The megalin/cubilin complex is responsible for the majority of serum protein reclamation in the proximal tubules. The current study examined if decreases in their renal expression, along with the albumin recycling protein FcRn, could account for proteinuria/albuminuria in the Zucker Diabetic Fatty rat model of type 2 diabetic nephropathy. Immunoblots of renal cortex samples obtained at worsening disease stages demonstrated no loss in megalin, cubilin, or FcRn, even when proteinuria was measured. Additionally, early diabetic rats exhibited significantly increased renal megalin expression when compared to controls (adjusted p < 0.01). Based on these results, the ability of insulin to increase megalin was examined in a clonal subpopulation of the Opossum Kidney proximal tubule cell line. Insulin treatments (24 hours, 100 nM) under high glucose conditions significantly increased megalin protein (p < 0.0001), mRNA (p < 0.0001), and albumin endocytosis. The effect on megalin expression was prevented with inhibitors against key effectors of insulin intracellular signaling: phosphatidylinositide 3-kinase and Akt. Studies using rapamycin to inhibit the mechanistic target of rapamycin complex 1 (mTORC1) resulted in a loss of insulin-induced megalin expression. However, subsequent evaluation demonstrated these effects were independent of initial mTORC1 suppression. The presented results provide insight into the expression of megalin, cubilin, and FcRn in type 2 diabetic nephropathy, which may be impacted by elevated insulin and glucose. Furthermore, proximal tubule endocytic activity in early diabetics may be enhanced, a process that could have a significant role in proteinuria-induced renal damage.

HA/CMC instillation during EIU may decrease the incidence of urethral stricture recurrence. In addition, the use of HA/CMC was effective in reducing pain during the early postoperative period without an adverse effect.

Results show that trichostatin A may synergistically enhance gemcitabine mediated cell cycle arrest and apoptosis, suggesting the potential of using histone deacetylase inhibitors as combination agents to enhance the antitumor effect of gemcitabine for advanced bladder cancer.

PurposeTo evaluate the efficacy and safety of the ureteroscopic management of ureteral stones immediately after a first colic attack.Materials and MethodsWe retrospectively analyzed the data of 226 patients with obstructive ureteral stones who underwent ureteroscopy with stone retrieval. The 67 patients in group A underwent ureteroscopy within 48 hours of admission to our emergency department, whereas the 159 patients in group B underwent ureteroscopy more than 48 hours after admission. The chi-square test was used to evaluate and compare stone-free status, auxiliary procedures, and complications and the Kruskal-Wallis and Fisher's exact tests were used to analyze qualitative data.ResultsMean stone sizes in groups A and B were 2.41±1.62 mm and 4.11±2.64 mm, respectively. No patient experienced a major complication during or after the procedure. Stone-free rates were 89.55% and 89.93%, respectively.ConclusionsEmergency ureteroscopy in cases of obstructive ureteral stones is both safe and effective and offers the advantages of immediate stone fragmentation and the relief of acute-onset colic pain.

PurposePercutaneous nephrolithotomy (PCNL) is the procedure of choice for treating large renal stones. Pneumatic lithotripsy (Lithoclast®) is effective regardless of the stones' composition, and ultrasonic lithotripsy allows the aspiration of small debris during lithotripsy. We investigated the efficacy and safety of PCNL via Lithoclast® alone or combined with ultrasonic lithotripsy.Materials and MethodsThirty-five (group A) and 39 (group B) patients underwent Lithoclast® PCNL and combination therapy, respectively, from May 2001 to March 2010, and the two groups were compared in terms of stone size, location, and composition; operative time; average number of treatments; hospital days; hemoglobin loss; ancillary procedures; rate of device failure; and initial and total stone-free rates.ResultsThe two groups did not differ significantly in preoperative stone size, location, or composition; the average number of treatments; or the initial and overall stone-free rates. However, combination therapy was associated with a significantly lower operative time (181±50 vs. 221±65 min, respectively, p=0.004), number of hospital days (11.6±3.8 vs. 14.2±4.4 days, respectively, p=0.009), and average hemoglobin loss (1.12±0.61 vs. 1.39±1.02 g/dl, respectively, p=0.013). Transfusions were required in 6 patients (4 and 2 in each group, respectively), but there were no significant complications related to percutaneous access. There were 2 (5.7%) mechanical failures (Lithoclast® probe fracture) in the group A and 5 (12.8%) in the group B (2 cases of suction tube obstruction, 3 cases of overheating).ConclusionsThe combination of ultrasonic lithotripter and Lithoclast® is more effective than Lithoclast® alone because it significantly decreases operative time, hemoglobin loss, and the hospital stay. This may reflect the superior power of Lithoclast® and the ability to aspirate the debris during ultrasonic lithotripsy.