Oxidative protein labeling in mass-spectrometry-based proteomics

Oxidation of proteins and peptides is a common phenomenon, and can be employed as a labeling technique for mass-spectrometry-based proteomics. Nonspecific oxidative labeling methods can modify almost any amino acid residue in a protein or only surface-exposed regions. Specific agents may label reactive functional groups in amino acids, primarily cysteine, methionine, tyrosine, and tryptophan. Nonspecific radical intermediates (reactive oxygen, nitrogen, or halogen species) can be produced by chemical, photochemical, electrochemical, or enzymatic methods. More targeted oxidation can be achieved by chemical reagents but also by direct electrochemical oxidation, which opens the way to instrumental labeling methods. Oxidative labeling of amino acids in the context of liquid chromatography(LC)–mass spectrometry (MS) based proteomics allows for differential LC separation, improved MS ionization, and label-specific fragmentation and detection. Oxidation of proteins can create new reactive groups which are useful for secondary, more conventional derivatization reactions with, e.g., fluorescent labels. This review summarizes reactions of oxidizing agents with peptides and proteins, the corresponding methodologies and instrumentation, and the major, innovative applications of oxidative protein labeling described in selected literature from the last decade

Glomerular filtration rate-estimating equations for patients with advanced chronic kidney disease

Renal function is often estimated using one of several glomerular filtration rate (GFR) estimating equations. However, there is no consensus which estimating equation performs best in patients with advanced renal failure. We compared the performance of five different estimated GFR (eGFR) equations [Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease (CKD) Epidemiology collaboration (CKD-EPI) and Mayo Clinic and Lund-Malm] with measured GFR (plasma iohexol clearance) in 2098 referred CKD patients with mGFR 30 mL/min/1.73 m(2). There were 398 patients with an mGFR 10 mL/min/1.73 m(2), 1974 with a measured GFR (mGFR) 1120 mL/min/1.73 m(2) and 749 patients with mGFR 2130 mL/min/1.73 m(2). Across the entire range, the median bias of eGFR was lowest for the Lund-Malm equation (0.7 mL/min/1.73 m(2)), followed by the CKD-EPI (1.2 mL/min/1.73 m(2)), the MDRD (1.6 mL/min/1.73 m(2)), Mayo Clinic equation (1.7 mL/min/1.73 m(2)) and Cockcroft-Gault equation (4.6 mL/min/1.73 m(2)). The best accuracy within 30 of mGFR was also for Lund-Malm (76), while it was similar for CKD-EPI, MDRD and Mayo (6567). The Cockcroft-Gault had the worst accuracy of only 54.The median bias was stable across mGFR categories, while the accuracy within 30 of mGFR became worse with decreasing mGFR. All equations performed best among patients with hereditary kidney diseases and tubulointerstitial disease. Accuracy was generally worse for patients 65 years of age and for those with diabetic nephropathy. In patients with advanced renal failure, the GFR-estimating equations show reasonably good performance on the population level. On the individual patient level, they are inaccurate, especially in elderly patients and those with diabetic nephropathy

Incidence and risk factors for hip or other bone fractures among hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study.

The available data on bone fractures in hemodialysis (HD) patients are limited to results of a few studies of subgroups of patients in the United States. This study describes the prevalence of hip fractures and the incidence and risk factors associated with hip and other fractures in representative groups of HD facilities (n=320) and patients (n=12 782) from the 12 countries in the second phase of the Dialysis Outcomes and Practice Patterns Study (2002-2004). Among prevalent patients, 2.6% had a prior hip fracture. The incidence of fractures was 8.9 per 1000 patient years for new hip fractures and 25.6 per 1000 for any new fracture. Older age (relative risk (RR)(HIP)=1.91, RR(ANY)=1.33, P900 pg/ml were associated with an elevated risk of any new fracture (RR=1.72, P<0.05) versus PTH 150-300. The results suggest that greater selectivity in prescribing several classes of psychoactive drugs and more efficient treatment of secondary hyperparathyroidism may help reduce the burden of fractures in HD patients