Abstract:
:Despite many years of study, clinical trials of new drugs to prevent thrombosis have often been disappointing. Part of the problem lies in our incomplete understanding of the regulation of plasminogen activation and/or inhibition in vivo. We have previously shown that in vitro nitration of plasminogen in plasma by peroxynitrite resulted in decreased plasmin activity. We hypothesized that macrophages may be agents of plasminogen nitration and designed this study to prove this hypothesis. We first better characterized our previous observations using purified plasminogen instead of whole plasma, studied the time and concentration dependence of these reactions, and co-incubated plasminogen with macrophages, as well as with non-inflammatory cells as controls, to assess nitration and impaired activity. When plasminogen (10 micromol/L) is incubated in the presence of SIN-1 (0.01-2 mmol/L), plasmin activity (generated by streptokinase) is reduced in a time- and concentration-dependent fashion. We performed experiments incubating human plasminogen in the presence of murine RAW264.7 macrophages, allowing for free diffusion of reactive oxygen species, while preventing the action of proteases. In this way we show that incubation of plasminogen with macrophages also decreases plasmin activity, while increasing nitration of the molecule, an effect that is already apparent after 2 h and reaches a plateau of 60% inhibition after 24 h of incubation. This effect appears specific for macrophages, since 31EG4 murine mammary cells used in parallel and under the same conditions failed to produce any deleterious changes in plasminogen. Our data on quick functional inactivation of plasminogen by nitration, mediated by macrophages, adds a new pathophysiological dimension to our previous work showing plasminogen as a target for peroxynitrite damage. Nitrosative stress may be implicated in impaired fibrinolysis. New therapeutic approaches for nitrosative stress in atherosclerosis and diabetes should limit the formation of superoxides and peroxynitrite.
journal_name
Clin Chem Lab Medjournal_title
Clinical chemistry and laboratory medicineauthors
Hathuc C,Hermo R,Schulze J,Gugliucci Adoi
10.1515/CCLM.2006.039keywords:
subject
Has Abstractpub_date
2006-01-01 00:00:00pages
213-9issue
2eissn
1434-6621issn
1437-4331journal_volume
44pub_type
杂志文章abstract::The non-forage feeding of dairy cows rich in fast absorption carbohydrates, the low value of their euglycemic-hyperinsulinemic clamp suggest a dysregulation of carbohydrate metabolism able to produce neurodegenerative disorders. Comparisons between Alzheimer's disease developed in diabetes mellitus and bovine spongifo...
journal_title:Clinical chemistry and laboratory medicine
pub_type: 杂志文章
doi:10.1515/CCLM.2002.018
更新日期:2002-02-01 00:00:00
abstract::In blood, the exopeptidase dipeptidyl-peptidase IV (DPPIV; EC 3.4.14.5) is predominantly present in a soluble form in plasma/serum and as an activation antigen on the membrane of lymphocytes (CD26). It modifies some important biologically active peptides (neuropeptides, chemokines), and a regulatory role for DPPIV/CD2...
journal_title:Clinical chemistry and laboratory medicine
pub_type: 杂志文章
doi:10.1515/CCLM.2001.026
更新日期:2001-02-01 00:00:00
abstract::Background The relationship between renal disease and cardiovascular disease (CVD) is currently known as cardiorenal syndrome. Indoxyl sulfate (IS) is one of the uremic toxins that accelerates the progression of cardiorenal syndrome. This report presents a new method for measuring IS in a simpler way. Methods We evalu...
journal_title:Clinical chemistry and laboratory medicine
pub_type: 杂志文章
doi:10.1515/cclm-2019-0218
更新日期:2019-10-25 00:00:00
abstract::The clinical usefulness of C-reactive protein (CRP) and of transthyretin (TTR) for the early diagnosis and follow-up of infection after an open fracture was prospectively investigated (cohort A). It was complemented by a retrospective study of trauma patients admitted to an intensive care unit (cohort B). Serial deter...
