13 results on '"K.-H. Le Quan Sang"'
Search Results
2. Inflammatory and oxidative stress biomarkers in alkaptonuria: data from the DevelopAKUre project
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James A. Gallagher, M. Margollicci, Giulia Bernardini, Daniela Giustarini, Ranieri Rossi, Lia Millucci, Jozef Rovensky, Mohammed Alsbou, L. Peruzzi, Annalisa Santucci, Lakshminarayan R. Ranganath, Daniela Braconi, K.-H. Le Quan Sang, Richard Imrich, and Barbara Marzocchi
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Adult ,Male ,Serum ,0301 basic medicine ,medicine.medical_specialty ,Interleukin-1beta ,Amyloidosis ,Biomarker ,Chitotriosidase ,Protein thiols ,Serum amyloid A ,Rheumatology ,Biomedical Engineering ,Orthopedics and Sports Medicine ,Cathepsin D ,Inflammation ,Alkaptonuria ,medicine.disease_cause ,Young Adult ,03 medical and health sciences ,Internal medicine ,Humans ,Medicine ,Sulfhydryl Compounds ,Serum Amyloid A Protein ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,business.industry ,Middle Aged ,Oxidative Stress ,C-Reactive Protein ,Hexosaminidases ,030104 developmental biology ,Endocrinology ,Advanced Oxidation Protein Products ,Advanced oxidation protein products ,Biomarker (medicine) ,Female ,Matrix Metalloproteinase 3 ,Tumor necrosis factor alpha ,medicine.symptom ,business ,Biomarkers ,Oxidative stress - Abstract
Summary Objective The aim of this work was to assess baseline serum levels of established biomarkers related to inflammation and oxidative stress in samples from alkaptonuric subjects enrolled in SONIA1 (n = 40) and SONIA2 (n = 138) clinical trials (DevelopAKUre project). Methods Baseline serum levels of Serum Amyloid A (SAA), IL-6, IL-1β, TNFα, CRP, cathepsin D (CATD), IL-1ra, and MMP-3 were determined through commercial ELISA assays. Chitotriosidase activity was assessed through a fluorimetric method. Advanced Oxidation Protein Products (AOPP) were determined by spectrophotometry. Thiols, S-thiolated proteins and Protein Thiolation Index (PTI) were determined by spectrophotometry and HPLC. Patients' quality of life was assessed through validated questionnaires. Results We found that SAA serum levels were significantly increased compared to reference threshold in 57.5% and 86% of SONIA1 and SONIA2 samples, respectively. Similarly, chitotriosidase activity was above the reference threshold in half of SONIA2 samples, whereas CRP levels were increased only in a minority of samples. CATD, IL-1β, IL-6, TNFα, MMP-3, AOPP, thiols, S-thiolated protein and PTI showed no statistically significant differences from control population. We provided evidence that alkaptonuric patients presenting with significantly higher SAA, chitotriosidase activity and PTI reported more often a decreased quality of life. This suggests that worsening of symptoms in alkaptonuria (AKU) is paralleled by increased inflammation and oxidative stress, which might play a role in disease progression. Conclusions Monitoring of SAA may be suggested in AKU to evaluate inflammation. Though further evidence is needed, SAA, chitotriosidase activity and PTI might be proposed as disease activity markers in AKU.
