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Biomedical subjects

J F Stoltz

Publications and source records attributed to J F Stoltz.

At least 19 recordsLinked to original sources
PubMed2000

[Leukocyte adhesion on a fibrinogen-coated surface under static conditions: experimentation and creation of a model].

The adhesion of polymorphonuclear leukocytes (PMNs) on the vascular endothelium is a complex process that occurs during different biological and pathological events and involves numerous molecules. The adhesion cascade is induced after PMN stimulation by various molecular or cellular signals. Fibrinogen is one of the substrates for CD11b/CD18 B2-integrins expressed at the PMN surface; fibrinogen-neutrophil binding is induced by inflammatory reactions. In order to understand this process, we have carried out studies on the basis of preliminary experiments on red blood cells and synthetic particles. The modelization of quiescent PMNs adhesion on a fibrinogen substrate was investigated with a sedimentation cell chamber. Two different physiological conditions were tested: the activated state of PMN by a synthetic pro-inflammatory activator (FMLP). The activated state of PMNs was both quantified by flow cytometry and controlled by fluorescence microscopy. The results suggest that quiescent neutrophils deposit in accordance with the ballistic deposition model. This random adsorption model differs from random sequential adsorption (RSA) in that the cells arriving at the surface are able to roll along cells previously adsorbed introducing the notion of gravitational attraction of cells. The preliminary results obtained with stimulated PMN do not allow to choose between one of this two deposition models. Nevertheless, the qualitative and quantitative effects of FMLP on neutrophils were demonstrated by modifications of adhesion molecules expression.

Antigens, CD↗
PubMed1999

Rheological behaviour of red blood cells suspended in hemoglobin solutions. In vitro study comparing dextran-benzene-tetra-carboxylate hemoglobin, stroma free hemoglobin and plasma expanders.

Circulating volume expansion for intentional hemodilution and/or resuscitation of hemorrhagic shock can be performed with hemoglobin-based oxygen carriers (HBOC) which, in addition to oxygen transport, have vasoactive effects through poorly documented mechanisms. Among these, the effects of HBOC on red blood cell (RBC) rheology are relatively unknown. The aim of the present in vitro study was to measure the rheological effects of human hemoglobin bound to benzene-tetracarboxylate substituted dextran (Dex-BTC-Hb) as an example of chemically modified hemoglobin. The viscosity was assessed with a capillary and a rotational viscometer for shear rates of 0.5-128 s-1. Erythrocyte aggregation was determined by analysis of the red light backscattered in a RBC suspension and with a rheoscope. The deformability was determined by the pressure-flow relationship of the RBC suspensions passed through polycarbonate filters. At hematocrit of 0.35 l/l and at low shear rates, the viscosity of RBC was higher in the presence of Dex-BTC-Hb as compared to free Hb, Dex-BTC, Dextran 40 (Plasmacair), modified fluid gelatin (MFG-Plasmion) or hydroxyethyl starch (HEA-Elohes). The effect on erythrocyte aggregation of Dex-BTC-Hb was greater than that of standard solutions, but close to that of MFG or HEA. There was no apparent change in RBC deformability. Dex-BTC-Hb, unlike free Hb, has a hyperaggregating effect on RBC, similar to that of some clinically used volume expanders. This hyperaggregating effect could influence the in vivo rheological behavior of substituted Hb by increasing shear stress.

Blood Substitutes↗
PubMed1999

[Vascular disease and cellular activation: exploration of cell adhesion phenotype by quantitative flow cytometry].

The pathogenesis of atheromatous and/or thrombotic vascular diseases involves rheological parameters, soluble mediators and cellular agents. The many studies that have tried to establish correlations between plasma factors, shear stress and the risk of ischemia have left some questions unanswered. Current exploration methods are now focusing on the determining role of cells. Activated cells express adhesion molecules on their membranes, which allow to communicate in a homo- or heterotypical manner. Quantifying adherence molecules on the surface of platelets, leukocytes and endothelial cells provides an assessment of the "adhesive phenotypical profile". Quantitative cytometry, using beads coated with a known amount of immunoglobulins as calibrators, is perfectly suited, through its multiple parameter analyses and the specificity provided by monoclonal antibodies, for the quantification of membrane antigens. Measuring the adhesive profile on the surface of cells that are implicated in vascular disease makes it possible to correlate that phenotype to the ischemic risk in such diversified pathologies or circumstances as intermittent angor, myocardial infarction, angioplasty, insulin-dependent diabetes or pre-eclampsia. In addition, that quantification permits monitoring the action of new therapeutical agents targeting adherence molecules.

Angioplasty, Balloon, Coronary↗
PubMed1999

Senescent erythrocytes: modification of rheologic properties, antigenic expression and interaction with monocytes.

