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Biomedical subjects

J Prost

Publications and source records attributed to J Prost.

At least 19 recordsLinked to original sources

Effect of aqueous extract of Ajuga iva supplementation on plasma lipid profile and tissue antioxidant status in rats fed a high-cholesterol diet.

The present study was designed to explore the possible antioxidant and hypolipidemic effects of the aqueous extract of Ajuga iva (0.5% in the diet) in rats fed a high-cholesterol (1%) diet (HCD). The results indicated that the HCD-Ai versus HCD treatment led to many changes in biochemical parameters. They showed a decrease of plasma total cholesterol (TC) and VLDL-cholesterol but an increase of HDL(2)-cholesterol. The triacylglycerol contents were reduced in plasma and in VLDL. The lipid peroxidation determined by TBARS was decreased by 75% in plasma. TBARS in liver, heart and kidneys were highly reduced excepted in the adipose tissue. Ajuga iva treatment enhanced superoxide dismutase activity in liver and kidney. Glutathione reductase activity was lowered in adipose tissue but increased in liver and in kidney. A significant increase was noted in glutathione peroxidase activity in liver, heart and kidney but a low value in adipose tissue was observed. In conclusion, the present study demonstrates that in addition to its potent TG and TC-lowering effects, Ajuga iva is effective in improving the antioxidant status by reducing lipid peroxidation in plasma and tissues and enhancing the antioxidant enzymes in rats fed high-cholesterol diet. Furthermore, Ajuga iva may reduce intestinal cholesterol absorption.

Ajuga↗

Contractility and retrograde flow in lamellipodium motion.

We present a phenomenological description of cell locomotion on a solid substrate. The material properties of the actin cytoskeleton in the lamellipodium are described by the constitutive equations of a viscous polar gel with intrinsic activity. The polymerization of the gel takes place in a localized region near the leading edge. Using a simple two-dimensional description, we calculate in the steady state the thickness profile of the lamellipodium which at the rear connects to the cell body; we also calculate the flow profiles and the forces exerted on the substrate. The cell velocity is estimated as a function of externally applied forces. Our description is consistent with experimentally observed properties of motile cells such as the existence of a retrograde flow in the lamellipodium and a dipolar force distribution exerted by the cell on the substrate.

Actins↗

Generic phase diagram of active polar films.

We study theoretically the phase diagram of compressible active polar gels such as the actin network of eukaryotic cells. Using generalized hydrodynamics equations, we perform a linear stability analysis of the uniform states in the case of an infinite bidimensional active gel to obtain the dynamic phase diagram of active polar films. We predict, in particular, modulated flowing phases and a macroscopic phase separation at high activity. This qualitatively accounts for experimental observations of various active systems, such as actomyosin gels, microtubules and kinesins in vitro solutions, or swimming bacterial colonies.

Actins↗

N-3 fatty acids modulate antioxidant status in diabetic rats and their macrosomic offspring.

OBJECTIVE: We investigated the role of dietary n-3 polyunsaturated fatty acids (n-3 PUFA) in the modulation of total antioxidant status in streptozotocin (STZ)-induced diabetic rats and their macrosomic offspring. DESIGN: Female wistar rats, fed on control diet or n-3 PUFA diet, were rendered diabetic by administration of five mild doses of STZ on day 5 and were killed on days 12 and 21 of gestation. The macrosomic (MAC) pups were killed at the age of 60 and 90 days. MEASUREMENTS: Lipid peroxidation was measured as the concentrations of plasma thiobarbituric acid reactive substances (TBARS), and the total antioxidant status was determined by measuring (i) plasma oxygen radical absorbance capacity (ORAC), (ii) plasma vitamin A, E and C concentrations, and (iii) antioxidant enzymes activities in erythrocytes. The plasma lipid concentrations and fatty acid composition were also determined. RESULTS: Diabetes increased plasma triglyceride and cholesterol concentrations, whereas macrosomia was associated with enhanced plasma cholesterol and triglyceride levels, which diminished by feeding n-3 PUFA diet. N-3 PUFA diet also reduced increased plasma TBARS and corrected the decreased ORAC values in diabetic rats and their macrosomic offspring. EPAX diet increased the diminished vitamin A levels in diabetic mothers and vitamin C concentrations in macrosomic pups. Also, this diet improved the decreased erythrocyte superoxide dismutase and glutathione peroxidase activities in diabetic and macrosomic animals. CONCLUSION: Diabetes and macrosomia were associated with altered lipid metabolism, antioxidant enzyme activities and vitamin concentrations. N-3 PUFA diet improved hyperlipidemia and restored antioxidant status in diabetic dams and MAC offspring.

