed no activity over the brain convexities. Rapid disappearance of spinal activity and abnormal root sleeve visualization were present in 2 (7.4%) and 5 (18.5%) patients, respectively. After epidural blood patch, both direct CSF leakage findings and indirect findings of early visualization of bladder activity had disappeared or improved in 12 of 14 patients (85.7%). The other indirect findings also disappeared after treatment in all cases. CONCLUSION: Indirect findings of radionuclide cisternography, especially early visualization of bladder activity, may be useful in the diagnosis and posttreatment follow-up of CSF leakage.

[The results of orthotopic plastic reconstruction of the urinary bladder with gastric and iliac graft].

To compare the results of postoperative plastic reconstruction of the urinary bladder (PRUB) with gastric and iliac graft, we studied 205 patients (150 males, 73.2%; 55 females, 26.8% aged 23-72 years, mean age 62.1 +/- 0.5 years) who had undergone orthotopic PRUB. Artificial bladder was created in 26 (12.7%) patients of a stomach pedicle segment, in 174 (84.9%)--of a detubulated iliac segment, in 5 (2.4%)--of a sigmoid segment. Early and late postoperative complications in using small intestinal segment reached 14.0 and 10.4%, respectively, lethality being 2.6%; in using gastric segment made up 3.9 and 8.7%, respectively, lethal outcomes were absent. Patients after PRUB had neither disorders of acid-base balance nor defects in electrolytic balance of blood. Urodynamic parameters were close to physiological ones. Thus, satisfactory clinical and functional results of urinary bladder orthotopic reconstruction even in long-term follow-up confirm advantages of orthotopic reconstruction of the lower urinary tracts in diseases of the urinary bladder.

Clinico-pathological findings in cattle exposed to chronic bracken fern toxicity.

AIM: To describe changes in blood and urine analytes in a large group of cattle exposed to chronic bracken fern toxicity, in order to identify parameters of potential diagnostic value. METHODS: The study was conducted on two livestock farms on which bovine enzootic haematuria (BEH) was known to occur; Farm A grazed a local breed of cows and Farm B grazed Friesians. Group A1 comprised 66 cows from Farm A, Group B 54 cows from Farm B, and Group A2 13 heifers from Farm A. Ten healthy cows were used as controls. A complete physical examination was performed (Group A1), and blood (all groups) and urine (Groups A1 and B) samples were collected. Necropsies and histopathology were undertaken on four cows. RESULTS: Anaemia, leucopenia, monocytosis, thrombocytopenia, hypergammaglobulinaemia, microhaematuria and proteinuria were detected. Multivariate statistical analyses established three phases of the disease of increasing severity; an initial phase, characterised by an extremely high monocytosis and otherwise normal parameters; an intermediate phase, characterised by monocytosis and moderate changes to other analytes; and a final phase, characterised by normal levels of monocytes and many changes to other analytes. CONCLUSIONS AND CLINICAL RELEVANCE: Monocytosis, detected in 31% of the younger animals, could represent an initial response to consumption of bracken fern and might be useful as an early haematological marker of BEH.

Detection of cerebrospinal fluid leakage in intracranial hypotension with radionuclide cisternography and blood activity monitoring.

UNLABELLED: Radionuclide cisternography is an indispensable examination to detect cerebrospinal fluid (CSF) leakage in patients suspected of having spontaneous intracranial hypotension (SIH). However, it sometimes fails to demonstrate the site of CSF leakage, and in such cases, early bladder visualization is utilized for the diagnosis of SIH as an indirect finding. The aim of this work is to improve the diagnostic ability of radionuclide cisternography and to reevaluate the reliability of early bladder visualization as an indirect finding of CSF leakage. METHODS: We obtained serial images during the first hour after injection as well as the following time points in 4 patients with SIH and 5 with normal pressure hydrocephalus (NPH) as a control. We also performed blood sampling over time to measure blood radioactivity concentrations. RESULTS: All 4 patients with SIH demonstrated leakage, 2 of 4 within one hour after injection. Bladder visualization was observed falsely in 4 of 5 patients with NPH, considered to be the result of a lumbar puncture complication. In this false bladder visualization, blood radioactivity showed a more rapid raise and fall than in CSF leakage of SIH. CONCLUSIONS: The combination of radionuclide cisternography, including early time points and blood sampling, may enable accurate diagnosis of SIH.

