Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetic kidney disease is associated with monocyte chemoattractant CC chemokine ligand 2 (CCL2)-dependent glomerular and interstitial macrophage recruitment. In addition, nephropathy is delayed in Ccl2 mutant diabetic mice. However, whether the late onset of therapeutic Ccl2 blockade modulates the progression of advanced diabetic nephropathy remains unknown. We addressed this question by antagonizing Ccl2 with mNOX-E36-3'PEG, an anti-Ccl2 L-enantiomeric RNA aptamer (ie, a Spiegelmer), which binds murine Ccl2 and blocks the recruitment of ex vivo-labeled macrophages to the kidneys of db/db mice with type 2 diabetes. We injected mNOX-E36-3'PEG subcutaneously at a dose of 50 mg/kg three times per week into uninephrectomized (1K) db/db mice with advanced glomerulopathy from 4 to 6 months of age. mNOX-E36-3'PEG reduced the number of glomerular macrophages by 40% compared with nonfunctional (control) Spiegelmer-treated 1K db/db mice. This result was associated with protection from diffuse glomerulosclerosis and significantly improved the glomerular filtration rate. mNOX-E36-3'PEG also reduced renal Ccl2 mRNA and protein expression compared with control Spiegelmer-treated 1K db/db mice of the same age. Together, the late onset of therapeutic Ccl2 blockade, eg, with specific Spiegelmers, offers protection from diffuse glomerulosclerosis in type 2 diabetic db/db mice and, thus, may represent a novel therapeutic strategy for advanced glomerulosclerosis.
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PMID:Late onset of Ccl2 blockade with the Spiegelmer mNOX-E36-3'PEG prevents glomerulosclerosis and improves glomerular filtration rate in db/db mice. 1825 51

Pegylated interferon (PEG-IFN) is now the standard treatment for chronic hepatitis C. But, there are few reports about patients with end stage renal disease, and treatment protocol for HCV infection has not been determined, particularly in patients on peritoneal dialysis. We experienced a case of a peritoneal dialysis patient with chronic hepatitis C who was successfully treated with PEG-IFN monotherapy. A 50-year old man was undergoing peritoneal dialysis because of diabetic nephropathy. Considering that his HCV genotype was 2, we decided to treat him with PEG-IFN alpha-2a monotherapy 4 month after the beginning of peritoneal dialysis. We adopted a 90 mg of PEG-IFN administration. After the injection of PEG-IFN, dialysate concentration of PEG-IFN did not change significantly. HCV-RNA disappeared at the 4th week and sustatined virus response was achieved thereafter. No side effects were observed during the treatment of 24 weeks. PEG-IFN monotherapy with dose modification may be a safe and effective treatment for HCV infection in patients undergoing peritoneal dialysis.
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PMID:[A case of pegylated interferon alpha-2a monotherapy in a peritoneal dialysis patient with chronic hepatitis C]. 2187 27

We report a 66-year-old man with chronic hepatitis caused by hepatitis type C virus of genotype-1b and high-viral-load combined with cryoglobulinemia and advanced diabetic nephropathy in whom we successfully achieved viral removal and eradication by DFPP (VRAD). The dose of PEG-interferon was reduced to 70 mg/week due to thrombocytopenia. Rivavirin was discontinued at day 21 due to anemia. Even with treatment of PEG-interferon alone, the condition was judged to be sustained viral remission at the end of the observation. This is a successful report of VRAD in a combined case of diabetic and HCV-related cryoglobulin-nephropathy with nephrotic syndrome. The therapeutic effect of IFN seemed to be efficiently enhanced by concomitant DFPP (VRAD therapy).
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PMID:A case of chronic hepatitis C with nephrotic diabetic nephropathy who achieved sustained viral remission by double-filtration plasmapheresis and interferon combination therapy. 2286 24

The poly(ethylene glycol)-b-brush poly(l-lysine) polymer (PEG-b-(PELG50-g-PLL3)) was synthesized and evaluated as a nanocarrier for prolonging delivery of exenatide through the abdominal subcutaneous injection route. The isoelectric point of exenatide was 4.86, and exenatide could combine with PEG-b-(PELG50-g-PLL3) polymers via electrostatic interactions at pH 7.4. This polymer was a good candidate for achieving prolonged drug delivery for exenatide, considering its high molecular weight. Besides the physicochemical characterization of the polymer, in vitro and in vivo applications were researched as a sustained exenatide delivery system. In the in vitro release research, 20.16%-76.88% of total exenatide was released from the PEG-b-(PELG50-g-PLL3) polymer within 7 days. The synthesized block-brush polymers and exenatide-block-brush polymers were analyzed by nuclear magnetic resonance spectroscopy, gel permeation chromatography, transmission electron microscopy, nanoparticle size instrument, and scanning electron microscopy. The best formulation was selected for in vivo experimentation to achieve blood glucose control in diabetic rat models using free exenatide as the control. The hypoglycemic action of the formulation following subcutaneous injection in diabetic rats lasted 7 days, and the results indicated that exenatide-block-brush polymers demonstrate enhanced long-acting hypoglycemic action. Besides the hypoglycemic action, exenatide-block-brush polymers significantly alleviated diabetic nephropathy via improving renal function, decreasing oxidative stress injury, decreasing urinary albumin excretion rate, mitigating albumin/creatinine ratio, reducing blood lipids, abating kidney index, weakening apoptosis, and downregulating expression of connective tissue growth factor. All of the results suggested that PEG-b-(PELG50-g-PLL3) polymers could be used as potential exenatide nanocarriers, with efficient encapsulation and sustained release.
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PMID:Preparation of exenatide-loaded linear poly(ethylene glycol)-brush poly(l-lysine) block copolymer: potential implications on diabetic nephropathy. 2872 Oct 43

Diabetic nephropathy (DN) is a frequent and severe microvascular complication associated with oxidative stress of diabetes mellitus. A novel astaxanthin-based natural antioxidant nanosystem, namely AST-GLU-LIP, with preferential renal uptake and bioavailability were prepared and applied for treatment of diabetic nephropathy in rats. Our results of kidney-targeted evaluation showed that glucose-PEG600-DSPE ligand modified AST liposomes could be specifically transported by overexpressed GLUT1 on the membrane of glomerular mesangial cells and achieved excellent kidney-targeted drug delivery. In addition, the results of pharmacodynamics and therapeutics in DN rats demonstrated that AST-GLU-LIP could improve the bioavailability and antioxidant capacity of AST to scavenge redundant ROS induced by oxidative stress. AST-GLU-LIP could also significantly improve the renal pathological morphology to protect the kidney as a therapeutic drug for diabetic nephropathy.
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PMID:Kidney-targeted astaxanthin natural antioxidant nanosystem for diabetic nephropathy therapy. 3293 79