Animals↗

Effects of N-acyl-2-hydroxymethyl aziridines on in vitro proliferative responses of human lymphocytes stimulated by mitogens.

Aziridines have been shown to possess marked immunotropic activity. The aim of this work was to study the in vitro effects of different concentrations of three novel aziridines, 2-hydroxy-methyl-1-(N-phtaloylglycyl) aziridine (aziridine 1), 2-hydroxy-methyl-1-(N-phtaloylalanyl) aziridine (aziridine 2) and 2-hydroxy-methyl-1-(N-phtaloylphenylalanyl) aziridine (aziridine 3), on the proliferative responses of human lymphocytes stimulated by mitogens (concanavalin A (Con A) and lipopolysaccharide (LPS)), and interleukin-2 (IL-2), interleukin-6 (IL-6) secretion. The results showed that aziridines 1 and 3 significantly stimulated the resting and Con A or LPS lymphocyte proliferation at concentrations between 1 micromol/l and 1 mmol/l, in a dose-dependent manner, the action of aziridine 3 being the highest. They also increased IL-2 and IL-6 secretion. However, aziridine 2 had no effect on the resting lymphocyte proliferation in the absence of mitogens, at any concentration used, reduced Con A-stimulated T lymphocyte proliferation and LPS- stimulated B lymphocyte proliferation in a dose dependent manner and diminished IL-2 and IL-6 production. None of the three aziridines affected cell viability. In conclusion, the three aziridines used in this study displayed immunomodulatory properties. Aziridines 1 and 3 are potentially immunostimulant while aziridine 2 is immunosuppressive and could be used to provide nonspecific cell-mediated immune responses.

Aziridines↗

Antioxidant status in alcohol-related diabetes mellitus in Beninese subjects.

In the present study, we investigated the antioxidant status in diabetes mellitus, related or not to alcohol consumption. A total of 38 type 1, 48 type 2 and 42 alcohol-related diabetic patients were selected. Total antioxidant status was assessed through the oxygen radical absorbance capacity of the plasma and the determination of enzymatic and non-enzymatic antioxidant molecules. Serum triglycerides, total cholesterol and HDL-cholesterol concentrations were determined and the lipid peroxydation was evaluated by measuring thiobarbituric acid reactive substances (TBARS) assay. Plasma total antioxidant capacity was more decreased in alcohol-related diabetes than that in type 1 and type 2 diabetes, regardless of the complications (retinopathy and renal failure). Plasma vitamin E concentrations were significantly decreased whereas those of vitamin C increased in all of the diabetic patients compared to the controls, irrespective to the complications. In addition, superoxide dismutase and glutathione peroxidase activities were reduced in all the patients (type 1, type 2 and alcohol-related), irrespective to the complications. Glutathione reductase activity was diminished in type 1 and alcohol-related, but not in type 2, diabetic patients. Glutathione (GSH) concentrations significantly decreased in all diabetic patients with a significant decrease in alcohol-related diabetic patients. Excessive alcohol consumption appears as an oxidative aggravating factor in diabetes mellitus. Besides, alcohol-related diabetes highly resembles to type 1 diabetes as far as the antioxidant parameters are concerned.

Adult↗

Motor proteins transporting cargos.

Processive motor proteins such as kinesin and myosin-V are enzymes that use the energy of ATP hydrolysis to travel along polar cytoskeletal filaments. One of the functions of these proteins is the transport of vesicles and protein complexes that are linked to the light chains of the motors. Modeling the light chain by a linear elastic spring, and using the two-state model for one- and two-headed molecular motors, we study the influence of thermal fluctuations of the cargo on the motion of the motor-cargo complex. We solve numerically the Fokker-Planck equations of motor motion, and find that the mean velocity of the motor-cargo complex decreases monotonously as the spring becomes softer. This effect is due to the random force of thermal fluctuations of the cargo disrupting the operation of the motor. Increasing the size (thus, the friction coefficient) of the cargo also decreases the velocity. Surprisingly, we find that for a given size of the cargo, the velocity has a maximum for a certain friction of the motor. We explain this effect by the interplay between the characteristic length of thermal fluctuations of the cargo on a spring, the motor diffusion length, and the filament period. Our results may be relevant for the interpretation of single-molecule experiments with molecular motors (bead assays), where the motor motion is observed by tracking of a bead attached to the motor.

