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1.
Rev Med Interne ; 42(2): 110-119, 2021 Feb.
Article in French | MEDLINE | ID: mdl-33172708

ABSTRACT

Fabry disease is the second most frequent lysosomal storage disorder. It is a X-linked genetic disease secondary to alpha-galactosidase A enzyme deficiency. This is a progressive and systemic disease that affects both males and females. Classical symptoms and organ involvements are acral pain crisis, cornea verticillata, hypertrophic cardiomyopathy, stroke and chronic kidney disease with proteinuria. Nevertheless, organ damages can be missing or pauci-symptomatic and other common symptoms are poorly recognised, such as gastrointestinal or ear involvement. In classical Fabry disease, symptoms first appear during childhood or teenage in males, but later in females. Patients may have non-classical or late-onset Fabry disease with delayed manifestations or with single-organ involvement. Recognition of Fabry disease is important because treatments are available, but it may be challenging. Diagnosis is easy in males, with dosage of alpha-galactosidase A enzyme activity into leukocytes, but more difficult in females who can express normal residual activity. Other plasmatic biomarkers, such as lyso-globotriaosylceramide (lyso-Gb3), are interesting in females, but need to be associated with GLA gene analysis. In this review, we aimed at summarize the main clinical manifestations of Fabry disease and propose a practical algorithm to know how to diagnose this complex disease.


Subject(s)
Fabry Disease , Stroke , Adolescent , Biomarkers , Disease Progression , Fabry Disease/complications , Fabry Disease/diagnosis , Fabry Disease/epidemiology , Female , Humans , Male , alpha-Galactosidase/genetics
2.
Faraday Discuss ; 187: 521-37, 2016 06 23.
Article in English | MEDLINE | ID: mdl-27048927

ABSTRACT

Several proof-of-concept studies on the vibrational spectroscopy of biofluids have demonstrated that the methodology has promising potential as a clinical diagnostic tool. However, these studies also show that there is a lack of a standardised protocol in sample handling and preparation prior to spectroscopic analysis. One of the most important sources of analytical errors is the pre-analytical phase. For the technique to be translated into clinics, it is clear that a very strict protocol needs to be established for such biological samples. This study focuses on some of the aspects of the pre-analytical phase in the development of the high-throughput Fourier Transform Infrared (FTIR) spectroscopy of some of the most common biofluids such as serum, plasma and bile. Pre-analytical considerations that can impact either the samples (solvents, anti-coagulants, freeze-thaw cycles…) and/or spectroscopic analysis (sample preparation such as drying, deposit methods, volumes, substrates, operators dependence…) and consequently the quality and the reproducibility of spectral data will be discussed in this report.


Subject(s)
Analytic Sample Preparation Methods/methods , Analytic Sample Preparation Methods/standards , Body Fluids/chemistry , Body Fluids/diagnostic imaging , Spectroscopy, Fourier Transform Infrared/methods , Spectroscopy, Fourier Transform Infrared/standards , Anticoagulants/chemistry , Bile/chemistry , Freezing , Humans , Plasma/chemistry , Reproducibility of Results , Serum/chemistry , Solvents/chemistry , Vibration
3.
JIMD Rep ; 9: 93-96, 2013.
Article in English | MEDLINE | ID: mdl-23430553

ABSTRACT

Sarcosinemia is a rare inborn error of metabolism that is characterised by an increased level of sarcosine (N-methylglycine) in the plasma and urine. The enzymatic block results from a deficiency of sarcosine dehydrogenase (SarDH), a liver mitochondrial matrix enzyme that converts sarcosine into glycine. Although this condition may remain inapparent until later life, it has been reported in rare cases to lead to neurodevelopmental disability. A 19-year-old male with sarcosinemia presented with dystonia, developmental delay and cognitive impairment. Magnetic resonance imaging revealed vermian hypotrophy. A 2-year pharmacological treatment with memantine was negative on the clinical signs. In this case, it was concluded that the metabolic block leading to sarcosinemia was responsible of a pathologic condition with mental deficiency and complex neurological signs. A maternal isodisomy discovered in the vicinity of SarDH gene could contribute to this pathology. Deficit of SarDH may be considered as a differential diagnosis of growth failure during prenatal stages and respiratory failure at birth following a slowly progressive developmental delay.

