American journal of nephrology
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Randomized Controlled Trial Multicenter Study
Assessment of the efficacy and safety of intravenous conivaptan in euvolemic and hypervolemic hyponatremia.
Most cases of hyponatremia--serum sodium concentration ([Na+]) < 135 mEq/l (< 135 mM)--are associated with an elevated plasma arginine vasopressin level. This study investigated the efficacy and tolerability of intravenous conivaptan (YM087), a vasopressin V1A/V2-receptor antagonist, in treating euvolemic and hypervolemic hyponatremia. ⋯ Among patients with euvolemic or hypervolemic hyponatremia, 4-day intravenous infusion of conivaptan 40 mg/day significantly increased serum [Na+] and was well tolerated.
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Upregulation of transforming growth factor beta (TGF-beta)/Smad signaling has been implicated in the primary pathogenesis of renal fibrosis. The ubiquitin-proteasome pathway has an important influence on TGF-beta signaling through regulating Smad degradation. As E3 ubiquitin ligases, both Arkadia and Smurf2 are involved in this prosess. In this study, we focused on Arkadia, Smurf2, Smad7, and TGF-beta type I receptor (TbetaRI), principal molecules in the regulation of TGF-beta signaling, to understand the regulatory mechanism of ubiquitin-proteasomal degradation of TGF-beta signaling in the pathogenesis of renal fibrosis. ⋯ Reduction of Smad7 resulting from ubiquitin-dependent degradation may be mainly attributed to Arkadia, and Arkadia-Smad7-mediated positive regulation of TGF-beta signaling may play a promoting role in the progression of tubulointerstitial fibrosis.