Human erythrocytes have a well-defined lifespan of 120 days. Their eventual removal from circulation is a complex process affected by many cellular parameters, making them susceptible to sequestration in the spleen and other organs. The purpose of this study was to investigate putative changes in rheologic properties, antigenic expression and interaction with monocytes of senescent erythrocytes (SE). SE and young erythrocyte (YE) fractions were obtained by differential centrifugation from 20 healthy donor blood samples. Membrane rheomechanic properties (by diffractometric method), ABO and MN antigens reactivity and erythrophagocytosis by peripheral monocytes were investigated in each fractions. SE showed a little decrease in the deformability index and an increase of both membrane elastic modulus and surface viscosity. The studies performed indicate a decreased expression in the antigens of both blood group systems studied (p < 0.01) and an increased rate of erythrophagocytosis by monocytes in SE compared to YE (p < 0.01). The significant modifications in the biomechanic properties of senescent red blood cell membrane and the loss of antigenic expression could lead to physiological phagocytosis.

Antigens↗
PubMed1999

[Hemorheology and vascular endothelial cells].

The vascular endothelium is a biologically active monolayer of cells providing an interface between the blood flow and tissues. Vascular Endothelial Cells (VEC) have two functional states. The endothelium is normally anti-thrombotic and anti-adhesive to ensure blood fluidity. During aggressions, such as atherosclerosis, inflammation states, metabolic diseases (through chemical or mechanical stimuli), VEC can reverse its functions by expressing stored material or by slower involvement of previously are repressed genes. Endothelial cells have three types of anti-thrombotic properties: vaso regulating properties: VEC release vasomotor components, such as endothelin (vasoconstriction), prostacyclin and nitric oxide, (vasodilatation). Endothelial cells also have antithrombotic and hemostatic properties. They express proteoglycans on their surface, including some negative-charge, plasminogen, sulfate glycosaminoglycans (heparan-sulfate), and secrete plasminogen tissular activator (t-PA) and tissular factor inhibitor. One fundamental action of the endothelium in that area is the production and expression of thrombomodulin, a thrombin receptor. This function has a major anticoagulation effect, controlling continual thrombin generation at the sub-endothelium and blood cell interface. Moreover, endothelial cells show anti-adhesion properties. During cardio-vascular diseases, all of these properties may be reversed. Thus the VEC have a determinant role in hemodynamic control through these various metabolic activities, such as control of homeostasis, vascular tone, blood fluidity, coagulating properties, cellular adhesion. Otherwise, many studies have demonstrated that local blood flow conditions have a crucial role on the VEC properties (mechanoactivation and mechanotransduction concept). In conclusion, knowledge of all the properties of the endothelial cells and control of the phenomena which define their functions is a key element in understanding cardiovascular diseases.

Animals↗
PubMed1999

Hemorheology and vascular endothelial cells.

The vascular endothelium is a biologically active monolayer of cells provided an interface between blood and tissues. Vascular endothelial cells (ECs) have two functional states, which are allowed by their different properties: (i) vaso regulating properties: ECs releases vasomotor components, as endothelin (vaso constriction), prostacyclin and nitrite oxide (vaso dilatation); (ii) antithrombotic and hemostatic properties; and (iii) anti-adhesion properties. The endothelium is normally antithrombotic and anti-adhesive to ensure blood fluidity. During many cardio-vascular diseases, these properties may be reversed. Thus, the ECs have a determinant role in hemodynamic control through these various metabolic activities. Otherwise, many studies have demonstrated that local blood flow conditions have a crucial role on the EC properties (mechanotransduction concept). The knowledge of the properties of ECs and the control of the phenomena which define their functions is a key element in the cardiovascular diseases understanding.

Animals↗
PubMed1999

Elasticity and fracture strain of whole blood clots.

The measurement of clot elasticity and fracture strain is carried out using a rotational rheometer with a controlled stress system. The elasticity is quantified by a shear elastic modulus and fracture strain by a critical strain (deformation) when the clot begins to break up. The results indicate a decrease of elasticity and increase of fracture strain of the clot with increasing hematocrit. Moreover, the elastic modulus of the clot is not constant but increasing with deformation.

Blood Coagulation↗
PubMed1999

Development and evaluation of an automatic method for the study of platelet osmotic response.

Study of the osmotic resistance to hypotonic medium of platelets has often been suggested as a global test to assess the viability of these cells in transfusion or to study modification during haematological pathologies. A number of authors have analysed the behaviour of platelets in hypotonic media by a variety of methods (cell count, determinations of substances released, morphology, etc.), but most studies are currently based on the so-called "Hypotonic Shock Response" test (HSR). In this study, the authors describe a new automated and reproducible apparatus, called fragilimeter, using slow dialysis to assess platelet osmotic resistance. The variations in light transmission through a platelet suspension according to ionic strength are linked to the change in cellular volume and lysis and characterise the osmotic behaviour of the cells. The results revealed the good reproducibility and sensibility of the technique. This apparatus allows also the realisation of the "HSR" test.