4.
Arch Pediatr ; 19(2): 184-93, 2012 Feb.
Article in French | MEDLINE | ID: mdl-22244319

ABSTRACT

MCAD deficiency is the most common fatty acid oxidation disorder, with the prevalence varying from 1/10,000 to 1/27,000 in the countries adjacent to France. As the High Authority for Health has recently proposed including MCAD deficiency in the panel of diseases neonatally screened for in France, a consensus was written for the management of MCAD deficiency diagnosed either clinically or by neonatal screening. Patients may present acutely with hyperammonemia, hypoglycemia, encephalopathy, and hepatomegaly, mainly after a prolonged fast of intercurrent infection. Sudden death related to heartbeat disorders may also occur. The diagnosis of MCAD deficiency is suspected on the plasma acylcarnitine and/or the urinary organic acid profile. The diagnosis is confirmed by molecular biology and the enzymatic activity for patients who are not homozygous for the main mutation c.985A>G. However, some MCAD-deficient individuals may remain asymptomatic throughout life. The mainstay of treatment consists in avoiding prolonged fast and prescribing l-carnitine for patients who exhibit a deficiency in plasma carnitine. This management has radically modified the natural history of MCAD deficiency. This consensus will allow homogeneous management of these patients once the neonatal screening of MCAD deficiency has been introduced in France.


Subject(s)
Lipid Metabolism, Inborn Errors/diagnosis , Lipid Metabolism, Inborn Errors/therapy , Neonatal Screening , Acyl-CoA Dehydrogenase/deficiency , Decision Trees , France , Humans , Infant, Newborn , Lipid Metabolism, Inborn Errors/physiopathology
5.
J Thromb Haemost ; 6(9): 1586-94, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18541003

ABSTRACT

BACKGROUND: Tissue factor (TF), the main trigger of coagulation cascade, is a major component of the atherosclerotic plaque. Matrix metalloproteinases (MMPs) are recognized as key mediators of extracellular matrix remodeling during inflammation. It was recently emphasized that both TF and MMP-9 were overexpressed in atherosclerotic plaques, suggesting a role of both molecules in plaque instability and thrombogenicity. OBJECTIVE: The present study was designed to determine whether human monocytes could co-express TF and MMP-9 when the cells interact with type I collagen, a major component of the extracellular matrix and atherosclerotic plaque. METHODS: Human monocytes were isolated by elutriation and incubated in collagen I-coated plates. Tissue factor and MMP-9 expression were examined using real-time reverse transcription-polymerase chain reaction, flow cytometry, western blot and zymography. The activation of nuclear factor-kappa B (NF-kappaB) and the role of reactive oxygen species (ROS) in TF and MMP-9 production was studied using gel shift experiments, antioxidants pyrrolidine dithiocarbamate (PDTC) and N-acetyl-cysteine (NAC), and apocynin (a specific inhibitor of the NADPH oxidase). RESULTS: Type I collagen induced TF expression and increased MMP-9 production. In addition, the pro-inflammatory tumor necrosis factor-alpha (TNF-alpha), produced in response to collagen I, increased MMP-9 production. PDTC and NAC inhibited NF-kappaB activation during monocyte interaction with collagen I. Finally, both antioxidants and apocynin decreased the expression of TF, TNF-alpha, and MMP-9. CONCLUSIONS: These results indicate a new mechanism in the monocyte expression of TF and MMP-9 in response to collagen I involving a ROS-dependent pathway linked to the activation of the NADPH oxidase.