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- 2018
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3. Perinatal and infantile hypophosphatasia: clinical features and treatment
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K.-H. Le Quan Sang, Geneviève Baujat, Valérie Cormier-Daire, and Caroline Michot
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0301 basic medicine ,Pediatrics ,medicine.medical_specialty ,Muscle Hypotonia ,Hypophosphatasia ,Disease ,030105 genetics & heredity ,Craniosynostosis ,03 medical and health sciences ,Hyperphosphatemia ,Risk Factors ,Seizures ,medicine ,Humans ,Enzyme Replacement Therapy ,Respiratory tract infections ,business.industry ,Infant, Newborn ,Infant ,Enzyme replacement therapy ,medicine.disease ,Alkaline Phosphatase ,Hypotonia ,Perinatal Care ,Treatment Outcome ,Pediatrics, Perinatology and Child Health ,Hypercalcemia ,medicine.symptom ,business ,Respiratory Insufficiency ,Biomarkers ,Follow-Up Studies - Abstract
Hypophosphatasia (HPP) is a rare hereditary disease characterized by defective skeletal mineralization, and with a broad severity spectrum. The perinatal forms, lethal and non-lethal, are associated with severe neonatal respiratory distress, potential seizures, hypotrophy and marked hypotonia. The diagnosis is rapidly suggested by a combination of typical radiological signs, hypercalcemia, hyperphosphatemia and low alkaline phosphatase (ALP) activity. In the infantile form, the clinical signs appear before the age of six months, but the patients usually have no or very mild signs at birth. The diagnosis should be considered in the event of early deformation of the pectus, feeding difficulties, hypotonia, frequent respiratory tract infections, hypercalcemia, and even early constitution of craniosynostosis. Radiological signs may be less obvious characterized by irregular metaphyses and generalized hypomineralization. Management is initially symptomatic, and adjusted to the symptoms. Care should be provided by a multidisciplinary team, in close collaboration with Reference Centers experts for the disease. Currently, recombinant enzyme replacement therapy (ERT) is under development for the severe form of HPP. The course of the disease, depending on the degree of severity and the various types of management, requires long-term evaluation through joint prospective follow-up to assess the long-term outcomes of these patients. Multidisciplinary follow up is needed to identify the medical and socio-economic outcomes of children and adults affected by HPP.
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- 2018
4. Ketone Bodies as a Possible Adjuvant to Ketogenic Diet in PDHc Deficiency but Not in GLUT1 Deficiency
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Nadia Bahi-Buisson, Clément Pontoizeau, P. de Lonlay, A. Boutron, Florence Habarou, Agathe Roubertie, Christine Broissand, Chris Ottolenghi, Marie-Thérèse Abi-Wardé, K. H. Le Quan Sang, Elise Lebigot, Sandrine Vuillaumier-Barrot, and Anaïs Brassier
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0301 basic medicine ,medicine.medical_specialty ,endocrine system ,Deficiency syndrome ,medicine.medical_treatment ,Article ,03 medical and health sciences ,0302 clinical medicine ,First line therapy ,Internal medicine ,medicine ,biology ,business.industry ,nutritional and metabolic diseases ,medicine.disease ,Pyruvate dehydrogenase deficiency ,carbohydrates (lipids) ,030104 developmental biology ,Endocrinology ,biology.protein ,Ketone bodies ,GLUT1 ,business ,Adjuvant ,030217 neurology & neurosurgery ,Intractable seizures ,hormones, hormone substitutes, and hormone antagonists ,Ketogenic diet - Abstract
Ketogenic diet is the first line therapy for neurological symptoms associated with pyruvate dehydrogenase deficiency (PDHD) and intractable seizures in a number of disorders, including GLUT1 deficiency syndrome (GLUT1-DS). Because high-fat diet raises serious compliance issues, we investigated if oral L,D-3-hydroxybutyrate administration could be as effective as ketogenic diet in PDHD and GLUT1-DS.We designed a partial or total progressive substitution of KD with L,D-3-hydroxybutyrate in three GLUT1-DS and two PDHD patients.In GLUT1-DS patients, we observed clinical deterioration including increased frequency of seizures and myoclonus. In parallel, ketone bodies in CSF decreased after introducing 3-hydroxybutyrate. By contrast, two patients with PDHD showed clinical improvement as dystonic crises and fatigability decreased under basal metabolic conditions. In one of the two PDHD children, 3-hydroxybutyrate has largely replaced the ketogenic diet, with the latter that is mostly resumed only during febrile illness. Positive direct effects on energy metabolism in PDHD patients were suggested by negative correlation between ketonemia and lactatemia (r3-hydroxybutyrate may be an adjuvant treatment to ketogenic diet in PDHD but not in GLUT1-DS under basal metabolic conditions. Nevertheless, ketogenic diet is still necessary in PDHD patients during febrile illness.
