Melatonin enhances endogenous heme oxygenase-1 and represses immune responses to ameliorate experimental murine membranous nephropathy

Abstract: Idiopathic membranous nephropathy (MN), an autoimmune‐mediated glomerulonephritis, is one of the most common causes of nephrotic syndrome in adults. Therapeutic agents for MN remain ill defined. We assessed the efficacy of melatonin therapy for MN. Experimental murine MN was induced with cationic bovine serum albumin, and the mice were immediately administered 20 mg/kg melatonin or phosphate‐buffered saline subcutaneously once a day. Disease severity was verified by examining serum and urine metabolic profiles and renal histopathology. The expression of cytokines and oxidative stress markers, cell apoptosis, and the associated mechanisms were also determined. Mice treated with melatonin displayed a significant reduction in proteinuria and a marked amelioration of glomerular lesions, with attenuated immunocomplex deposition. The subpopulations of T cells were not altered, but the CD19⁺ B‐cell subpopulation was significantly reduced in the MN mice treated with melatonin. The expression of cytokine mRNAs in splenocytes indicated that melatonin reduced the expression of proinflammatory cytokines and increased the expression of anti‐inflammatory cytokines (interleukin 10). The production of reactive oxygen species and TUNEL‐positive apoptotic cells in the kidney were also significantly reduced in the melatonin‐treated MN mice. Melatonin also upregulated heme oxygenase 1 (HO1) and ameliorated MN. The blockade of HO1 expression with SnPP, a HO1 inhibitor, attenuated HO1 induction by melatonin and thus mitigated its renoprotective effects during MN. Our results suggest that melatonin treatment ameliorates experimental MN via multiple pathways, including by its antioxidative, antiapoptotic, and immunomodulatory effects. Melatonin should be considered a potential therapeutic intervention for MN in the future.     

Diode laser (980 nm) enucleation of the prostate: a promising alternative to transurethral resection of the prostate

With good hemostatic ability, the end-firing continuous-wave diode laser at 980 nm was used to enucleate the prostate (DiLEP) for the treatment of benign prostatic obstruction (BPO). The study compared the patients' demographics and surgical outcomes between DiLEP and transurethral resection of the prostate (TURP). Patients with significant BPO and a total prostatic weight of 40 g or more who had undergone DiLEP (n = 74) or TURP (n = 52) during the same period at our hospital were enrolled for analysis. DiLEP was performed by a single surgeon (Yang), and TURP by three surgeons (Yang, Hsieh and Chang). The 4-U incision technique was developed for DiLEP. The diode laser ensured bloodless incision followed by blunt dissection using the resectoscope and laser fiber as an 'index finger' to enucleate the prostate. To prevent unexpected deep thermal damage, the power of the laser was set at 80 W and the laser beam was directed towards the bladder neck and not towards the prostatic capsule. Demographic data and perioperative parameters were comparable between the two groups, except that DiLEP resulted in a significantly lower drop in hemoglobin level (0.9 ± 1.0 vs. 1.6 ± 2.4 g/dl, p = 0.03), shorter catheterization time (41.2 ± 19.9 vs. 67.7 ± 33.3 h, p = 0.01), and shorter postoperative stay (2.9 ± 1.9 vs. 4.1 ± 6.2 days, p = 00.01). Delayed postoperative sloughing of necrotic tissue was not observed in the DiLEP group. Improvements in voiding parameters were comparable between the groups, and were sustained during a follow-up of up to 1 year. DiLEP provided better hemostasis than TURP as evidenced by less blood loss. The role of DiLEP treating BPO requires further investigation.