Subject(s)
Collagen Type I/physiology , Matrix Metalloproteinase 9/biosynthesis , Monocytes/metabolism , Thromboplastin/metabolism , Acetophenones/pharmacology , Acetylcysteine/pharmacology , Base Sequence , Blotting, Western , Cells, Cultured , Cytokines/physiology , DNA Primers , Electrophoretic Mobility Shift Assay , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Humans , Monocytes/enzymology , NF-kappa B/metabolism , Oxidation-Reduction , Pyrrolidines/pharmacology , Reactive Oxygen Species/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Thiocarbamates/pharmacology
6.
Ann Biol Clin (Paris) ; 65(6): 629-35, 2007.
Article in French | MEDLINE | ID: mdl-18039607

ABSTRACT

We have determined the concentration of Lp(a) in an Ivory Coast population (n=102) using two immunochemical methods: Laurell's monodimensional electro-immunodiffusion (EID) and immunonephelometry (IN). Within-run and between-run precision was respectively 3.07% and 3.97% by IN and 1.52% and 4.48% by EID method. As regard the exactitude, the bias goals in two methods were 3.5% and 3.0% respectively with IN and EID. The two methods were correlated (r=0.84; p=0.006). Mean values of Lp(a) were significantly (p=0.0007) higher by IN than EID: 0.48+/-0.34 g/L versus 0.32+/-0.19 g/L. The Lp(a) distributions were non-Gaussian, skewed towards high values, with median value of 0.47 g/L and 0.32 g/L respectively for IN and EID methods. Therefore, we conclude that although both methods showed a satisfactory precision, and results were correlated, Lp(a) values were higher by INP. Furthermore, mean values of Lp(a) in presumed healthy Ivorian is higher than in Caucasians.


Subject(s)
Immunoassay/methods , Lipoprotein(a)/blood , Adolescent , Adult , Cote d'Ivoire , Humans , Immunodiffusion , Middle Aged , Nephelometry and Turbidimetry , Reference Values , Reproducibility of Results , Sensitivity and Specificity
7.
Ann Biol Clin (Paris) ; 65(5): 545-9, 2007.
Article in French | MEDLINE | ID: mdl-17913674

ABSTRACT

Measurement of osmolality and calculation of osmolar gap are useful diagnostic tools in pathological situations such as hyponatremia, or intoxication by methanol or ethylene glycol. It is thus necessary to handle reliable systems of osmolality measurement. The aim of this study was to compare performances of two currently available osmometers, Fiske 210 and Advanced 3300 devices, both of them being distributed by Radiometer S.A.S. society, in order to determine the best criteria for purchase. This study showed very good performances of repeatability and reproductibility for both analyzers (CV< 2.1%) and a good correlation of results between them and with the osmometer routinely used in the laboratory. Other criteria such as a more suitable praticability for our needs and a better quality/price ratio orientated our choice towards Fiske 210 osmometer.


Subject(s)
Clinical Chemistry Tests/instrumentation , Clinical Laboratory Techniques/instrumentation , Blood Chemical Analysis/instrumentation , Blood Chemical Analysis/standards , Clinical Chemistry Tests/standards , Clinical Laboratory Techniques/standards , Equipment Design , Humans , Materials Testing , Osmolar Concentration , Reproducibility of Results , Urinalysis/instrumentation , Urinalysis/standards
8.
J Dent Res ; 85(8): 745-50, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16861293

ABSTRACT

Elastin peptides were previously reported to increase MMP expression in several cell types. We found binding of these peptides to their receptors led to enhanced MMP-3 and MMP-1 expression, but not activation, in human gingival fibroblasts cultured on plastic dishes. We hypothesized that these peptides, in a more physiological environment, might additionally trigger an MMP-3/MMP-1 activation cascade, leading to matrix lysis, as occurs in periodontitis. To test this hypothesis, we used contracted and attached lattices as gingival lamina propria equivalents. In such 3D models, supplementation of elastin peptides and plasminogen triggered an MMP-3/MMP-1 activation cascade and significant down-regulation of TIMPs production, further leading to intense collagen degradation. We propose that elastolysis, as occurs in periodontitis, potentiates collagenolysis, thus promoting disease progression.


