7.Effect of polyethylene oxide on renal hemodynamics in rabbits with endotoxin shock.
Qin FANG ; Zhenhua HU ; Zhongqing CHEN ; Xingxing DUAN ; Hui CHEN ; Weijun FU ; Hongyun WEI
Journal of Southern Medical University 2012;32(5):718-721
OBJECTIVETo investigate the effect of polyethylene oxide (PEO) on renal blood flow and its renoprotective effect in rabbits with endotoxin sepsis.
METHODSTwenty normal New Zealand white rabbits were randomly divided into normal saline (NS) group and PEO group (n=10), and endotoxin shock was induced by an intravenous injection of 0.6 mg/kg lipopolysaccharide. Resuscitation was performed when the blood pressure of the rabbits showed a 30% decline, using NS (in NS group) or the mixture of equal volumes of NS and 20 ng/g PEO (in PEO group) perfused at the rate of 5 ml/kg per hour. Before and during shock and at 1 h after resuscitation, the renal hemodynamics was monitored by ultrasound and the venous blood was extracted to examine the renal functions. The heart rate and arterial blood pressure were monitored throughout the experiment.
RESULTSThe rabbits in both groups showed a significantly lower renal artery blood flow velocity during the shock (P<0.05) with significantly increased pulsatility index (PI) and resistance index (RI) compared with those before the shock. One hour after resuscitation, the blood flow velocity in the renal arteries at all levels and the tertiary veins were reduced in NS group without obvious reduction of the PI and RI; in PEO group, the blood flow velocities in the renal arteries increased significantly compared to those before shock (P<0.05), and the PI and RI of the tertiary arteries were significantly lower than those in NS group (P<0.05). In both groups, BUN and Cr increased during endotoxin shock stage, and 1 h after resuscitation, PEO group showed significantly lower BUN and Cr levels than NS group (P<0.05).
CONCLUSIONA small dose of PEO can significantly promote renal perfusion in rabbits with septic shock, thus offering renoprotective effect against early damage in septicopyemia and septic shock.
Animals ; Hemodynamics ; Polyethylene Glycols ; pharmacology ; therapeutic use ; Rabbits ; Renal Circulation ; Shock, Septic ; drug therapy ; physiopathology
8.Advances of modified IL-2 molecules in drug development.
Lijing HUANG ; Xiaohan MA ; Chenhui LI ; Hongquan WANG
Chinese Journal of Biotechnology 2022;38(9):3279-3290
Interleukin-2 (IL-2) is one of the most important regulators in immune system, as it plays an essential part both in immune activation and suppression. However, as the first immunotherapy drug approved for the treatment of cancer, IL-2 is limited in clinical application by the serious adverse reactions. The long-felt needs in clinical practice, including prolonged half-lives, T cell subset specificity, and toxicity reduction can be achieved by polyethylene glycol (PEG) modification, Fc fusing, or protein mutation of IL-2. NKTR-214, the most advanced IL-2 pathway-targeted agent in clinical development for oncology, shows exciting results in treatment of melanoma in combination with nivolumab. At the same time, many more other modified molecules against cancer and autoimmune diseases are being tested in clinical research, an exciting future lying ahead for IL-2 therapeutics.
Drug Development
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Humans
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Immunotherapy/methods*
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Interleukin-2/therapeutic use*
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Melanoma/drug therapy*
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Nivolumab/therapeutic use*
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Polyethylene Glycols
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