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10.1128/AAC.02391-16 http://scihub22266oqcxt.onion/10.1128/AAC.02391-16 C5365704!5365704!28096166     free     free     free Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Antimicrob+Agents+Chemother 2017 ; 61 (4): ä Nephropedia Template TP {{tp|p=28096166|t=2017. Role of Renal Drug Exposure in Polymyxin B-Induced Nephrotoxicity |pdf=|usr=}}{{28096166}} gab.com Text Role of Renal Drug Exposure in Polymyxin B-Induced Nephrotoxicity JO: Antimicrob Agents Chemother http://www.kidney.de/pget.php?&tw=1&pmid=28096166 #FOAvip Despite dose-limiting nephrotoxic potentials, polymyxin B has reemerged as the last line of therapy against multidrug-resistant Gram-negative bacterial infections. However, the handling of polymyxin B by the kidneys is still not thoroughly understood. The objectives of this study were to evaluate the impact of renal polymyxin B exposure on nephrotoxicity and to explore the role of megalin in renal drug accumulation. Sprague-Dawley rats (225 to 250 g) were divided into three dosing groups, and polymyxin B was administered (5 mg/kg, 10 mg/kg, and 20 mg/kg) subcutaneously once daily. The onset of nephrotoxicity over 7 days and renal drug concentrations 24 h after the first dose were assessed. The effects of sodium maleate (400 mg/kg intraperitoneally) on megalin homeostasis were evaluated by determining the urinary megalin concentration and electron microscopic study of renal tissue. The serum/renal pharmacokinetics of polymyxin B were assessed in megalin-shedding rats. The onset of nephrotoxicity was correlated with the daily dose of polymyxin B. Renal polymyxin B concentrations were found to be 3.6 ± 0.4 ?g/g, 9.9 ± 1.5 ?g/g, and 21.7 ± 4.8 ?g/g in the 5-mg/kg, 10-mg/kg, and 20-mg/kg dosing groups, respectively. In megalin-shedding rats, the serum pharmacokinetics of polymyxin B remained unchanged, but the renal exposure was attenuated by 40% compared to that of control rats. The onset of polymyxin B-induced nephrotoxicity is correlated with the renal drug exposure. In addition, megalin appears to play a pivotal role in the renal accumulation of polymyxin B, which might contribute to nephrotoxicity. Twit Text FOAVip Role of Renal Drug Exposure in Polymyxin B-Induced Nephrotoxicity ????Antimicrob Agents Chemother http://www.kidney.de/pget.php?&tw=1&pmid=28096166 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28096166 #FOAvip English Wikipedia <ref>{{Cite pmid|28096166}}</ref> Role of Renal Drug Exposure in Polymyxin B-Induced Nephrotoxicity #MMPMID28096166 Manchandani P; Zhou J; Babic JT; Ledesma KR; Truong LD; Tam VH Antimicrob Agents Chemother 2017[Apr]; 61 (4): ä PMID28096166show ga Despite dose-limiting nephrotoxic potentials, polymyxin B has reemerged as the last line of therapy against multidrug-resistant Gram-negative bacterial infections. However, the handling of polymyxin B by the kidneys is still not thoroughly understood. The objectives of this study were to evaluate the impact of renal polymyxin B exposure on nephrotoxicity and to explore the role of megalin in renal drug accumulation. Sprague-Dawley rats (225 to 250 g) were divided into three dosing groups, and polymyxin B was administered (5 mg/kg, 10 mg/kg, and 20 mg/kg) subcutaneously once daily. The onset of nephrotoxicity over 7 days and renal drug concentrations 24 h after the first dose were assessed. The effects of sodium maleate (400 mg/kg intraperitoneally) on megalin homeostasis were evaluated by determining the urinary megalin concentration and electron microscopic study of renal tissue. The serum/renal pharmacokinetics of polymyxin B were assessed in megalin-shedding rats. The onset of nephrotoxicity was correlated with the daily dose of polymyxin B. Renal polymyxin B concentrations were found to be 3.6 ± 0.4 ?g/g, 9.9 ± 1.5 ?g/g, and 21.7 ± 4.8 ?g/g in the 5-mg/kg, 10-mg/kg, and 20-mg/kg dosing groups, respectively. In megalin-shedding rats, the serum pharmacokinetics of polymyxin B remained unchanged, but the renal exposure was attenuated by 40% compared to that of control rats. The onset of polymyxin B-induced nephrotoxicity is correlated with the renal drug exposure. In addition, megalin appears to play a pivotal role in the renal accumulation of polymyxin B, which might contribute to nephrotoxicity. äRole of Renal Drug Exposure in Polymyxin B-Induced Nephrotoxicity (epmc).pdf DeepDyve Pubget Overpricing