Subject(s)
Elastin/metabolism , Fibrillar Collagens/metabolism , Gingiva/metabolism , Matrix Metalloproteinase 3/metabolism , Adult , Blotting, Western , Cell Culture Techniques , Cells, Cultured , Enzyme Activation , Fibroblasts/metabolism , Gingiva/cytology , Humans , Matrix Metalloproteinase 1/metabolism , Middle Aged , Models, Biological , Oligopeptides/metabolism , Plasminogen/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Tissue Inhibitor of Metalloproteinases/antagonists & inhibitors
11.
J Biomed Mater Res A ; 68(1): 114-22, 2004 Jan 01.
Article in English | MEDLINE | ID: mdl-14661256

ABSTRACT

Osteogenic properties of bone cells are a key parameter governing osseointegration of implant devices. In this context, osteoblasts have a central role via extracellular matrix synthesis and remodeling that they regulate through different protease activity. In this study, we have analyzed the expression of two matrix metalloproteinases (MMPs): MMP-2 (72 kDa) and MMP-9 (92 kDa) and their specific tissue inhibitors TIMP-1 and TIMP-2 in primary human osteoblastic cells. The effect of titanium, zirconia, and alumina ceramics on the synthesis of these proteases was assessed using reverse transcriptase-polymerase chain reaction, enzyme-linked immunosorbent assay, and zymographic analysis. Our results showed that osteoblasts express MMP-2 and -9 mRNA. Furthermore, MMP-2 mRNA expression was decreased by titanium and increased by alumina whereas zirconia did not have any significant effect. Conversely, MMP-9 mRNA expression was stimulated by titanium but decreased with zirconia, whereas alumina induced no significant changes. Zymographic analysis has evidenced pro-MMP-2 gelatinolytic activity in all cell populations with time-dependent increase profile; pro-MMP-9, however, was not detected. Enzyme-linked immunosorbent assay data confirmed the production of MMP-2 and very low levels of MMP-9. In addition, TIMP-1 was secreted in 24-h-cultured cells and increased to maximal level at 48-72 h whereas TIMP-2 levels were very low. The interactions between human osteoblasts and the studied biomaterials altered both MMP-2, -9 and TIMP-1expression indicating that biomaterials may influence osseointegration and bone remodeling.


Subject(s)
Aluminum Oxide/pharmacology , Ceramics/pharmacology , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 9/genetics , Osteoblasts/metabolism , Tissue Inhibitor of Metalloproteinase-1/genetics , Tissue Inhibitor of Metalloproteinase-2/genetics , Titanium/pharmacology , Zirconium/pharmacology , Base Sequence , DNA Primers , Enzyme-Linked Immunosorbent Assay , Humans , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Osteoblasts/drug effects , Osteoblasts/enzymology , Reverse Transcriptase Polymerase Chain Reaction , Tissue Inhibitor of Metalloproteinase-1/metabolism , Tissue Inhibitor of Metalloproteinase-2/metabolism
12.
Parasite ; 10(1): 59-64, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12669350

ABSTRACT

Host cell invasion is essential for the pathogenicity of the obligate intracellular protozoan parasite Toxoplasma gondii. In the present study, we evaluated the ability of T. gondii tachyzoites to trigger phosphorylation of the different mitogen-activated protein kinases (MAPK) in human monocytic cells THP1. Kinetic experiments show that the peak of extracellular-signal-regulated kinase (ERK1/2), P38 and cjun-NH2 terminal kinase (JNKs) phosphorylation occurs between 10 and 60 min. The use of specific inhibitors of ERK1/2, P38 and JNK1/2 phosphorylation indicates the specificity of MAPKs phosphorylation during invasion. Signaling through cellular and parasite mitogen-activated protein (MAP) kinase pathways appears to be critical for T. gondii invasion.


Subject(s)
JNK Mitogen-Activated Protein Kinases , MAP Kinase Signaling System , Mitogen-Activated Protein Kinases/metabolism , Toxoplasmosis/metabolism , Animals , Cells, Cultured , Enzyme Activation , Humans , MAP Kinase Kinase 4 , Mitogen-Activated Protein Kinase Kinases/metabolism , Phosphorylation , Toxoplasma , p38 Mitogen-Activated Protein Kinases
13.
Arch Mal Coeur Vaiss ; 95(9): 775-80, 2002 Sep.
Article in French | MEDLINE | ID: mdl-12407791

ABSTRACT

The biochemical markers of myocardial ischaemia have to be interpreted according to their kinetics; their interests depend on the clinical presentation. They are helpful to orient to a myocardial ischaemia in front of undefined chest pain, to stratify the outcome of acute coronary syndrome without ST segment elevation, to evaluate the amount of myocardial damage following infarction, to detect the failure of thrombolysis therapy and probably to stratify the post percutaneous coronary intervention outcome.