Biological Transport, Active↗

Passive or active fluctuations in membranes containing proteins.

We have experimentally investigated the effect of a transmembrane protein, the Ca2+-ATPase, on shape fluctuations of giant vesicles. By using the micropipette method, we have measured a substantial renormalization of the bending modulus due to the presence of proteins in the membrane. Moreover, we have produced the first quantitative measurement of the active force dipole associated with the amplification of the fluctuations when the proteins are activated by adenosine 5'-triphosphate (ATP).

Biological Transport, Active↗

Generic theory of active polar gels: a paradigm for cytoskeletal dynamics.

We develop a general theory for active viscoelastic materials made of polar filaments. This theory is motivated by the dynamics of the cytoskeleton. The continuous consumption of a fuel leads to a non equilibrium state characterized by the generation of flows and stresses. Our theory can be applied to experiments in which cytoskeletal patterns are set in motion by active processes such as those which are at work in cells.

Cell Physiological Phenomena↗

Fish protein improves blood pressure but alters HDL2 and HDL3 composition and tissue lipoprotein lipase activities in spontaneously hypertensive rats.

The two-month effects of dietary fish protein and casein on VLDL, HDL(2) and HDL(3) compositions and hepatic lipase (HTGL) and tissue lipoprotein lipase (LPL) activities were examined in spontaneously hypertensive rats (SHR) at 4 wk of age. After 2 mo of experiment, the fish protein diet induced lower blood pressure (-14 %) as compared to casein. Liver triacylglycerol and total cholesterol concentrations were 1.37- and 1.71-fold lower in the fish protein group than in the casein group, respectively. Total cholesterol concentration in plasma was also diminished by fish protein (-21 %) and was reflected in HDL(2) fraction (-44 %). SHR fed the fish protein diet as compared with those fed casein, showed a significantly low HDL(3) particle number, as measured by diminished HDL(3) mass and apo A-I. The consumption of fish protein did not affect VLDL particle number, but significantly decreased VLDL-triacylglycerol (-32 %) and adipose tissue total lipid concentrations as compared to casein. This was accompanied by diminished HTGL and adipose tissue LPL activities (-10%, -91%, respectively). These data demonstrate that fish protein plays an antihypertensive role and reduces plasma and tissue lipid concentrations. Thus, a fish protein intake might be beneficial for patients with hypertension.

Animals↗

Asters, vortices, and rotating spirals in active gels of polar filaments.

We develop a general theory for active viscoelastic materials made of polar filaments. This theory is motivated by the dynamics of the cytoskeleton. The continuous consumption of a fuel generates a nonequilibrium state characterized by the generation of flows and stresses. Our theory applies to any polar system with internal energy consumption such as active chemical gels and cytoskeletal networks which are set in motion by active processes at work in cells.

Adenosine Triphosphate↗

Role of tensile stress in actin gels and a symmetry-breaking instability.

It has been observed experimentally that the actin gel grown from spherical beads coated with polymerization enzymes spontaneously breaks the symmetry of its spherical shape, and yields a "comet" pushing the bead forward. We propose a mechano-chemical coupling mechanism for the initialization of this symmetry breaking. Key assumptions are that the dissociation of the gel takes place mostly in the region of the external surface, and that the rates of the dissociation depend on the tensile stress in the gel. We analyze a simplified two-dimensional model with a circular substrate. Our analysis shows that the symmetric steady state is always unstable against the inhomogeneous modulation of the thickness of the gel layer, for any radius of the circular substrate. We argue that this model represents the essential feature of three-dimensional systems for a certain range of characteristic lengths of the modulation. The characteristic time of the symmetry-breaking process in our model depends linearly on the radius of curvature of the substrate surface, which is consistent with experimental results, using spherical latex beads as substrate. Our analysis of the symmetry-breaking phenomenon demonstrates aspects of mechano-chemical couplings that should be working in vivo as well as in vitro.

Actins↗

Membranes with rotating motors: microvortex assemblies.

We study collections of rotatory motors confined to 2-dimensional manifolds. The rotational motion induces a repulsive hydrodynamic interaction between motors leading to a non-trivial collective behavior. For high rotation speed, motors should arrange on a triangular lattice exhibiting crystalline order. At low speed, they form a disordered phase where diffusion is enhanced by velocity fluctuations. In confining geometries and under suitable boundary conditions, motor-generated flow might enhance left-right symmetry-breaking transport. All these effects should be experimentally observable for motors driven by external fields and for dipolar biological motors embedded into lipid membranes in a viscoelastic solvent.