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- 2017
5. Liens métaboliques entre la codéine et la morphine
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K.-H. Le Quan Sang, M. Levacher, and J.-C. Thalabard
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Gynecology ,medicine.medical_specialty ,Chemistry ,Medical screening ,medicine ,Orthopedics and Sports Medicine - Abstract
Resume Introduction. – La codeine est un medicament de la famille des opiaces naturels utilise comme antitussif et antalgique. Une des voies de metabolisation de la codeine dans l'organisme conduit a la formation de morphine ; cette biotransformation depend d'un systeme enzymatique complexe appartenant aux cytochromes P450. Synthese des faits. – Cette voie metabolique est soumise a une grande variabilite interindividuelle. Schematiquement, si l'on considere la capacite de metabolisation, la population generale est divisee en trois categories : metaboliseurs faibles, normaux et forts. Le polymorphisme genetique est la principale cause de cette heterogeneite. D'autres facteurs interviennent tels que l'etat de sante et les conditions environnementales. Conclusion. – Cette notion de variabilite est importante pour l'interpretation des tests de depistage s'appuyant sur des mesures urinaires de codeine et de morphine.
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- 2005
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6. Épidémiologie de la fibrodysplasie ossifiante progressive (FOP) en France, croisement de deux bases de données
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D. Lapidus, Amélie Ruel, K.-H. Le Quan Sang, Paul Landais, Stéphane Bouée, Claude Messiaen, Viviane Jeanbat, V. Cormier-Daire, C. Michot, Geneviève Baujat, and Rémy Choquet
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Epidemiology ,Public Health, Environmental and Occupational Health - Abstract
Introduction La fibrodysplasie ossifiante progressive (FOP) est une affection autosomique dominante rare, caracterisee par l’association d’anomalies congenitales des extremites et la survenue d’episodes successifs et cumulatifs d’ossifications musculaires irreversibles, conduisant a une ankylose progressive de l’axe vertebral et des membres. Objectifs La prevalence de la FOP est mal connue, evaluee de facon variable par deux etudes a 0,36 et 0,61 par million d’habitants. L’objectif de ce travail est d’estimer la prevalence a partir de deux systemes de collecte de donnees nationaux complementaires en France : donnees provenant soit de registres (CEMARA et MOC) soit medico-administratives (PMSI) afin notamment d’evaluer les patients non presents dans les registres. Methodes Cette etude a ete realisee a partir du croisement de CEMARA, base de donnees des centres maladies rares, existant depuis 2007 (integrant les patients FOP du registre local du centre de reference MOC etablit en 1990, apres accord des patients et des professionnels les prenant en charge) et du PMSI, base du programme de medicalisation des systemes d’information (donnees de 2006 a 2012). La date choisie pour l’estimation de la prevalence etait le 1er janvier 2012. Les patients decedes avant cette date ont ete exclus de l’etude. Resultats Les resultats preliminaires sont presentes ci-dessous. Les resultats du croisement des deux bases ne seront analyses qu’apres accord de la CNIL en attente. CEMARA et registre du CR MOC : au 01/01/2012, 85 patients vivants sont identifies FOP dans CEMARA et resident en France. Pour 63, le diagnostic avait ete confirme a cette date, 10 avaient deja des symptomes mais sans diagnostic confirme. Pour le reste (12), ces donnees sont manquantes. La prevalence est donc de 1,3 cas par million. Parmi ces 85 patients, 52 % sont des hommes, l’âge moyen est de 29 ans, 44 % ont moins de 20 ans, 48 % entre 20 et 60 ans et 8 % plus de 60 ans. PMSI : au 01/01/2012, 242 patients sont identifies dans le PMSI comme ayant ete hospitalises avec un code diagnostique CIM10 de FOP avant cette date et non decedes a cette date. La prevalence estimee est de 3,7 par million. Il est probable que certains de ces patients aient eu ce code diagnostique par exces. Ce point sera examine apres : (1) appariement des donnees avec la base CEMARA et (2) examen plus precis des donnees issues du PMSI sur ces hospitalisations (autres diagnostics, hospitalisations ulterieures). Parmi ces 242 patients, 44 % sont des hommes, l’âge moyen est de 42 ans, 18 % ont moins de 20 ans, 60 % entre 20 et 60 ans et 22 % plus de 60 ans. Conclusion Cette etude preliminaire permet de montrer pour cette pathologie une prevalence superieure aux etudes anterieures. Elle montre la pertinence du reseau CEMARA ainsi que le potentiel d’exploitation couple aux donnees medico-administratives en France pour les maladies rares. L’etude d’appariement avec le PMSI permettra d’affiner la precision de l’etude qui se situera probablement au-dessus de 1,3 cas par million en France (soit 1/770 000 residents).