Subject(s)
Biomarkers/analysis , Myocardial Ischemia/diagnosis , Myocardium/pathology , Arrhythmias, Cardiac , Chest Pain , Fibrinolytic Agents/therapeutic use , Humans , Kinetics , Myocardial Ischemia/pathology , Necrosis , Risk Factors
14.
Exp Cell Res ; 271(1): 84-93, 2001 Nov 15.
Article in English | MEDLINE | ID: mdl-11697885

ABSTRACT

Metabolic functions of fibroblasts are tightly regulated by the extracellular environment. When cultivated in tridimensional collagen lattices, fibroblasts exhibit a lowered activity of protein synthesis, especially concerning extracellular matrix proteins. We have previously shown that extracellular collagen impaired the processing of ribosomal RNA (rRNA) in nucleoli by generating changes in the expression of nucleolar proteins and a premature degradation of neosynthesized rRNA. In this study, we have investigated whether inhibiting the synthesis of fibrillarin, a major nucleolar protein with decreased expression in collagen lattices, could mimic the effects of extracellular matrix. Monolayer-cultured fibroblasts were transfected with anti-fibrillarin antisense oligodeoxynucleotides, which significantly decreased fibrillarin content. Downregulation of fibrillarin expression inhibited procollagen secretion into the extracellular medium, without altering total collagen production. No changes of pro1(I)collagen mRNA expression or proline hydroxylation were found. A concomitant intracellular retention of collagen and its chaperone protein HSP47 was found, but no effect on the production of other extracellular matrix macromolecules or remodelling enzymes was observed. These data show that collagen processing depends on unknown mechanisms, involving proteins primarily located in the nucleolar compartment with other demonstrated functions, and suggest specific links between nucleolar machinery and extracellular matrix.


Subject(s)
Chromosomal Proteins, Non-Histone/metabolism , Collagen/metabolism , Nuclear Proteins/metabolism , Cells, Cultured , Chromosomal Proteins, Non-Histone/genetics , Down-Regulation , Extracellular Matrix Proteins/metabolism , Fibroblasts/cytology , Fibroblasts/metabolism , HSP47 Heat-Shock Proteins , Heat-Shock Proteins/metabolism , Humans , Immunohistochemistry , Oligodeoxyribonucleotides, Antisense/genetics , Oligodeoxyribonucleotides, Antisense/metabolism , Ribonucleoproteins/metabolism , Transfection
15.
Biochem J ; 350 Pt 3: 777-83, 2000 Sep 15.
Article in English | MEDLINE | ID: mdl-10970792

ABSTRACT

Glycation and glycoxidation processes, which are increased in diabetes mellitus, are generally considered causative mechanisms of long-term complications. With reference to our previous studies, type-I and -IV collagens could induce differentially the adhesion and stimulation of polymorphonuclear leucocytes (PMNs). As PMNs play a role in sustained diabetic oxidative stress, the present study was designed to determine whether in vitro glycoxidation of these macromolecules could alter PMN adhesion, activation and migration. The adhesion of PMNs to in vitro-glycoxidized collagens was significantly increased when compared with control collagens: +37% (P<0.05) and +99% (P<0.01) for collagens I and IV, respectively. Glycoxidized type-I collagen increased the chemotactic properties of PMNs without significant stimulatory effect on respiratory burst, whereas pre-incubation of PMNs with glycoxidized type-I collagen induced a priming on subsequent stimulation by N-formyl-methionyl-leucyl-phenylalanine. Glycoxidation of type-IV collagen suppressed its inhibitory effect on further PMN stimulation or migration. Collectively, these results indicate that glycoxidation of two major extracellular-matrix collagens considerably alters their ability to modulate PMN migration and production of reactive oxygen species. This imbalance in PMN metabolism may be a major event in the increased oxidative status that characterizes diabetes mellitus.