Adenosine Triphosphatases↗

Refined contour analysis of giant unilamellar vesicles.

The fluctuation spectrum of giant unilamellar vesicles is measured using a high-resolution contour detection technique. An analysis at higher q vectors than previously achievable is now possible due to technical improvements of the experimental setup and of the detection algorithm. The global fluctuation spectrum is directly fitted to deduce the membrane tension and the bending modulus of lipid membranes. Moreover, we show that the planar analysis of fluctuations is valid for spherical objects, even at low wave vectors. Corrections due to the integration time of the video camera and to the section of a 3D object by the observation plane are introduced. A precise calculation of the error bars has been done in order to provide reliable error estimate. Eventually, using this technique, we have measured bending moduli for EPC, SOPC and SOPC: CHOL membranes confirming previously published values. An interesting application of this technique can be the measurement of the fluctuation spectra for non-equilibrium membranes, such as "active membranes".

Algorithms↗

Fluid membranes exchanging material with external reservoirs.

We investigate the dynamics of a single component fluid bilayer, which exchanges material with the surrounding fluid. We derive covariant equations of motion taking into account solvent permeation, exchange of lipids between solvent and the membrane and discuss the sources of noise in these equations. Different lipid concentrations on both sides of the membrane lead to a non-equilibrium state. We discuss steady states as well as shape instabilities which occur at a critical osmotic-pressure difference.

Biophysics↗

Antioxidant status and levels of different vitamins determined by high performance liquid chromatography in diabetic subjects with multiple complications.

Plasma vitamin A, C and E levels and erythrocyte antioxidant enzyme activities were investigated in type I and type II diabetic subjects with and without complications, i.e., hypertension, coronary artery disease and renal failure. Reverse phase HPLC was used to quantify vitamin A and E levels. We observed that the vitamin C levels were not significantly different between control and diabetic subjects. However, vitamin A and E levels were significantly lower in type I and type II diabetic subjects compared to controls. Superoxide dismutase (SOD) activity was significantly lower in type II, but not in type I, diabetic patients compared to controls. Interestingly, glutathione reductase and peroxidase activities were diminished in type I, but not in type II, diabetic subjects as compared to controls. Catalase activity was lower in both types of diabetic patients in comparison with their respective controls. Altogether these results suggest that diabetes mellitus may be associated with altered antioxidant status regardless to various complications.

Adult↗

Bidirectional cooperative motion of molecular motors.

Recently, in a beautiful set of experiments, it has been shown that a Ncd mutant, NK11, which lacks directionality in its individual motion, was able to exhibit a new kind of directed motion in motility assays (Endow, S. A. & Higuchi, H. (2000) Nature (London) 406, 913-916): the filaments keep a given velocity for a while and then suddenly move in the opposite direction with similar velocity. We show that these observations nicely illustrate the concept of dynamic transitions in motor collections introduced earlier in the case of an infinite number of motors. We investigate the experimentally relevant case of a finite number of motors both when directionality is present (kinesins, myosins, Ncd) and absent (NK11). Using a symmetric two-state model, we demonstrate that bidirectional motion is the signature of a dynamic transition that results from the collective behavior of many motors acting on the same filament. For motors exhibiting directional bias individually, an asymmetric two-state model is appropriate. In that case, dynamic transitions exist for motor collections in the presence of an external force. We give predictions for the dependence of motion on ATP concentration, external forces, and the number of motors involved. In particular, we show that the reversal time grows exponentially with the number of motors per filament.

Computer Simulation↗

Active membrane fluctuations studied by micropipet aspiration.

We present a detailed analysis of the micropipet experiments recently reported by J-B. Manneville et al., [Phys. Rev. Lett. 82, 4356 (1999)], including a derivation of the expected behavior of the membrane tension as a function of the areal strain in the case of an active membrane, i.e., containing a nonequilibrium noise source. We give a general expression, which takes into account the effect of active centers both directly on the membrane and on the embedding fluid dynamics, keeping track of the coupling between the density of active centers and the membrane curvature. The data of the micropipet experiments are well reproduced by our expressions. In particular, we show that a natural choice of the parameters quantifying the strength of the active noise explains both the large amplitude of the observed effects and its remarkable insensitivity to the active-center density in the investigated range.

Bacteriorhodopsins↗