Plasma Concentrations of Myeloperoxidase Predict Mortality After Myocardial Infarction

ObjectivesThis study investigated relationships between plasma myeloperoxidase (MPO), protein oxidation markers, and clinical outcome retrospectively in patients after acute myocardial infarction (MI).BackgroundReactive oxidants are implicated in cardiovascular disease, and elevated plasma MPO is reported to predict adverse outcome in acute coronary syndromes.MethodsDetailed demographic information, radionuclide ventriculography, neurohormone measurements, and clinical history were obtained for 512 acute MI patients at hospital admission. Plasma levels of MPO and protein carbonyls were measured in patients and 156 heart-healthy control subjects. 3-Chlorotyrosine was measured in selected patients. Patient mortality was followed for 5 years.ResultsPlasma MPO and protein carbonyl concentrations were higher in MI patients 24 h to 96 h after admission than in control subjects (medians: MPO 55 ng/ml vs. 39 ng/ml, and protein carbonyls 48 pmol/mg vs. 17 pmol/mg protein, p < 0.001 for each). Both markers were significantly correlated with each other and with cardiovascular hormone levels. Chlorotyrosine was not elevated in patients with high MPO or carbonyl levels. Above-median levels of MPO but not protein carbonyls were independently predictive of mortality (odds ratio 1.8, 95% confidence interval 1.0 to 3.0, p = 0.034). Patients with above-median MPO levels in combination with above-median plasma amino-terminal pro-brain natriuretic peptide (NT-proBNP) or below-median left ventricular ejection fraction (LVEF) had significantly greater mortality compared with other patients.ConclusionsMyeloperoxidase and protein carbonyl levels are elevated in plasma after acute MI, apparently via independent mechanisms. High MPO is a risk factor for long-term mortality and adds prognostic value to LVEF and plasma NT-proBNP measurements

Myeloperoxidase and oxidative stress in rheumatoid arthritis

Objective. To determine whether MPO contributes to oxidative stress and disease activity in RA and whether it produces hypochlorous acid in SF. Methods. Plasma and where possible SF were collected from 77 RA patients while 120 healthy controls supplied plasma only. MPO and protein carbonyls were measured by ELISAs. 3-Chlorotyrosine in proteins and allantoin in plasma were measured by mass spectrometry. Results. Plasma MPO concentrations were significantly higher in patients with RA compared with healthy controls [10.8 ng/ml, inter-quartile range (IQR): 7.214.2; P < 0.05], but there was no significant difference in plasma MPO protein concentrations between RA patients with high disease activity (HDA; DAS-28 >3.2) and those with low disease activity (LDA; DAS-28 43.2) (HDA 27.9 ng/ml, 20.234.1 vs LDA 22.1 ng/ml, 16.934.9; P > 0.05). There was a significant relationship between plasma MPO and DAS-28 (r = 0.35; P = 0.005). Plasma protein carbonyls and allantoin were significantly higher in patients with RA compared with the healthy controls. MPO protein was significantly higher in SF compared with plasma (median 624.0 ng/ml, IQR 258.42433.0 vs 30.2 ng/ml, IQR 25.150.9; P < 0.0001). The MPO present in SF was mostly active. 3-Chlorotyrosine, a specific biomarker of hypochlorous acid, was present in proteins from SF and related to the concentration of MPO (r = 0.69; P = 0.001). Protein carbonyls in SF were associated with MPO protein concentration (r = 0.40; P = 0.019) and 3-chlorotyrosine (r = 0.66; P = 0.003). Conclusion. MPO is elevated in patients with RA and promotes oxidative stress through the production of hypochlorous acid

The role of human alpha-2-macroglobulin in health and disease

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Breath Ammonia Reduction Ratio (ARR) Measures Dialysis Efficacy

Contemporary evidence supports the centuries old notion that expired breath and the headspaces above body fluids and products can serve as biomarkers of organ function. Clinical responsiveness to alterations in clinical status or therapy is dependent upon timely, accurate, relevant physiological data. Current measures of urea and creatinine to assess renal urea reduction are invasive and cannot be repeated frequently or reported quickly enough to define individual response to treatment in real time. In contrast, breath analysis is minimally invasive and can provide real time information about low molecular weight volatile organic compounds (VOCs) such as ammonia1,2

Classification Algorithms for SIFT-MS Medical Diagnosis

Selected Ion Flow Tube - Mass Spectrometry (SIFTMS) is an analytical technique for the real-time quantification of trace gases in air or breath samples. The SIFT-MS system can potentially offer unique capability in the early and rapid detection of a wide variety of diseases, infectious bacteria and patient conditions, by using a classifier to differentiate between control and test groups. By identifying which masses and Volatile Organic Compounds (VOCs) contribute most strongly towards a successful classification, biomarkers for a particular disease state may be discovered. A classification method is presented and validated in a simple study in which saturated nitrogen in tedlar bags was differentiated from dry nitrogen in tedlar bags. Several biomarkers were identified, with the most reliable being N2H+.H2O, and isotopes and water clusters of H3O+, as expected. The classifier was then applied in a clinical setting to differentiate between patient breath samples after one and four hours of dialysis treatment. Biomarkers for classification were ammonia, acetaldehyde, ethanol, isoprene and acetone. The model classifies significantly better than random, with an ROC area of 0.89

Disease stage-dependent accumulation of lipid and protein oxidation products in human atherosclerosis

Oxidative modification of low-density lipoprotein is thought to promote arterial lipid accumulation and atherogenesis. Previous studies reported on the presence of certain lipid or protein oxidation products in lesions, although a systematic investigation measuring several oxidation parameters and the accumulation of nonoxidized lipids and antioxidants at various stages of atherosclerosis has not been performed in the same tissue. Using the intimal lipoprotein-containing fraction of human aortic lesions, we demonstrate here that cholesterol accumulated with lesion development and that this increase was already significant at the fatty streak stage. By comparison, cholesterylesters increased significantly only in fibrofatty and more complex lesions that also contained significantly increased amounts of cholesterylester hydro(pero)xides and 27-hydroxycholesterol. Cholesterylester hydroxides were the major lipid oxidation product detected. Despite accumulation of oxidized lipid, α-tocopherol was also present and maintained at a comparable level over the disease process. Of the oxidized protein moieties measured only o,o-dityrosine increased with disease, although chlorotyrosines were present at relatively high levels in all lesions compared to healthy vessels. Our data show that accumulation of nonoxidized lipid precedes that of oxidized lipid in human aortic lesions