Subject(s)
Collagen/metabolism , Glucose/metabolism , Neutrophils/metabolism , Chemotaxis, Leukocyte , Humans , In Vitro Techniques , Neutrophil Activation , Neutrophils/cytology , Oxidation-Reduction
16.
J Immunol ; 164(11): 5928-34, 2000 Jun 01.
Article in English | MEDLINE | ID: mdl-10820275

ABSTRACT

Human blood monocytes are attracted into connective tissues during early steps of inflammation and wound healing, and locally interact with resident cells and extracellular matrix proteins. We studied the effects of type I collagen on monocyte adhesion and superoxide anion production, using human monocytes elutriated from peripheral blood and type I collagen obtained from rat tail tendon. Both acid-soluble and pepsin-digested type I collagens promoted the adhesion of monocytes, whereas only acid-soluble collagen with intact telopeptides induced the production of superoxide. Adhesion and activation of monocytes on acid-soluble type I collagen depended on the presence of divalent cations. mAbs directed against integrin subunits CD11c and CD18 specifically inhibited adhesion and activation of monocytes on type I collagen. Protein membrane extracts obtained from monocytes were submitted to affinity chromatography on collagen I-Sepharose 4B, and analyzed by Western blotting using specific anti-integrin subunit Abs. In the case of both acid-soluble and pepsin-digested collagens, two bands were revealed with mAbs against CD11c and CD18 integrin subunits. Our results demonstrate that monocytes interact with type I collagen through CD11c-CD18 (alpha x beta 2) integrins, which promote their adhesion and activation. For monocyte activation, specific domains of the type I collagen telopeptides are necessary. Interactions between monocytes and collagen are most likely involved in the cascade of events that characterize the initial phases of inflammation.


Subject(s)
CD11 Antigens/physiology , CD18 Antigens/physiology , Collagen/physiology , Membrane Glycoproteins/physiology , Monocytes/physiology , Acids , Animals , Antibodies, Monoclonal/pharmacology , Cations, Divalent/pharmacology , Cell Adhesion/drug effects , Cell Adhesion/immunology , Collagen/metabolism , Edetic Acid/pharmacology , Humans , Hydrogen-Ion Concentration , Integrin alphaXbeta2 , Kinetics , Monocytes/metabolism , Protein Denaturation , Rats , Rats, Sprague-Dawley , Solubility , Superoxides/antagonists & inhibitors , Superoxides/blood
17.
J Mal Vasc ; 25(5): 343-348, 2000 Dec.
Article in French | MEDLINE | ID: mdl-11148396

ABSTRACT

The interactions between leukocytes and endothelial cells have been studied extensively under conditions of ischemia and reperfusion. In contrast, attraction of leukocytes by platelets at the site of damage is poorly understood. This recruitment facilitates inflammation and atherogenesis. Studies performed ex vivo in coronary artery disease show that neutrophil-platelet adhesion increases in unstable angina, coronary angioplasty and coronary artery bypass surgery, in comparison with stable angina. Experimental works have shown the major role of platelet P-selectin in platelet-leukocyte interactions, and of fibrinogen, which is the ligand of both platelets and leukocytes (B2 integrins). Studied performed in anti-GPIIb/IIIa-treated patients demonstrate a modulation, as inhibition, of platelet-leukocyte interactions. This new drug inhibits platelet function and coagulation, and moreover inflammation.


Subject(s)
Blood Platelets/pathology , Chemotaxis, Leukocyte/drug effects , Coronary Disease/blood , Leukocytes/pathology , Platelet Adhesiveness/drug effects , Tyrosine/analogs & derivatives , Abciximab , Angina Pectoris/blood , Angina Pectoris/pathology , Angina, Unstable/blood , Angina, Unstable/pathology , Angioplasty, Balloon, Coronary , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/therapeutic use , Anticoagulants/pharmacology , Anticoagulants/therapeutic use , Aspirin/pharmacology , Aspirin/therapeutic use , Blood Platelets/drug effects , CD18 Antigens/physiology , Coronary Artery Bypass , Coronary Disease/pathology , Coronary Disease/surgery , Cytokines/physiology , Fibrinogen/physiology , Heparin/pharmacology , Heparin/therapeutic use , Humans , Immunoglobulin Fab Fragments/pharmacology , Immunoglobulin Fab Fragments/therapeutic use , Leukocytes/drug effects , Ligands , Macrophage-1 Antigen/physiology , Membrane Glycoproteins/physiology , Models, Biological , Myocardial Infarction/blood , Myocardial Infarction/drug therapy , Myocardial Infarction/pathology , Myocardial Infarction/surgery , Neutrophils/drug effects , Neutrophils/pathology , P-Selectin/physiology , Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation Inhibitors/therapeutic use , Platelet Glycoprotein GPIIb-IIIa Complex/antagonists & inhibitors , Platelet Glycoprotein GPIIb-IIIa Complex/physiology , Thrombospondins/physiology , Tirofiban , Tyrosine/pharmacology , Tyrosine/therapeutic use
18.
Thromb Haemost ; 82(1): 121-7, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10456465