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- 2016
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7. Influence of SIN-1 on Platelet Ca2+ Handling in Patients with Suspected Coronary Artery Disease: Ex Vivo and In Vitro Studies
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Thuc Do Pham, C. Le Feuvre, Annie Brunet, Marie-Aude Devynck, Vacheron A, Jean-Philippe Metzger, and K.-H. Le Quan Sang
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Thapsigargin ,biology ,Superoxide ,business.industry ,Hematology ,Pharmacology ,Nitric oxide ,Superoxide dismutase ,chemistry.chemical_compound ,Thrombin ,chemistry ,In vivo ,Immunology ,medicine ,biology.protein ,Platelet ,business ,Ex vivo ,medicine.drug - Abstract
SummaryThe 3-morpholinosydnonimine (SIN-1) generates both nitric oxide (NO) and superoxide anion (O2−). It elicits dose-dependent vasodilation in vivo, in spite of the opposite effects of its breakdown products on vascular tone and platelet aggregation.This study was designed to investigate the influence of intravenous SIN-1 injection on platelet Ca2+ handling in patients undergoing coronary angiography. SIN-1 administration reduced cytosolic [Ca2+] in unstimulated platelets by decreasing Ca2+ influx. It attenuated Ca2+ mobilization from internal stores evoked by thrombin or thapsigargin. In vitro studies were used as an approach to investigate how simultaneous productions of NO and O2− from SIN-1 modify thrombin- or thapsigargin-induced platelet Ca2+ mobilization. Superoxide dismutase, the O2− scavenger, enhanced the capacity of SIN-1 to inhibit Ca2+ mobilization but catalase had no effect.This suggests that the effects of SIN-1 on platelet Ca2+ handling resemble those of NO, but are modulated by simultaneous O2− release, independently of H2O2 formation.