journal_title:Clinical chemistry and laboratory medicine
pub_type: 杂志文章
doi:10.1515/CCLM.2002.230
更新日期:2002-12-01 00:00:00
abstract::Human protein 1/Clara cell Mr 10,000 protein consists of two identical subunits of seventy amino acid residues each. In the present study, eight clones of monoclonal antibodies against native protein 1 were prepared and their respective epitopes were immunochemically and immunohistochemically characterized using nativ...
journal_title:Clinical chemistry and laboratory medicine
pub_type: 杂志文章
doi:10.1515/CCLM.1999.098
更新日期:1999-06-01 00:00:00
abstract:BACKGROUND:Detection of systemic sclerosis-associated autoantibodies (SSc-Ab) is mostly restricted to anti-centromere and anti-topoisomerase-I. However, anti-RNA-polymerase-III and anti-PM/Scl are also important diagnostic markers for the disease supporting their incorporation in the laboratory repertoire. The aim of t...
journal_title:Clinical chemistry and laboratory medicine
pub_type: 杂志文章
doi:10.1515/cclm-2013-0211
更新日期:2013-11-01 00:00:00
abstract::Background Monitoring of immunosuppressive drugs such as everolimus and sirolimus is important in allograft rejection prevention in transplant patients. Dried blood spots (DBS) sampling gives patients the opportunity to sample a drop of blood from a fingerprick at home, which can be sent to the laboratory by mail. Met...
journal_title:Clinical chemistry and laboratory medicine
pub_type: 杂志文章
doi:10.1515/cclm-2019-0053
更新日期:2019-11-26 00:00:00
abstract::Winning a Nobel Prize is a great personal achievement. Some Nobel laureates may consider that their award is a certificate of competence in any field. This may prompt them to undertake projects or accept positions which are beyond their capabilities. Since Nobels are awarded when the laureates have usually passed thei...
journal_title:Clinical chemistry and laboratory medicine
pub_type: 杂志文章
doi:10.1515/cclm-2013-0273
更新日期:2013-08-01 00:00:00
abstract::For several years it has been possible to routinely detect numerous mutations in the human genome by different methods. The most common technique is a standard PCR, but real time fluorescence PCR is increasingly being used. The purpose of this paper is to compare these two different techniques from the point of view o...
journal_title:Clinical chemistry and laboratory medicine
pub_type: 杂志文章
doi:10.1515/CCLM.2003.072
更新日期:2003-04-01 00:00:00
abstract::Most studies of the relation between psychological performance in the elderly and deficiencies of cobalamin and folate have used methods that determine the blood concentrations of these vitamins, which might not reflect the vitamin status in the tissues. Recently, two new markers, plasma homocysteine and methylmalonic...
journal_title:Clinical chemistry and laboratory medicine
pub_type: 杂志文章
doi:10.1515/CCLM.1999.142
更新日期:1999-10-01 00:00:00
abstract::There is some evidence from recent observational studies that hyperhomocysteinemia is a risk factor for cognitive dysfunction, including Alzheimer's disease and vascular dementia. There are only a few intervention studies, and the results are disappointing for such a frequent disease. Prospective double-blind and plac...
journal_title:Clinical chemistry and laboratory medicine
pub_type: 杂志文章,评审
doi:10.1515/CCLM.2001.119
更新日期:2001-08-01 00:00:00
abstract::The effect of solvent conditions on the aggregation of IgM in serum specimens from patients with macroglobulinemia was studied by a turbidimetric procedure. Aggregation of IgM varied considerably among the samples and was affected by a number of experimental parameters. In general, IgM aggregation was more pronounced ...
journal_title:Clinical chemistry and laboratory medicine
pub_type: 杂志文章
doi:10.1515/CCLM.2000.108
更新日期:2000-08-01 00:00:00
abstract::The etiology of cardiovascular diseases is known to be multi-factorial. Some forms of cardiovascular disease are influenced by unclear genetic factors but are predominantly affected by factors such as diet, obesity, cigarette smoking, diabetes mellitus and dyslipidaemia. Some are caused by specific gene defects, with ...