Adult↗
PubMed1999

Influence of a calcium antagonist on blood rheology and arterial compliance in hypertension: comparison with a thiazide diuretic.

Beyond their effects on blood pressure, antihypertensive agents may produce additional effects on blood rheology and arterial compliance abnormalities which may play a role in the target organ damage. These effects may depend only on their specific pharmacological properties. We compared the effects of nitrendipine to hydrochlorothiazide in 33 mild to moderate hypertensives in a double blind parallel group trial. Blood rheology and radial artery diameter and compliance were measured at t=0 and t=2 months. Both drugs produced blood pressure lowering. Blood viscosity decreased in the nitrendipine group and increased in the hydrochlorothiazide patients. Red blood cells deformability increased only in the nitrendipine group. Radial artery diameter and compliance were not different between the two groups but there was a trend to an increase of the cross-sectional compliance in hydrochlorothiazide group and to a decrease in nitrendipine group. Our data show that a calcium antagonist (Nitrendipine) could improve rheological parameters.

Antihypertensive Agents↗
PubMed1999

Membrane fluidity and oxygen diffusion in cholesterol-enriched endothelial cells.

In this study, we measured the influence of cholesterol rigidification on oxygen permeability in human endothelial cell monolayer membranes (ECs). Cholesterol-induced membrane rigidification was assessed at different membrane depths by a fluorescence polarization method with diphenyl-hexatriene (DPH) and 1-(4-trimethylamino)-6-phenylhexatriene (TMA-DPH). Fluorescence quenching by oxygen was probed in preferentially labelled membrane with pyrene butyric acid (PyC4) and pyrene dodecanoic acid (PyC12), as shown with a 3D fluorescence microscope (CellScan System). With both probes the experiments revealed a decrease in oxygen diffusion as the cholesterol concentration increased in the medium culture (from 3.42 microM to 17.11 microM). We showed that very low concentrations of cholesterol (about 1000 times below normal value, 6.2 mM) particularly decrease oxygen levels or diffusion rate in the middle region of the membrane. In conclusion, these findings prove in a direct manner that cholesterol significantly affect the endothelial barrier function and molecular oxygen transfer to underlying tissues. Risk factors (cholesterol) directly would contribute to tissue ischemia.

Biological Transport↗
PubMed1999

Measurement of erythrocyte deformability by two laser diffraction methods.

The aim of this work is to study the deformability of red blood cells (RBC) by two laser diffraction methods: the Laser-assisted Optical Rotational Cell Analyser (LORCA, Mechatronics, Amsterdam, Netherlands) and a Shear Stress Diffractometer (RHEODYN SSD, Myrenne, Roetgen, Germany). Experiments were carried out on 46 healthy human subjects. The elongation index EI of normal and hardened RBCs (obtained by heating blood at 49 degrees C or by incubating RBCs in solutions of diamide) was measured. The results showed that the standard deviations of the experimental data for normal RBCs were relatively small, especially at high shear stresses (more than 3.0 Pa), but higher than those reported before. Some correlations between the results given by the two instruments were also found. It should be noted that for hardened RBCs, the standard deviations of the measurements were important compared with the mean values in the two instruments.

Adult↗
PubMed1999

Comparison of three optical methods to study erythrocyte aggregation.

The aim of this work was to evaluate three optical methods designed to determine erythrocyte aggregation: Erythroaggregometer (EA; Regulest, France), Laser-assisted Optical Rotational Cell Analyzer (LORCA; Mechatronics, Netherlands) and Fully Automatic Erythrocyte Aggregometer (FAEA; Myrenne, GmbH, Germany). Blood samples were taken from fifty donors (26 males and 24 females). The aggregation of normal red blood cell (RBC) and RBCs suspended in three normo- and hyperaggregating suspending media was studied. The results revealed some significant correlations between parameters measured by these instruments, in particular, between the indexes of aggregation of EA and LORCA. Further, RBC aggregation of multiple myeloma patients was also studied and a hyper erythrocyte aggregation state was found by EA and LORCA.

Adult↗
PubMed1999

Modelisation of leukocyte adhesion on a fibrinogen coated surface in static conditions.

The adhesion of polymorphonuclear leukocytes (PMNs) on the vascular endothelium is a complex process that occurs during biological and pathological events and involves a large family of molecules. This phenomenom could be approached by a modelisation study of the adhesion of PMNs on a biological substrate, fibrinogen. Two different physiological conditions were tested such as the activated state of PMNs with a synthetic pro-inflammatory activator (N-Formyl-Methionyl-Leucyl-Phenylalanine, FMLP). The activated state of PMNs was both quantified by flow cytometry and controlled by fluorescence microscopy. The results suggest that quiescent PMNs deposit in accordance with the ballistic deposition model. The preliminary results obtained with FMLP-stimulated PMNs show a different deposit process compared to quiescent PMNs but do not allow to determine exactly a deposition model.