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- 2000
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8. Hypercholesterolemia Modulates the Effects of Nitrendipine on Blood Pressure and Platelet Function in Essential Hypertension
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M. M. Mazeaud, K. H. Le Quan Sang, C. Astarie, J. Levenson, A. Simon, and M. A. Devynck
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Pharmacology ,Cardiology and Cardiovascular Medicine - Published
- 1991
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9. Influence of SIN-1 on platelet Ca2+ handling in patients with suspected coronary artery disease: ex vivo and in vitro studies
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K H, Le Quan Sang, C, Le Feuvre, A, Brunet, T D, Pham, J P, Metzger, A, Vacheron, and M A, Devynck
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Blood Platelets ,Male ,Aspirin ,Superoxide Dismutase ,Thrombin ,Biological Transport ,Middle Aged ,Catalase ,Coronary Angiography ,Angina Pectoris ,Superoxides ,Molsidomine ,Injections, Intravenous ,Humans ,Thapsigargin ,Calcium ,Female ,Nitric Oxide Donors ,Calcium Signaling ,Platelet Aggregation Inhibitors - Abstract
The 3-morpholinosydnonimine (SIN-1) generates both nitric oxide (NO) and superoxide anion (O2-). It elicits dose-dependent vasodilation in vivo, in spite of the opposite effects of its breakdown products on vascular tone and platelet aggregation. This study was designed to investigate the influence of intravenous SIN-1 injection on platelet Ca2+ handling in patients undergoing coronary angiography. SIN-1 administration reduced cytosolic [Ca2+] in unstimulated platelets by decreasing Ca2+ influx. It attenuated Ca2+ mobilization from internal stores evoked by thrombin or thapsigargin. In vitro studies were used as an approach to investigate how simultaneous productions of NO and O2- from SIN-1 modify thrombin- or thapsigargin-induced platelet Ca2+ mobilization. Superoxide dismutase, the O2- scavenger, enhanced the capacity of SIN-1 to inhibit Ca2+ mobilization but catalase had no effect. This suggests that the effects of SIN-1 on platelet Ca2+ handling resemble those of NO, but are modulated by simultaneous O2- release, independently of H2O2 formation.
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- 2000
10. Platelet cytosolic calcium concentration, plasma lipids and hypertension
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K H, Le Quan Sang, J, Levenson, A, Simon, and M A, Devynck
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Blood Platelets ,Male ,Cytosol ,Hypertension ,Humans ,Blood Pressure ,Calcium ,Female ,Middle Aged ,Extracellular Space ,Lipids - Abstract
To study the relationship between high blood pressure and hyperlipidaemia and the cytosolic calcium concentration in unstimulated platelets, focusing on the effects of an alteration in membrane dynamics.Basal cytosolic calcium concentrations were determined in the presence and the absence of a significant calcium influx in platelets of 47 untreated hypertensive patients and 26 normotensive subjects. Membrane microviscosity was investigated by fluorescence depolarization of diphenylhexatriene and trimethylaminodiphenylhexatriene. To study the influence of plasma factors, unstimulated platelets were loaded in the presence of plasma with Quin-2, which forms a relatively strong intracellular calcium buffer. The cytosolic calcium concentration was then determined at two extracellular calcium concentrations (1 mmol/l and in the absence of a Ca2+ influx).Irrespective of the external calcium concentration, the cytosolic calcium concentration increased significantly with diastolic blood pressure (P = 0.026 in the presence and P = 0.003 in the absence of Ca2+ influx) and with plasma triacylglycerols (P = 0.03 and 0.001, respectively). Multiple regression analysis indicated that the cytosolic Ca+ concentration was independently related to these two factors [Ca2+ = 35 + (18.6 +/- 4.6). In triacylglycerols (mmol/l) + (0.45 +/- 0.15) mmHg diastolic blood pressure; P0.001]. The relationship between the cytosolic calcium concentration and diphenylhexatriene or trimethylaminodiphenylhexatriene anisotropies was not independent of blood pressure and plasma triacylglycerol levels.The present results confirm the link between blood pressure and the platelet cytosolic calcium concentration and indicate that plasma triacylglycerols directly or indirectly modulate the ex vivo efficacy of platelet calcium storage and/or extrusion mechanisms. They could facilitate cell stimulation.