journal_title:Clinical chemistry and laboratory medicine
pub_type: 杂志文章,评审
doi:10.1515/CCLM.1998.106
更新日期:1998-08-01 00:00:00
abstract:BACKGROUND:Cardiac troponins currently represent the preferred biomarkers for the detection of myocardial necrosis. The objective of the present study was to compare the performance of the Access AccuTnl assay (Beckman Coulter) measured on two different platforms, the UniCel Dxl 800 and the Access 2 (Beckman Coulter). ...
journal_title:Clinical chemistry and laboratory medicine
pub_type: 杂志文章
doi:10.1515/cclm.2009.080
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:The timely detection of severe inflammatory conditions is of great importance for early therapy initiation and the patient's prognosis. The complex humoral and cellular processes involved in inflammation offer many opportunities for diagnostic testing, which are still unused in clinical practice. We investig...
journal_title:Clinical chemistry and laboratory medicine
pub_type: 杂志文章
doi:10.1515/cclm-2014-0482
更新日期:2015-03-01 00:00:00
abstract:BACKGROUND:Interpretation of alkaline phosphatase activity in children is challenging due to extensive changes with growth and puberty leading to distinct sex- and age-specific dynamics. Continuous percentile charts from birth to adulthood allow accurate consideration of these dynamics and seem reasonable for an analyt...
journal_title:Clinical chemistry and laboratory medicine
pub_type: 杂志文章
doi:10.1515/cclm-2016-0318
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:Recent studies show that platelets have important roles in the immune system. Little is known about the clinical significance of platelet indices. Changes in platelet indices, including platelet distribution width (PDW), mean platelet volume (MPV) and plateletcrit, in pulmonary tuberculosis were investigated...
journal_title:Clinical chemistry and laboratory medicine
pub_type: 杂志文章
doi:10.1515/CCLM.2007.194
更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:Tests for fecal calprotectin are usually either enzyme-linked immunosorbent assays (ELISA) or a time-resolved fluorimetric immunoassay (TRFIA). These time-consuming tests are performed only once every 1 or 2 weeks. Before the results of the tests are known most patients have already undergone colonoscopy. A ...
journal_title:Clinical chemistry and laboratory medicine
pub_type: 杂志文章
doi:10.1515/cclm-2011-0855
更新日期:2012-01-13 00:00:00
abstract:BACKGROUND:The clinical relevance of chromogranin A (CgA) concentrations depends on the analytical performance of the assay. The goal of the present study was to define the clinical involvements in CgA calibration models by evaluating the confidence intervals (CIs) for values from patients who were undergoing monitorin...
journal_title:Clinical chemistry and laboratory medicine
pub_type: 杂志文章
doi:10.1515/CCLM.2009.278
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:High-dose biotin therapy is beneficial in progressive multiple sclerosis (MS) and is expected to be adopted by a large number of patients. Biotin therapy leads to analytical interference in many immunoassays that utilize streptavidin-biotin capture techniques, yielding skewed results that can mimic various e...
journal_title:Clinical chemistry and laboratory medicine
pub_type: 杂志文章
doi:10.1515/cclm-2016-1183
更新日期:2017-05-01 00:00:00
abstract:BACKGROUND:The differential diagnosis between bacterial and viral meningitis is not easy in some cases. Cerebrospinal fluid (CSF) analysis is essential for establishing this diagnosis. The objectives were to quantitate lactic acid (LA) concentrations in bacterial and viral meningitis, and other central nervous system (...
journal_title:Clinical chemistry and laboratory medicine
pub_type: 杂志文章
doi:10.1515/CCLM.2009.160
更新日期:2009-01-01 00:00:00
abstract::Acute intestinal ischemic injury (i3) is a life-threatening condition with disastrous prognosis, which is currently difficult to diagnose at the early stages of the disease; a rapid diagnosis is mandatory to avoid irreversible ischemia, extensive bowel resection, sepsis and death. The overlapping protein expression of...