ABSTRACT

In the present study we have investigated the effect of individual variations in the concentration of Lp(a) on plasmin formation at the surface of fibrin. The plasma Lp(a) concentrations from 20 nephrotic children were high at flare-up of the disease (0.43+/-0.45 g/l) and decreased progressively with remission at both 6 weeks (0.28+/-0.24 g/l) and 6 months (0.24+/-0.288 g/l). In contrast, the concentration of plasminogen showed an inverse variation, with low values at flare-up (1.27+/-0.34 microM) and normal values at remission (1.66+/-0.17 microM at 6 weeks and 1.99+/-0.21 microM at 6 months). An increase in plasmin formation (from 0.62+/-0.49 to 0.73+/-0.61, and 0.84+/-0.75 pmol/well) and a decrease in apo(a) binding (from 5.45+/-2.42 to 4.54+/-2.12, and 3.93+/-1.51 fmol/well) on the surface of fibrin, were concomitantly observed from flare-up to remission at 6 weeks and at 6 months, respectively. Values for plasmin formation parallel the amount of plasminogen bound. The low concentration of plasminogen found at flare-up may also have contributed to the increased binding of Lp(a) as indicated by a decrease in the maximal amount of Lp(a) bound (Bmax) to fibrin as a function of plasma plasminogen concentrations. Bmax was 1.51 fmol in the absence of plasminogen and decreased to 1.1 fmol and 0.93 fmol at respectively 1 and 2 microM of plasminogen. Altogether, these data constitute the first quantitative evidence indicating that plasmin formed at the surface of fibrin may vary with modifications of the concentration of Lp(a) in vivo.


Subject(s)
Fibrin/metabolism , Fibrinolysin/metabolism , Lipoprotein(a)/blood , Nephrotic Syndrome/blood , Adolescent , Child , Child, Preschool , Female , Genetic Variation , Humans , Infant , Lipoprotein(a)/genetics , Male
20.
Clin Chem Lab Med ; 36(5): 317-21, 1998 May.
Article in English | MEDLINE | ID: mdl-9676389

ABSTRACT

Lipoprotein(a) is a unique lipoprotein with atherothrombogenic properties. Although its blood concentration is mainly genetically determined, various factors exist which may cause variability. These may influence the clinical use of the results. We studied lipoprotein(a) biological variation by a rate nephelometric assay over a period of two years in a population of healthy fertile women. The study was performed in 12 volunteers, healthy subjects with various lipoprotein(a) concentrations, by monthly determinations during one year and a single determination one year later, together with measurements of total, high density lipoprotein and high density lipoprotein2 cholesterol, triglycerides and apolipoproteins A1 and B. The intra-individual variability of lipoprotein(a) ranged between 4 to 20%, with three subjects showing a coefficient of biological variation higher than 15%. In absolute terms, the difference between two determinations could represent 0.44 g/l or 50% of the mean value. This study suggests that physiological lipoprotein(a) variations should be taken into account for clinical purposes, especially in patients in need of thorough risk evaluation.


Subject(s)
Lipoprotein(a)/blood , Adult , Analysis of Variance , Arteriosclerosis/blood , Arteriosclerosis/etiology , Female , Fertility , Humans , Lipids/blood , Lipoprotein(a)/genetics , Middle Aged , Phenotype , Reference Values , Risk Factors , Thrombosis/blood , Thrombosis/etiology , Time Factors
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