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- 1995
11. Wall shear stress and erythrocyte membrane microviscosity in hypertensive patients
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K H, Le Quan Sang, M, Del Pino, J, Levenson, A, Simon, and M A, Devynck
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Male ,Membrane Fluidity ,Regional Blood Flow ,Viscosity ,Erythrocyte Membrane ,Hypertension ,Humans ,Female ,Fluorescence Polarization ,Arteries ,Endothelium, Vascular ,Middle Aged ,Biomechanical Phenomena - Published
- 1993
12. Platelet cytosolic free calcium concentration in primary hypertension
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K H, Le Quan Sang, P, Benlian, C, Kanawati, T, Montenay-Garestier, P, Meyer, and M A, Devynck
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Adult ,Blood Platelets ,Male ,Cytosol ,Rats, Inbred SHR ,Hypertension ,Animals ,Humans ,Calcium ,Female ,Middle Aged ,Rats, Inbred WKY ,Rats - Abstract
Cytosolic free Ca2+ ([Ca2+]i) concentrations were measured in platelets from hypertensive and normotensive man and rat with the fluorescent indicator Quin-2/AM, taking into account the signal of the free chelator. In the absence of added external Ca2+, no difference in [Ca2+]i was observed between platelets of hypertensive patients and those of normotensive subjects or between platelets of spontaneously hypertensive rats (SHR; Okamoto-Aoki strain) and those of normotensive Wistar-Kyoto (WKY) rats. In the presence of 0.5-1 mmol/l external Ca2+, [Ca2+]i was higher in patients with essential hypertension than in their normotensive controls (250 +/- 14 versus 198 +/- 10 nmol/l; n = 30 and 36, P0.01). In SHR, platelet [Ca2+]i was higher than in WKY rats but did not change with age and blood pressure. Removal of external K+ or addition of 10(-4) mol/l ouabain were used to inhibit the Na+K(+)-pump. Whereas an increase in [Ca2+]i was observed in platelets from normotensives in the absence of external K+ (273 +/- 29 versus 197 +/- 9 nmol/l; n = 6; P0.05), no significant change in [Ca2+]i was observed after ouabain treatment (220 +/- 2 versus 203 +/- 22 nmol/l, n = 8). These results suggest that primary hypertension is accompanied by a disequilibrium between cellular Ca2+ influx, storage and extrusion. Such a characteristic, if present in other excitable cells and in particular in vascular smooth muscle cells, may play a major role in the increase in peripheral resistance. However, the relationship between Na(+)-pump inhibition and the rise in the intracellular calcium remains unclear.
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- 1985
13. Changes in platelet free Ca2+ concentration after chronic digoxin treatment
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P. Kerth, K. H. Le Quan-Sang, Philippe Meyer, Marie-Gabrielle Pernollet, David-Dufilho M, Marie-Aude Devynck, and M. Frisk-Holmbert
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Adult ,Blood Platelets ,Male ,medicine.medical_specialty ,Digoxin ,chemistry.chemical_element ,Stimulation ,Calcium ,Ouabain ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,Platelet ,Na+/K+-ATPase ,Pharmacology ,Chemistry ,Sodium ,Cytosol ,Endocrinology ,Intracellular ,Mathematics ,medicine.drug - Abstract
Cell Na+ and Ca2+ concentrations control each other by various mechanisms. In excitable cells from various origins, Ca2+ extrusion from the cell and its entry are dependent for a large part on the activity of the Na+, Ca2+-countertransport system. Cytosolic free Ca2+ concentration is also controlled by the Na+-H+ exchange activity. To analyze the changes in cytosolic Ca2+ concentration accompanying the reduction of the membrane Na+ gradient, cytosolic free Ca2+ concentration ([Ca2+]i) was measured by fluorescent dyes in platelets and erythrocytes from healthy subjects, before and during digoxin treatment (0.25 mg/day for 6 days). [Ca2+]i was increased in platelets from 169 +/- 30 to 321 +/- 61 nmol/l (n = 7, P less than 0.02) and unchanged in erythrocytes (121 +/- 6 and 104 +/- 7 nmol/l). This increase in platelet [Ca2+]i was not accompanied by a change in serotonin content (5.43 +/- 0.67 vs 5.49 +/- 0.61 10(-7) mol per 10(11) cells) and could not be reproduced by in vitro addition of 10(-4) mol/l ouabain (198 +/- 33 vs 186 +/- 73 nmol/l). The enhanced [Ca2+]i in platelets is thus not a short-term consequence of a reduced membrane Na+ gradient, but reflects either the overload of intracellular Ca2+ stores or an enhanced in vivo stimulation by hormones or neurotransmitters.
- Published
- 1987
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