journal_title:Clinical chemistry and laboratory medicine
pub_type: 杂志文章,评审
doi:10.1515/cclm-2017-0291
更新日期:2018-02-23 00:00:00
abstract::Portable meters for blood glucose concentrations are used at the patients bedside, as well as by patients for self-monitoring of blood glucose. Even though most devices have important technological advances that decrease operator error, the analytical goals proposed for the performance of glucose meters have been rece...
journal_title:Clinical chemistry and laboratory medicine
pub_type: 杂志文章
doi:10.1515/CCLM.2005.147
更新日期:2005-01-01 00:00:00
abstract::The aim of this study was to clarify the effects of anti-dsDNA antibodies on the titer and the nuclear staining pattern(s) in a fluorescent antinuclear antibody (FANA) assay using HEp-2 cells. Anti-dsDNA derived from 14 patients with systemic lupus erythematosus (SLE) was individually affinity-purified. The anti-dsDNA...
journal_title:Clinical chemistry and laboratory medicine
pub_type: 杂志文章
doi:10.1515/CCLM.2002.009
更新日期:2002-01-01 00:00:00
abstract:BACKGROUND:Autoantibodies against β1-adrenergic receptors (β1AR) that stimulate cardiac cAMP-production play a causal role in the pathogenesis of human heart failure. Patients can be subjected to specific therapies, if the presence of potentially cardio-noxious β1AR-autoantibodies is reliably diagnosed. This requires a...
journal_title:Clinical chemistry and laboratory medicine
pub_type: 杂志文章
doi:10.1515/cclm-2015-0603
更新日期:2016-04-01 00:00:00
abstract::A questionable scientific approach to measuring at low concentrations and inappropriate censoring of results below certain cut-offs have resulted in the dichotomous classification of troponin assays based on their so-called analytical sensitivity. The definition of "high-sensitivity" cardiac troponin is flawed. Eviden...
journal_title:Clinical chemistry and laboratory medicine
pub_type: 杂志文章
doi:10.1515/cclm-2017-0025
更新日期:2017-10-26 00:00:00
abstract::Folate measurements, particularly for whole blood, show wide inter-laboratory and inter-methodology variability. This variability appears to be due in part to the lack of internationally accepted reference materials. A whole blood haemolysate, lyophilised in ampoules and designated 95/528, was therefore evaluated by 1...
journal_title:Clinical chemistry and laboratory medicine
pub_type: 杂志文章
doi:10.1515/CCLM.2004.090
更新日期:2004-05-01 00:00:00
abstract::Diabesity, that is to say, obesity-dependent diabetes, has emerged as a major public health problem. Though diabesity is basically explained by insulin resistance and pancreatic beta cell dysfunction, new paradigms have evolved to explain these alterations in the context of the modern epidemics of obesity and diabetes...
journal_title:Clinical chemistry and laboratory medicine
pub_type: 杂志文章,评审
doi:10.1515/CCLM.2003.174
更新日期:2003-09-01 00:00:00
abstract:BACKGROUND:Low back pain (LBP) is a very frequent condition, affecting most people at some point throughout their life. This cross-sectional study was aimed to investigate a selected panel of cytokines and inflammatory biomarkers in patients with or without LBP. METHODS:The study population consisted of 104 patients d...
journal_title:Clinical chemistry and laboratory medicine
pub_type: 杂志文章
doi:10.1515/cclm-2016-0942
更新日期:2017-08-28 00:00:00
abstract:BACKGROUND:The Schwartz 2009 creatinine-based revised formula is the only pediatric GFR estimating formula, which is compatible with the recent global creatinine standardization. This formula is only applicable if enzymatic creatinine methods are used. We propose an equation, taking into account the relative bias cause...
journal_title:Clinical chemistry and laboratory medicine
pub_type: 杂志文章
doi:10.1515/cclm-2012-0033
更新日期:2012-03-09 00:00:00