IG, Whiteside CI. Reactive oxygen species, PKC-␤ 1, and PKCmediate high-glucose-induced vascular endothelial growth factor expression in mesangial cells.

Uterine leiomyomas are underrecognized as a cause of acute urinary retention (AUR) in women. The objective of this study was to present a case series and systematic review of the literature, to elucidate the pathogenesis of leiomyoma-related AUR, and to suggest management strategies. We included patients presenting with AUR and uterine leiomyomas at our institution between January 2011 and December 2013. Further, we systematically searched the Cochrane Library (from 1898 to June 2014), EMBASE (from 1947 to June 2014), and MEDLINE (from 1946 to June 2014) databases according to the PRISMA guidelines. A total of six patients with AUR and leiomyomas presented to our institution. Through the systematic review, another 31 cases of AUR were identified. Combined patient ages ranged from 25 to 75 years. Uterine size ranged from 10 to 22 weeks on physical examination and from 5.5 to 26 cm on imaging. The dominant leiomyoma size ranged from 5.7 to 22.4 cm. Significant risk factors were posterior or fundal leiomyoma position and the presence of a retroverted uterus. Proposed mechanisms for leiomyoma-related AUR include proximal urethra or bladder-neck compression, premenstrual pelvic congestion, vascular steal effect, and compression of pudendal or sacral nerves. Patients were treated with hysterectomy, myomectomy, uterine fibroid embolization, hormones, or by conservative management alone. In the absence of neurologic disorders or other risk factors, neither urodynamic studies nor neuromuscular testing seem to contribute to diagnosis or guide management in women with uterine leiomyomas and AUR. Patients presenting to gynecologists seem to experience shorter times to diagnosis and treatment compared with other specialties. It is essential to recognize leiomyomas as a potential cause of AUR in order to reduce unnecessary testing and delays in diagnosis and management.

In high glucose, glomerular mesangial cells (MCs) demonstrate impaired Ca(2+) signaling in response to seven-transmembrane receptor stimulation. To identify the mechanism, we first postulated decreased release from intracellular stores. Intracellular Ca(2+) was measured in fluo-3-loaded primary cultured rat MCs using confocal fluorescence microscopy. In high glucose (HG) 30 mM for 48 h, the 25 nM ionomycin-stimulated intracellular Ca(2+) response was reduced to 82% of that observed in normal glucose (NG). In NG 5.6 mM, Ca(2+) responses to endothelin (ET)-1 and platelet-derived growth factor (PDGF) were unchanged in cells cultured in 50 nM Ca(2+) vs. 1.8 mM Ca(2+). Depletion of intracellular Ca(2+) stores with thapsigargin eliminated ET-1-stimulated Ca(2+) responses. Incubation in 30 mM glucose (HG) for 48 h or stimulation with phorbol myristate acetate (PMA) for 10 min eliminated the Ca(2+) response to ET-1 but had no effect on the PDGF response. Downregulation of protein kinase C (PKC) with 24-h PMA or inhibition with Gö6976 in HG normalized the Ca(2+) response to ET-1. Because ET-1 and PDGF stimulate Ca(2+) signaling through different phospholipase C pathways, we hypothesized that, in HG, PKC selectively phosphorylates and inhibits PLC-beta(3). Using confocal immunofluorescence imaging, in NG, a 1.6- to 1.7-fold increase in PLC-beta(3) Ser(1105) phosphorylation was observed following PMA or ET-1 stimulation for 10 min. In HG, immunofluorescent imaging and immunoblotting showed increased PLC-beta(3) phosphorylation, without change in total PLC-beta(3), which was reversed with 24-h PMA or Gö6976. We conclude that reduced Ca(2+) signaling in HG cannot be explained by reduced Ca(2+) stores but is due to conventional PKC-dependent phosphorylation and inactivation of PLC-beta(3).