Assessment of murine bladder permeability with fluorescein: validation with cyclophosphamide and protamine.

OBJECTIVES: Bladder hyperpermeability should result in elevated blood levels of intravesically administered agents. Reabsorption from a hyperpermeable bladder should result in prolonged urinary excretion of an agent after parenteral administration. To test these hypotheses, urinary clearance and plasma levels of sodium fluorescein (NaF) were measured in mice before and during cyclophosphamide (CYP) and protamine-induced hemorrhagic cystitis. METHODS: To measure the plasma uptake of NaF from the bladder, 10 mg/mL NaF was instilled, either by catheter or retrograde urethral infusion, 15 minutes before retro-orbital or ventricular sampling. The plasma levels were measured 24 hours and 14 days after exposure to CYP 300 mg/kg or 15 minutes after instillation of protamine 10 mg/mL. Hourly urine concentrations were measured immediately after intraperitoneal administration of 10 mg/kg NaF. Pretreatment samples were compared with those obtained 24 hours after intraperitoneal administration of 300 mg/kg CYP. RESULTS: Urinary NaF excretion was delayed in CYP-exposed mice. A bi-exponential model provided an appropriate fit of the data, both before and after CYP administration. The plasma levels of NaF were significantly elevated at 24 hours and 14 days after CYP exposure when sampled by ventricular nick or retro-orbitally. The median concentration of fluorescein in the protamine-treated mice was significantly higher than in the control mice. CONCLUSIONS: Fluorescein can be used to measure alterations in bladder permeability after bladder mucosal injury in mice. Urinary excretion of NaF is a bi-exponential process that is delayed after bladder mucosal injury, presumably because of increased mucosal permeability and resorption from the urine into the bloodstream.

Cytokeratins as serum markers in egyptian bladder cancer. A comparison of CYFRA 21-1, TPA and TPS.

Cytokeratins (CKs) have been shown to be overexpressed in bladder cancer and to be valuable as tumor markers. The present study was designed to evaluate the single and combined use of three cytokeratin fragments, CYFRA 21-1, TPA, and TPS, in serum of Egyptian bladder cancer patients. The study subjects comprised 40 healthy controls, 30 patients with benign bladder diseases, and 60 patients with histologically confirmed primary bladder cancer. The cutoff was set at 95% specificity versus benign bladder diseases, resulting in cutoff values of 2.93 ng/mL for CYFRA 21-1, 158 U/L for TPA and 143.7 ng/mL for TPS. With 41% true positive results CYFRA 21-1 had a higher sensitivity than TPA (32%) and TPS (27%). Evaluation by histological findings revealed a highest sensitivity of CYFRA 21-1 (46%) in transitional cell carcinoma (TCC) followed by TPA (27%) and TPS (21%). Also in adenocarcinoma CYFRA 21-1 showed the highest sensitivity (38%) followed by TPA (32%) and TPS (28%). A high percentage (41.6%) of Egyptian bladder cancers is represented by squamous cell carcinoma (SCC). In this population TPS showed the highest sensitivity (69%), followed by CYFRA 21-1 (54%) and TPA (41 %). The sensitivity of each of the three markers increased with advancing tumor stage and increasing tumor grade. Combined use of two of the three markers did not raise the sensitivities obtained by single determination of CYFRA 21-1. The present study suggests that serum CYFRA 21-1 could be a marker of choice in bladder cancer.

Clot retention and spontaneous rupture with secondary pneumatosis of bladder wall following routine cystoscopy.

In this article we report an unusual case of spontaneous rupture of bladder wall following office-cystoscopy. It took place in a patient who suffered from low-stage highgrade carcinoma of bladder with the different aggressive behavior. Finally, he underwent radical cystectomy, which showed micropapillary carcinoma and pneumatosis within the bladder wall. The cause of the latter finding is rather puzzling and has been never reported previously.