Activated-Leukocyte Cell Adhesion Molecule↗
PubMed1998

[New automatic test for the study of platelet response to variations in osmotic pressure: application in the evaluation of the viability of platelet concentrates].

Studying the osmotic resistance or swelling of platelets has often been suggested as a global test to assess the viability of those cells. A number of authors have also analysed the behaviour of platelets in hypotonic media by a variety of complementary methods (cell count, morphology, determinations of substances released, photometric measurement of aggregation induced by aggregating agents, etc). Most studies are currently based on the so-called "osmotic shock response" test, which measures according to time the light transmitted through platelet-rich plasma (PRP) after dilution in distilled water. In this study, the authors describe a new automated and reproducible test using slow dialysis to assess platelet osmotic resistance. The "Fragilimeter", a device initially described by the authors to characterise RBC fragility, has been adapted to the study of platelet osmotic behaviour. The variations in light transmission through a platelet suspension according to NaCl concentration are linked to the change in cellular volume and lysis and characterise the viability of the cells. The results obtained with normal platelets revealed the good reproducibility of the technique. The osmotic resistance is evaluated for two parameters: anticoagulant (citrate, EDTA) and cellular concentration. The test was applied to quality control of stored platelet concentrates for transfusion, prepared with different cell separators.

Blood Platelets↗
PubMed1998

Shear stress abnormalities contribute to endothelial dysfunction in hypertension but not in type II diabetes.

BACKGROUND: The relative contribution of the various hemodynamic and metabolic mechanisms leading to endothelial dysfunction may be different in specific vascular diseases. Since shear stress is one of the main mechanical stimuli of endothelial cells, the aim of this study was to investigate its contribution to endothelial dysfunction in two distinct vascular diseases, hypertension and type II diabetes. SUBJECTS AND METHODS: We measured the radial artery diameter at baseline, after ischemic vasodilation and after nitroglycerin vasodilation in 16 untreated patients with high blood pressure, in 15 type II normotensive diabetic patients and in 17 healthy controls. Wall shear stress was evaluated by simultaneous measurements of whole blood viscosity and blood flow velocity. RESULTS: In diabetic patients, whole blood viscosity was significantly higher whereas wall shear stress was similar compared to controls. In hypertensive patients, whole blood viscosity was higher and wall shear stress was lower than in controls. Endothelium-dependent vasodilation was impaired in both hypertensive and diabetic patients (P < 0.01) after adjustment for age, sex, body mass index and postnitroglycerin vasodilation. When adjustments were made for maximal systolic shear stress, endothelium-dependent vasodilation remained lower in the diabetic patients (P < 0.01), but not in those with high blood pressure compared to controls. CONCLUSIONS: In hypertension, endothelium-dependent vasodilation is mainly due to a chronic decrease in shear stress (the most important physiological stimulus of the endothelial cells) with no major intrinsic endothelial cell dysfunction. In contrast, in diabetics, the lower endothelium-dependent vasodilation was not the result of an altered shear stress.

Adult↗
PubMed1998

Calcium antagonists and thiazide diuretics have opposite effects on blood rheology and radial artery compliance in arterial hypertension: a randomized double-blind study.

In addition to their effects on blood pressure, antihypertensive agents may produce additional effects on blood rheology and arterial compliance abnormalities which may play a role in target-organ damage. However, these effects may depend only on the specific pharmacological properties of certain antihypertensive agents, and may be partly unrelated to blood pressure lowering action. We compared the effects of nitrendipine 20 mg once daily to hydrochlorothiazide 25 mg once daily in 33 mildly to moderately hypertensive and otherwise healthy patients, in a double blind parallel group trial. Blood rheology (blood fibrinogen and protein concentrations, hematocrit, plasma viscosity and whole blood viscosity at shear rates 0.2 to 128 s-1, erythrocyte deformability and aggregation) and radial artery diameter and compliance (Nius I + Finapres) were measured at baseline and after 2 months of treatment. Both drugs produced similar blood pressure lowering. Blood viscosity increased for all shear rates in the hydrochlorothiazide group and decreased in the nitrendipine treated group. Erythrocyte deformability increased in the nitrendipine but not in the thiazide group. Radial artery diameter and compliance were not different between the two groups but there was a trend towards an increase in cross-sectional compliance in the hydrochlorothiazide group and towards a decrease in the nitrendipine group. Our data show that, in mildly hypertensive patients, blood pressure control by nitrendipine produced more favourable effects on relevant rheological variables than hydrochlorothiazide. Radial artery compliance changes tended to be altered also in opposite directions by the two agents. The significance and the clinical relevance of these effects may require further investigations.

Antihypertensive Agents↗